Turkish vocabulary

Turkish vocabulary is the set of words within the Turkish language. The language widely uses agglutination and suffixes to form words from noun and verb stems. Besides native Turkic words, Turkish vocabulary is rich in loanwords from Arabic, Persian, French and other languages.
This article is a companion to Turkish grammar and contains some information that might be considered grammatical. The purpose of this article is mainly to show the use of some of the "yapım ekleri" "structural suffixes" of the Turkish language, as well as to give some of the structurally important words, like pronouns, determiners, postpositions, and conjunctions.
Origins.
"See also Turkish language#Vocabulary."
In the ninth century, Turks began to convert to Islam and to use the Arabic alphabet. When the Seljuk Turks overran Iran (Persia), they adopted for official and literary use the Persian language—which meanwhile had borrowed many Arabic words. Thus educated Turks had available for their use the vocabularies of three languages: Turkish, Arabic, and Persian.
When the Ottoman Empire arose out of the remains of the Selcuk Empire in Anatolia, its official language, "Osmanlıca" or Ottoman Turkish, became the only language to approach English in the size of its vocabulary (according to #Lewis). However, common people continued to use "kaba Türkçe" or "rough Turkish" which contained much fewer loanwords and which is the basis of the modern Turkish language.
With the advent of the Turkish Republic in 1923 came the attempt to unify the languages of the people and the administration, and to westernize the country. The modern Turkish alphabet, based on the Latin script, was introduced. Also, Arabic and Persian words were replaced, as possible, by:
Turkish words surviving in speech, obsolete Turkish words, new words formed regularly from the agglutinative resources of Turkish, thoroughly new words or formations. However, still a large portion of current Turkish words have Arabic or Persian origins.
Turkish has words borrowed from Greek due to the Ottoman Empire having conquered the Byzantine Empire. There are also borrowings from other European languages, or from the common technical vocabulary of Europe.
In the latter case, the borrowings are usually taken in their French pronunciation.
Origin of the words in Turkish vocabulary.
The 2005 edition of "Güncel Türkçe Sözlük", the official dictionary of the Turkish language published by Turkish Language Association, contains 104,481 words, of which about 86% are Turkish and 14% are of foreign origin. Among the most significant foreign contributors to Turkish vocabulary are Arabic, French, Persian, Italian, English and Greek.
Nouns.
Turkish nouns and pronouns have no grammatical gender (the same pronoun "o" means "he", "she" or "it"), but have six grammatical cases: nominative or absolute (used for the subject or an indefinite direct object), accusative (used for a definite direct object), dative (= to), locative (= in), ablative (= from), genitive (= of). There are two grammatical numbers, singular and plural.
Nouns from nouns and adjectives.
The suffix "-ci" attached to a noun denotes a person involved with what is named by the noun:
The suffix "-lik" attached to a noun or adjective denotes an abstraction, or an object involved with what is named by the noun:
Nouns from verbs.
The noun in "-im" denoting an instance of action was mentioned in the introduction to Turkish grammar.
For more examples on word derivations, see the "related article: List of replaced loanwords in Turkish".
Adjectives.
Classification of adjectives.
Adjectives can be distinguished as being
For an intensive form, the first consonant and vowel of a (descriptive) adjective can be reduplicated; a new consonant is added too, "m, p, r," or "s", but there is no simple rule for which one:
The determinative adjectives, or determiners, are an essential part of the language, although Turkish takes some of its determiners from Arabic and Persian.
Demonstrative adjectives.
These are also demonstrative pronouns. Used with plural nouns, these adjectives represent the English "those" and "these"; there is no such inflexion of adjectives in Turkish.
Numerical adjectives.
The cardinal numbers are built up in a regular way from the following:
Units follow multiples of ten; powers of ten come in descending order. For example:
The cardinals are generally not used alone, but a general word for a unit is used, such as:
Remembering that the plural suffix is not used when numbers are named, we have:
From the "cardinal" numbers, others can be derived with suffixes:
Indefinite adjectives.
The cardinal "bir" "one" can be used as an indefinite article.
Other so-called indefinite adjectives might be listed as follows:
Adjectives from nouns.
Added to a noun, "-li" or "-siz" indicates presence or absence, respectively, of what is named by the noun.
The suffix "-li" also indicates origin:
Finally, added to the verbal noun in "-me", the suffix "-li" creates the necessitative verb.
The native speaker may perceive "-meli" as an indivisible suffix denoting compulsion.
Added to a noun for a person, "-ce" makes an adjective.
Adverbs.
Adjectives can generally serve as adverbs:
The adjective might then be repeated, as noted earlier. A repeated noun also serves as an adverb:
The suffix "-ce" makes nouns and adjectives into adverbs. One source (Özkırımlı, p. 155) calls it the "benzerlik" ("similarity") or "görelik" (from "göre" "according to") "eki", considering it as another case-ending.
Adverbs of place include:
These can also be treated as adjectives and nouns (in particular, they can be given case-endings).
Also, the suffix "-re" can be added to the demonstrative pronouns "o", "bu", and "şu", as well as to the interrogative pronoun "ne", treated as a noun. The result has cases serving as adverbs of place:
Postpositions.
With genitive and absolute.
The following are used after the genitive pronouns "benim", "bizim", "senin", "sizin", "onun", and "kimin", and after the absolute case of other pronouns and nouns:
For example, a certain company may describe its soft drink as:
However, another company may say of itself:
Thus the label of postposition does not adequately describe "gibi"; Schaaik proposes calling it a predicate, because of its use in establishing similarity:
The particle "ile" can be both "comitative" and "instrumental"; it can also join the preceding word as a suffix. Examples:
With dative.
Used after nouns and pronouns in the dative case are:
With absolute.
The following postpositions are case-forms of nouns with the third-person possessional suffix; they can be understood as forming nominal compounds, "always indefinite", with the preceding words (see also Turkish grammar#Nouns):
Interjections.
Some samples include:
Conjunctions.
Some Turkish conjunctions are borrowed from Persian and Arabic.
Logical conjunction.
The "cumulative" sense of the English "A and B" can be expressed several ways:
For the "adversative" sense of "but" or "only", there are "ama" and "fakat" (both Arabic), also "yalnız" (which is also an adjective corresponding to "alone").
For emphasis: "hem A hem B" "both A and B".
Logical disjunction.
For the sense of English "(either)…or":
The pattern of the last two can be extended:
Logical non-disjunction.
 "NE ABD NE AB TAM BAĞIMSIZ DEMOKRATİK TÜRKİYE"
 "Neither USA nor EU: Fully Independent Democratic Turkey"
(slogan on placard at demonstration);
Implication.
Both "çünkü" and "eğer" are Persian; the latter is not generally needed, because the "conditional" form of the verb is available.
The conjunction "ki".
The Persian conjunction "ki" brings to Turkish the Indo-European style of relating ideas (#Lewis [XIII,15]):
 "Beklemesini istiyorum" "Her-waiting I-desire"; but
 "İstiyorum ki beklesin" "I-desire that he-wait."
Thus "ki" corresponds roughly to English "that", but with a broader sense:
 "Güneş batmıştı ki köye vardık" "The-sun had-set [when] that at-the-village we-arrived."
 "Kirazı yedim ki şeker gibi" "The-cherry I-ate [and found] that [it was] sugar like."
The following is from a newspaper:
 " "Vahdettin ne yazık ki haindi""
 "...Bu iki açıklamadan anlıyoruz ki
 Ecevit, Osmanlı Tarihi adlı bir kitap hazırlıyormuş...
 Vahdettin, Tevfik Paşa ve Londra Konferansı hakkındaki açıklamaları gösteriyor ki
 Sayın Ecevit, yakın tarihimizi ciddi olarak incelememiş,
 bu konudaki güvenilir araştırmaları ve sağlam belgeleri görmemiş...
 Diyor ki:
 "Benim şahsen çocukluğumdan beri dinlediğim şeyler var...""
 "...From these two accounts, we understand that
 Ecevit is preparing a book called Ottoman History...
 His accounts concerning Vahdettin, Tevfik Pasha and the London Conference show that
 Mr Ecevit has not seriously studied our recent history,
 has not seen trustworthy research and sound documentation on this subject...
 He says that:
 "'There are many things I heard personally from my childhood till today...'"
Verbs.
The verb-stem "temizle-" "make clean" is the adjective "temiz" "clean" with the suffix "-le-". Many verbs are formed from nouns or adjectives with "-le":
The suffix "-iş-" indicates reciprocal action, which is expressed in English by "each other" or "one another".
(But there are exceptions: "sevişmek" does not mean "to love one another" (from "sevmek" "to love") but rather "to make love with each other."
Many causative verbs are formed with "-dir-".
References.
Books of use in the writing of this article include:


Brook Bernacchi

Brook Antony Bernacchi (; 22 January 1922 – 22 September 1996) was a lawyer and politician in Hong Kong. He was the long-time chairman of the Reform Club of Hong Kong, the then quasi-opposition party in the colony and the longest serving elected officeholder in Hong Kong history, sitting on the Urban Council of Hong Kong, from 1952 to 1981, 1983 to 1986 and 1989 to 1995. He was well known for his efforts of pushing direct elections and political reform in Hong Kong.
Early life.
Bernacchi was born in London in 1922 and was educated in Westminster School and Cambridge University. He was called to the Bar in 1943 and joined the Royal Marines during the Second World War. He arrived in Hong Kong as part of the liberation forces in 1945 and joined the Hong Kong Bar Association in 1946 and was its chairman in 1963. He also became Queen's Counsel in 1960.
Political career.
In 1949, Bernacchi founded the Reform Club of Hong Kong, a political organisation consisting mostly of expatriates in the midst of the discussion on the Young Plan, a proposed constitutional reform put forward by Governor Mark Aitchison Young. He represented the club to run in the first Urban Council election in the post-war period, in 1952, and went on to hold the position for most of his public life.
The club, under Bernacchi's chairmanship, was involved in grassroots politics, calling for public housing for all, as thousands of refugees flooded into Hong Kong from the Communist uprising in China. He gained a reputation for outspokenness. For instance, he opposed Financial Secretary Sir Philip Haddon-Cave and his "positive non-interventionism", criticising him for cutting expenditure on the overdue housing programme. He also helped set up various groups including the Society for the Aid and Rehabilitation of Drug Abusers and the Discharged Prisoners Aid Society.
For his public services, he was awarded Officer of the Order of the British Empire (OBE) in 1965.
He and Elsie Elliott, another Reform Club Urban Councillor and a prominent social activist, were both questioned after the 1966 Kowloon Riots as they were indirectly involved in the riots by speaking for the protesters. He was also criticised for his dictatorial style of chairing the club. Elliott resigned from the club after receiving a stern rebuke from Bernacchi for her self-appointed delegation to London in May 1966.
Bernacchi showed rare support to the colonial government during the 1967 leftist riot and endorsed an outright crackdown.
Bernacchi had also been one of the leading voices for constitutional reform in Hong Kong since the 1950s. In 1978, he wrote to the Foreign Secretary David Owen that half of the Hong Kong population, 62 percent of those aged 18 to 34, "positively want a measure of elected representation" in the Legislative Council. He warned the British government that "if the voice of the people is not taken heed of now" there could be "disturbances". The warning received little attention from the government.
Seeing the increasing frustration with the limited franchise and the unwillingness of the government to introduce more elected offices, Bernacchi threatened to boycott the Urban Council elections in 1979. He later on stepped down in 1981, saying he wanted "no more to do with it" when the Government drew back from a pledge of universal suffrage. He also asked rhetorically, "how can one purport to represent nearly six million people in Hong Kong when you have been elected by only 6,000 voters?" He nevertheless led the club again in the following election, failing to win his seat, but was returned in 1983. In the 1986 election, Bernacchi again lost his seat, to Cheung Wai-ping, in Shau Kei Wan, before returning yet again in 1989.
In 1994, he became one of two foreigners appointed Hong Kong district affairs advisers to Beijing. As political reform and electoral politics developed rapidly in the last years of colonial rule, Bernacchi announced his retirement from the council in 1995, complaining that the council was becoming increasingly politicised.
Personal life and death.
He married Patricia Sheelagh Heath in 1970. He had three stepchildren, Robert Whitehead, SC (formerly vice-chairman of the Hong Kong Bar Association), Dr. Ian Whitehead and Mrs. Sarah Driver (née Whitehead).
He became the first Westerner to settle on Lantau Island in 1948. Having been inspired by the tea farms he visited in Burma during the Second World War, he set up the tea plantation at Ngong Ping next to the Po Lin Monastery. In 1973, he became a chairman of New Lantao Motor Bus Company Ltd. He was also one of the original founders of the Hong Kong Sea School, in Stanley, Hong Kong, which was set up to train young disadvantaged boys for a career in the Navy.
Bernacchi developed a brain tumour in 1961 which was diagnosed as benign but which left him with impaired use of his left arm and a limp. He died of brain tumour on 22 September 1996, aged 74. Prior to his death, he was the longest standing and most senior member of the Bar.


Agents of S.H.I.E.L.D. (season 3)

The third season of the American television series "Agents of S.H.I.E.L.D.", based on the Marvel Comics organization S.H.I.E.L.D., follows Phil Coulson and his team of S.H.I.E.L.D. agents and Inhumans as they face new threats to the world. It is set in the Marvel Cinematic Universe (MCU) and acknowledges the continuity of the franchise's films. The season was produced by ABC Studios, Marvel Television, and Mutant Enemy Productions, with Jed Whedon, Maurissa Tancharoen, and Jeffrey Bell serving as showrunners.
Clark Gregg reprises his role as Coulson from the film series, starring alongside the returning series regulars Ming-Na Wen, Brett Dalton, Chloe Bennet, Iain De Caestecker, Elizabeth Henstridge, Nick Blood, Adrianne Palicki. They are joined by Henry Simmons and Luke Mitchell who were promoted from recurring guest roles in the second season. The third season was ordered in May 2015, and filmed from that July to the following April. It takes inspiration from the "Secret Warriors" comic, combining it with the series' Inhuman and Hydra storylines, while paralleling the film "" (2016); connections to other MCU television series are also included in the season, as are characters from previous MCU media. Glenn Hetrick created prosthetics for the less-human looking Inhumans, Legacy Effects provided additional practical effects, and FuseFX returned to create the visual effects.
The first episode of the season premiered in Los Angeles on September 23, 2015, with the season, consisting of 22 episodes, airing on ABC from September 29, 2015, until May 17, 2016. The premiere was watched by 4.90 million viewers, higher than any episode of the entire second half of season two. Overall, the season had generally consistent ratings, and received positive reviews. Critics felt the series had 'hit its stride' with the season, and particularly praised the risky bottle episode "4,722 Hours", though the pacing of the season received criticism for trying to do too much at times. The series was renewed for a fourth season in March 2016.
Episodes.
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Production.
Development.
In March 2014, executive producer Jeffrey Bell stated at the "Agents of S.H.I.E.L.D." PaleyFest panel that the producers and the writers are able to read the screenplays for upcoming Marvel Cinematic Universe films to know where the universe is heading, which allowed them to form a general plan for the show through the end of a third season. The series was renewed for that third season on May 7, 2015. By April 2015, Marvel had been developing a spinoff series to accompany the season, starring Adrianne Palicki and Nick Blood, but ABC opted not to go ahead with it, with entertainment president Paul Lee saying, "We thought the right thing now is to leave [Palicki and Blood] on "S.H.I.E.L.D.", because "S.H.I.E.L.D." is so strong the moment".
However, a pilot for the spinoff was ordered in August 2015, with the series titled "Marvel's Most Wanted". Bell and fellow "Agents of S.H.I.E.L.D." executive producer Paul Zbyszewski developed the series, while working on Hunter and Morse's storyline for season three, preparing them to move over to the spin-off. Bell explained that it would set up "Marvel's Most Wanted" by defining exactly who the characters are, such as Hunter and his lack of loyalty to S.H.I.E.L.D. and to ideologies—"nothing specific about the show, it's just who Hunter is"—and that while the characters are "on "S.H.I.E.L.D.", we want to take advantage of who they are, and give the audience as much of their relationship with one another, and with other people, as possible. We are aware that there is a potential imminent end, and so they won't be neglected."
Hunter and Morse are written off the series in the episode "Parting Shot", both leaving S.H.I.E.L.D., as Palicki and Blood "physically had to go leave to shoot the pilot ... they had to stop being on "S.H.I.E.L.D." and get ready for the pilot and then shoot the pilot and all of that, so it didn't make sense for us to have all these episodes with them and then not have them in two or three episodes, and then go, "Oh, we were just over here," and then come back and go away again." On whether they could return to the series at some point, Bell said, "I can't answer that, but I can say it would be kind of cheating to make Mack cry like that only to buy it back—not that we haven't brought characters back from the dead. We want to earn stuff."
Writing.
In May 2015, Bell said that writing for the third season would begin the following month, with the story set six months after the events that concluded the second season. Bell stated that S.H.I.E.L.D. would be depicted as it was in the second season, underground with small "pockets" of S.H.I.E.L.D. around the world, as following the release of "" "we found we like our team ... as underdogs, as opposed to a giant, powerful, NSA organization that can do pretty much anything."
Regarding the characters that could appear in the season, Bell said in May 2015 that "The idea of some familiar faces with some new faces is something to look forward to. I also think finding some new Marvel characters to pull into the universe would be cool. Fans seem to respond when there are characters from the Marvel comics and Marvel Cinematic Universe." He later explained that the series has the opportunity to explore the Inhumans outside of the Royal Family (who are the major focus of the comics, television series and previously planned film). The season mentions the character Eden Fesi as an Inhuman, who is a mutant in the comics. The change was due to 20th Century Fox controlling the film and television rights to the majority of Marvel's X-Men and mutant characters.
When asked about possible hints made in the season two finale towards an adaptation of "Secret Warriors", Bell noted that the series does share the character Daisy Johnson with that comic, and "the idea of a team of powered people is something we've seen in the show ... I think there's a world down the road where we do our version." Elaborating on this and the series dealing with the many powered people introduced in season two, Bell said, "People seem to respond to powered people on the show and while it's not going to take over and become what the show's about, as a texture and flavor of the stories, we really enjoy that. The fact that Inhumans are now out there is something I think we need to investigate". He later clarified that characters would not have to be Inhuman to join the Secret Warriors, just powered, and that not just any powered character would be allowed to join, given that Daisy had to go through years of training on top of getting powers to join the team, and so similar rules would apply to other potential members. Executive producers Maurissa Tancharoen and Jed Whedon also discussed the Secret Warriors, the former cautioning "a very slow build" to the team, and the latter explaining, "We feel a duty to the Cinematic Universe to not hyper-accelerate how many people have powers ... We don't want it to be there's a thousand people with powers with a show that at its heart is about what it's like to not have powers in a world with powers."
In September 2015, Tancharoen stated the overall theme for the season explored with each character was them "trying to get back in touch with their humanity in a world where Inhumans are popping up," with Whedon adding that the nature of couples–some having broken up in previous episodes, some getting back together, and potential for new ones–would be explored. Later that month, Bell talked about some of the new character pairings in the season, saying "Putting Mack and Daisy together; putting Hunter and May together; putting Bobbi and Fitz together—suddenly you have all these different dynamics, all these different stories that you didn't have before." Tancharoen later highlighted the number of characters in the season compared to previous, stating that "There's more scale and scope, but at the same time, I think we're diving into each character's internal struggle a little bit more."
The second part of the season, which begins with episode 11, takes place three months after the events of episode 10. On the structure of the season and shifting the focus between the two parts, Bell stated it was the intent to follow the format from season two, by tying "a whole bunch of [interesting threads] but not all of them off by the midseason. And then we launch something exciting for the back half...the promise of more to come." Whedon added that "though we do break the season up, we feel that the season as a whole is one arc" and so the series would explore the same themes in the second half, "themes of what it means to be human and Inhuman. What does it mean to all these people when they have to live with their actions? Are they capable of the things their enemies are capable of?...What is the true nature of a person? Is everybody capable of everything if put in a terrible position? Or is there true good and a true evil?" The second half of the season sees the introduction of the comics' right-wing hate group the Watchdogs, depicted as radicals wishing to "eliminate the Inhumans", as well as a "cure" that can prevent terrigenisis in yet-to-transition Inhumans.
"Bouncing Back" opens with "a mysterious flash-forward to three months in the future, showing an unidentified S.H.I.E.L.D. agent seemingly dead in space." Tancharoen called it "the promise of something fairly ominous to come", and stated, "We will be uncovering things from the midseason opener all the way to the finale. We will slowly be discovering what that image is." She added that any "clues" would likely play out during present day sequences rather than further flash-forwards, such as when Daisy receives a vision of the flash-forward in "Spacetime", an episode where she learns that "she cannot change the outcome of these visions and the future is the future." Whedon discussed this idea, and that of the "theory behind the Inhumans that each one of them serves a purpose", saying, Inhumans "are made, they're not random. There's a lack of something that needs filling and an Inhuman will be created that fills that niche. It's an interesting concept we like playing with, and that plays into the idea of fate, which with our future visions, we're hitting pretty hard." On choosing Lincoln to be the one to die, which the executive producers knew going into the season when forming the arcs for Lincoln, Daisy, and Ward, Bell said he "earned it" adding that Lincoln comes to a point where he realizes what his purpose is, with Whedon noting that he understands that Daisy has a different purpose. Whedon continued that the decision was based on the fact that the series did not "want to be a body count show, but it is a real world with real stakes. What we had not done is the heroic death and the full-sacrifice death. This was a conscious decision. We also think that there’s a poetry in the fact that the person doing it doesn’t consider himself a hero. That’s the beauty of the moment—it’s not just for [Daisy], but it is, and it’s not just for him, but it is."
Discussing the season finale, Tancharoen stated, "This season, we've explored a lot of different themes: There's the notion of purpose. We also introduced an Inhuman who has a strong sense of faith. We talk a lot about destiny and all these things intertwine." Bennet likened the end of the season to "the end of the first book of S.H.I.E.L.D. This finale feels like the end of something bigger and the beginning of a whole new tone for the show." Whedon added, "We wanted to put a close to [Hive's] story. We knew going into this season what our plan was for both Ward and Hive. Our goal was to make it not just feel like victory—we like to get a victory and also a loss at the same time." On whether the Inhumans storyline would also be ending with the season, Whedon said, "We think of it as never closed. We like that we were able to open up that world and make Inhumans a permanent part of the universe. Now, we have a quick-fire way of introducing people with powers. It gives us a lot of leeway in our world, and it lets us explode the metaphors of what it is like to be different. We will never close that chapter." On making a six-month time jump at the end of "Ascension", Bell said that despite each character completing their arcs this season, "we still have a lot of plot. Emotionally, their arcs are done. What the jump lets you do is to do a reset ... It allows us to put down a lot of old plot and pick up a lot of new." Whedon added, "We’ve done it each season, so we just wanted to do it a little early ... we would’ve done [the time jump] in episode 1 next year but what we wanted to do was tease" things to come at the end of this season.
Casting.
All principal cast members from the first and second seasons (Clark Gregg as Phil Coulson, Ming-Na Wen as Melinda May, Brett Dalton as Grant Ward, Chloe Bennet as Daisy Johnson (no longer going by the name of "Skye"), Iain De Caestecker as Leo Fitz, Elizabeth Henstridge as Jemma Simmons, Nick Blood as Lance Hunter, and Adrianne Palicki as Bobbi Morse) return for the third season. In May 2015, Bell said that the writers would look to incorporate the character Lincoln Campbell into the season, as he was a "nice addition" to the second season, and that they were looking forward to exploring Mack's character in new ways during the third season following his role in the second-season finale. Luke Mitchell and Henry Simmons, who recurred as Lincoln and Mack, respectively, throughout the second season, were subsequently promoted to the principal cast for the third. During the season, Grant Ward is killed. His body is possessed by the parasitic Inhuman Hive, based on a creature from the "Secret Warriors" comic, with Dalton taking on that role. Also returning from earlier in the series are Daz Crawford as Kebo, Peter MacNicol as Elliot Randolph, Blair Underwood as Andrew Garner, Alicia Vela-Bailey as Alisha Whitley, Brian Patrick Wade as Carl Creel, Adrian Pasdar as Glenn Talbot, Raquel Gardner as Carla Talbot, Titus Welliver as Felix Blake, Reed Diamond as Daniel Whitehall, and Derek Phillips as O'Brien.
In July 2015, the Inhuman Lash, a villainous character from the comics, was confirmed to be appearing in the season, while Andrew Howard and Constance Zimmer were cast as Luther Banks and Rosalind Price, respectively, both recurring. In August 2015, Matthew Willig was revealed to be cast as Lash, while Juan Pablo Raba was announced as another new Inhuman, Joey Gutierrez. In October, Powers Boothe was announced in the recurring role of Gideon Malick, the previously unnamed World Security Council member that he portrayed in "The Avengers". The next month, Lash was revealed to be the Inhuman form of Andrew Garner, and Mark Dacascos was announced in the "heavily recurring" role of Giyera. Tyler Ritter appeared as Grant Ward's younger brother Thomas in December 2015. The character previously appeared as a boy through flashbacks in "The Well". By February 2016, Natalia Cordova-Buckley was cast as Elena "Yo-Yo" Rodriguez, a Secret Warrior from the comics. Axle Whitehead and John Hannah also recur as the Inhuman J.T. James / Hellfire and scientist Holden Radcliffe, respectively. Additionally, Alexander Wraith makes multiple appearances as the minor S.H.I.E.L.D. agent Anderson, while William Sadler reprises his role of President Matthew Ellis from "Iron Man 3".
Design.
The season introduces a new title graphic for the series, replacing the one that appeared for the first two seasons, as well as a new aircraft for the team called Zephyr One, designed by series visual effects vendor FuseFX. Glenn Hetrick again worked with the make-up and visual effects departments to design and create the more "unique"-looking Inhumans, such as Lash, after having worked on Raina during season two. Willig's Lash make-up initially took 6 hours to apply, but the make-up team was able to reduce the time to 4.5 hours. Before a new Inhuman character can be introduced, the cost of creating their powers must be weighed, with Bell saying, "Can we afford to produce this effect? Because every time last year Gordon [teleported] we went, 'Wow, that was [expensive].'" For the S.H.I.E.L.D. agents' costumes, series costume designer Ann Foley made sure to reflect the fact that they have "graduated from the ragtag group of soldiers and scientists to the more precise militaristic outfit they always imagined they were." As well, once Simmons returns from Maveth, her costumes did not feature any color, patterns, or prints, in order to reflect Simmons' emotional space.
Bennet cut her hair for the season, in order to further her character's transformation to the Daisy Johnson / Quake of the comics, while not cutting her hair as short as her comic counterpart. Bennet stated, "The comic book version of Daisy Johnson has very short, Miley Cyrus-esque hair. We wanted to stay true to the comic book character fans love; I wanted to please them but also make sure there was still some movement and length and sexiness in the hair." Bennet also received a new costume for the season, along with Quake's signature gauntlets. On the costume, Foley said, "It's about strength. She feels very empowered in it...I wanted to stay true to some of the designs I saw in the comics. In the style lines, I wanted to pay a little bit of a tribute to [Daisy's] tactical ability from last season, but we also incorporated the Quake symbol into her gauntlets and on the back of her suit." Legacy Effects created the gauntlets and utility belt, "out of flexible materials painted to look like metal" so as not to injure anyone during stunts.
After losing a hand at the end of the second season, Coulson receives a prosthetic replacement with "a few surprises hidden inside". Prop master Scott Bauer took a mold of Gregg's hand to build the prosthetic and was able to make the fingers bendable to depict Coulson holding objects. The hand evolves throughout the season, with a later iteration projecting an energy shield, inspired by a similar one used in the comics by Captain America. The energy shield was created by Cosa, one of the series' visual effects vendors.
Filming.
Production on the season began in late July 2015, in Culver City, California, and lasted until late April 2016. Location filming for the alien planet occurred in a work quarry in Simi Valley and in Northridge, Los Angeles near the Mojave Desert.
Music.
With the season reinventing the series again, composer Bear McCreary expanded the sound of the score "in a big way". In addition to introducing new themes for the characters of Lash and Rosalind Price, McCreary made some changes to the orchestra: "To represent Lash, I brought in larger percussion: merciless pounding taikos that I digitally compressed and distorted. This new, mangled percussion sound is horrific, and will become increasingly important as the season progresses." McCreary also brought in trombones "to get the scariest sound possible," which resulted in the recording space being reconfigured when they were recorded. For Price, her scenes with Coulson "give the series the feeling of a dense political thriller...I really leaned into that, musically. I introduce light acoustic percussion, mostly egg shakers, to give the pulsing synths a softer edge. And I used an acoustic piano to play the "Rosalind Theme" at key moments in her scenes...her music is meant to add intrigue and suspicion, and simultaneously allow us to have some fun with their witty banter." For "Maveth", McCreary used a 90-piece orchestra rather than the series' typical 50 or 70 players.
Marvel Cinematic Universe tie-ins.
On the season's potential for crossover with the rest of the MCU, Bell said in May 2015 that "I think [last] year worked really well—we got to be our own show and tell our own stories in the Marvel Cinematic Universe and do a nice hand off or a tie-in, but neither are incumbent upon the other to be a follow, and I think that's a great model for us. "Ant-Man" comes out this summer and will have come and gone before we air again in September, so whether there's anything vestigial from that or for [""] next season is to be determined. But we're in contact with the movie people and them with us, and any time we can put little easter eggs in, it's a lot of fun for die-hard fans." Bell also stated that there was a possibility of Hayley Atwell once again reprising her role as Peggy Carter in the season for an "Agent Carter" crossover, and after the series acknowledged the character's death in "Civil War", added, "Any time we can make a connection to her, whether in a flashback or dealing with what’s happening now, it makes the universe smaller."
In June 2015, it was revealed that the season would include the Secret Warriors team by introducing Inhuman characters inspired by the comic of the same name. The episode "Emancipation" is set in the aftermath of "Civil War", and deals with how the Secret Warriors and other Inhumans are affected by the Sokovia Accords, with some members of the S.H.I.E.L.D. team feeling "Inhumans should be registered and [others] who feel that's a first step to them being sequestered, imprisoned, exterminated." Wen noted that "The connection is there, but it’s also very tenuous at this point, because S.H.I.E.L.D. has become so isolated with what’s going on with the Avengers and them not knowing still that Coulson is alive." On how the themes of "Civil War" allowed the series to make more of a philosophical tie-in than with previous films, Whedon stated that "we do have people across the globe who have powers on our show and there would be varying reactions to that. A lot of fear, some excitement, some people wanting to use it for good, some people wanting to use it for evil. So, a lot of those same themes [from the film] will be addressed on our show." Bennet added, "we've been dealing with the bigger issues of "Civil War" on a smaller, more personal scale for a while now. It's been building. We've been having our own mini version of "Civil War"."
Additionally, the episode "Many Heads, One Tale" sees the season tie its Hydra and Inhuman storylines together, retconning the history of Hydra in the MCU, while the episode "Watchdogs" connects the series to several other MCU television shows: by featuring the chemical compound nitramene, which was developed by Howard Stark and seen in the "Agent Carter" episodes "Now is Not the End" and "Bridge and Tunnel"; by noting a gang war in Hell's Kitchen, as seen in the second season of "Daredevil"; and by referencing the company Damage Control, which was the focus of a potential MCU television series of the same name and later seen in '. Despite similarities between the final conversation between Daisy and Lincoln in "Ascension" and that of Steve Rogers and Carter in ', the executive producers did not mirror that scene intentionally, with Whedon stating "There’s something heartbreaking about not being able to be face-to-face with the person". "Ascension" also introduces the concept of Life Model Decoys.
Marketing.
To promote the inclusion of the Secret Warriors in the season, at San Diego Comic-Con International 2015, Marvel gave fans a chance to be a part of the team, with ambassadors roaming the convention to find the most dedicated fans and rewarding them with limited edition "Secret Warriors" pins. Fans with pins were then asked to post a photo of themselves wearing the pin to social media, for cast members of the series to select their favorites. A premiere was held for the season on September 23, 2015, at Pacific Theatres at The Grove in Los Angeles, where the first episode was shown. In early October, Marvel released a comedy video starring Dalton and Marvel Entertainment Chief Creative Officer Joe Quesada discussing a potential rebranding for Hydra, which was conceived and written by Dalton. On October 9, 2015, "A Wanted (Inhu)man" was screened at New York Comic Con, and on March 26, 2016, "Watchdogs" was screened at WonderCon.
Also at WonderCon, a poster based on the season was made available, with art by Mike McKone. It features Daisy, her pose an homage to a well-known "Secret Warriors" cover depicting the comic version of the character, with other main characters paired behind her (Coulson and Price, the latter because "she really was a big part of the first half of the season and...her death is the thing [that] drives Coulson", according to Bell; Fitz and Simmons; Hunter and Morse; May and Garner / Lash; and Mack and Elena Rodriguez). Lincoln is featured on his own, so as not to "take a super strong female character [Daisy] and reduce her to being a part of a relationship where she won't be fulfilled until she finds her man", as are Ward / Hive and Malick, the latter with the symbol of the former upon him: "We have told you who Ward's become, and Hive is the person that Malick is really in a relationship with. So the fact that reflection is on him or in him or around him is pretty potent," explained Bell.
Beginning with "The Singularity", the final episodes of the season were marketed as "Agents of S.H.I.E.L.D.: Fallen Agent", a "four-episode event". Marvel released clues as to who the Fallen Agent was online in the form of "sneak peek clips, artwork and more", leading up to the final reveal in the season finale. Marvel also released a poster for the event that recreated the cover of the "iconic" "The Amazing Spider-Man" #121 that served as the first issue of the story arc "The Night Gwen Stacy Died". The poster, created by Greg Land, also appeared as a "rare 1:1000" variant cover for "Civil War II" #0. Ahead of the final two episodes of the season, Marvel released a series of videos that "memorialized" each of the potential characters who could have been the Fallen Agent, with the Fallen Agent ultimately being Lincoln Campbell.
Release.
Broadcast.
The season began airing in the United States on ABC on September 29, 2015, and ran for 22 episodes. In Australia, the season aired on Fox8, rather than Seven Network with previous seasons, with a two-week delay from the U.S. airings. In the United Kingdom, the season moved to E4 after previously airing on Channel 4, and debuted on January 10, 2016.
Home media.
The season began streaming on Netflix on June 16, 2016, and was released on Blu-ray and DVD in Region 4 on March 1, 2017.
Reception.
Ratings.
The season averaged 5.52 million total viewers, including from DVR, ranking 85th among network series in the 2015–16 television season. It also had an average total 18-49 rating of 2.0, which was 47th.
Critical response.
The review aggregator website Rotten Tomatoes reports a 100% approval rating with an average score of 8.19/10, based on 22 reviews. The website's consensus reads, "Still evolving in its third season, "Marvel's Agents of S.H.I.E.L.D." further hits its stride with a blend of thrills, humor, and heart."
Based on the premiere, Merrill Barr of "Forbes" felt that the show "has grown up a lot since its first year, and with the start of season three, it's hard to imagine what complaints any fans could possibly still have. If you want overall continuity, you got it. If you want people with super powers going crazy, it's there. If you want an ensemble cast that brings the broadcast television corner of the MCU to life, then look no further. The point is, with the new season of "S.H.I.E.L.D.", it's everything one could ask from the show." Vulture's Scott Meslow stated that the premiere was "riddled with [many] visual signifiers, highlighting the ways "Agents of S.H.I.E.L.D." has gradually become sharper, sleeker, and more reliant on the bones of its comic-book source material."
Kevin Fitzpatrick at Screen Crush said that "Laws of Nature" "feels [like] the show's most confident, ambitious swing yet, its action-packed opening minutes a clear mission statement with an even more specific focus than Season 2." Brian Lowry, reviewing the episode for "Variety", said, "Television obviously can't compete with the budgets and action found in summer blockbusters...but it has an advantage in being able to explore characters. "Agents of S.H.I.E.L.D." obviously possesses a core audience drawn to those attributes, and showrunners Jed Whedon and Maurissa Tancharoen have admirably kept the plot moving ahead—engaging in larger serialized narratives—while grappling with the logistics of those ancillary considerations, which include plans for an "Inhumans" movie".
Eric Goldman of IGN scored the season a 7.9 out of 10, feeling it "had its up and downs, mixing in elements that worked (Daisy getting her Quake on, the Fitz and Simmons drama), elements we could have used more of (Secret Warriors!) and elements that just never felt right (Lincoln and his relationship with Daisy)." Goldman also felt that the first half of the season was "the stronger, more cohesive of the two halves" as it aired the episode "4,722 Hours" which Goldman called "the best hour of "Agents of S.H.I.E.L.D." to date." He criticized the pacing of the season, saying "some episodes felt a bit jumbled and could have benefited from slowing down a bit—or simply not trying to do so much at once. Sometimes it was just a question of including too many characters or storylines in single episodes, causing some scenarios to not have time to breathe or get the proper build up they might have with more character-focused episodes."
Analysis.
The season's connection to "Captain America: Civil War" of paralleling that film's themes and events was noted by critics.
Alex McCown, writing for "The A.V. Club", called the season's use of the Watchdogs as "the most topical and relevant to our real-world situation "Marvel's Agents of S.H.I.E.L.D." has ever gotten", comparing the group to Cliven Bundy and supporters of Donald Trump's 2016 presidential campaign, and feeling that "It's heartening to see the series laying this much groundwork in anticipation of mirroring the events of "Civil War". We've all talked about how the films affect the shows, but not vice versa. This narrative means "S.H.I.E.L.D." is taking full advantage of its medium in order to tell the story the upcoming Captain America film can't: A full and fraught exploration of the need to protect freedom and privacy, even for those with extraordinary abilities."
Fitzpatrick further discussed the "downright eerie parallel to current events" the Watchdogs brought to the series, saying that "if you stare at the news long enough it starts to mirror fiction, and boy if "Agents of S.H.I.E.L.D." didn't terrifyingly benefit from that [in "Watchdogs"]...Sometimes, anyone in need of someone to blame for their troubles can fall in with radicals." Fitzpatrick noted other MCU tie-ins in the same episode "never felt particularly labored, but rather lived-in with a world that stretches back to "Agent Carter"-era Stark tech, drops the odd "Daredevil" Easter Egg, and helps contextualize a world where heroes create country-dropping robots...A topical bent like tonight's "Watchdogs" made for a great angle to build up that world mentality without feeling particularly subservient to the movies."
Accolades.
"The Atlantic" named "4,722 Hours" one of the best television episodes of 2015.
! scope="row" rowspan="6" | 2016
References.
General references


Ross Davidson

William Russell "Ross" Davidson (25 August 1949 – 16 October 2006) was a Scottish actor best known for his role as Andy O'Brien in the BBC soap opera "EastEnders".
Career.
Davidson started his working life as a physical education teacher in Scotland in the early 1970s. He also played water polo at international level for Scotland. He left teaching to run a pub and disco in Glasgow, but furthered his ambitions to act by attending night classes.
He made his screen acting debut on television in "A Degree of Uncertainty" (1979), a BBC "Play for Today" set in a Scottish university, then appeared as a kilted dancer in "Stanley Baxter on Television" (1979). He also had small parts as a member of a mime troupe in "The Comedy of Errors" ("BBC Television Shakespeare", 1983) and a photographer in "Widows II" (1985), as well as appearing in the film "The Pirates of Penzance" (1983) and the Monty Python short "The Crimson Permanent Assurance" (1983), made to accompany the group's feature "The Meaning of Life". In Spain, the Netherlands and Germany he was seen in commercials for products ranging from chewing gum to beer.
In 1985 he became one of the original cast of the BBC's flagship soap opera "EastEnders". He played the altruistic nurse Andy O'Brien for 18 months, after which his screen alter-ego went down in history for being the first main character to be killed off, dying in a road accident in August 1986.
Just before he left "EastEnders" Davidson recorded a pop single, "Jigsaw Puzzle", that failed to chart. He then returned to acting in stage plays (he had previously appeared in "Guys and Dolls" at the National Theatre) and returned to the small-screen in 1987 as a television presenter. He presented the BBC lunchtime magazine show "Daytime Live" (1987–88) and the sports challenge series "Run the Gauntlet" (1989–90).
Davidson later returned to acting and appeared in the Channel 4 soap opera "Brookside" and in the Welsh soap "Pobol Y Cwm". He also played the role of Peter O'Dell in the Scottish soap "Take the High Road" for three years. He starred as Andy Morgan in the Channel 4 soap opera "Hollyoaks" from 1999 to 2002.
Personal life.
Davidson's first marriage was to a primary school teacher, but it ended within three years. He took his ex-wife's maiden name, Ross, as his stage name.
While he was working on "EastEnders" Davidson began a relationship with Shirley Cheriton, who played his on-screen girlfriend Debbie Wilkins. The couple separated after five years. He had a son with his second wife, Barbara Black, before they married in 2005. They lived together in the Essex resort of Frinton-on-Sea. Black had three children from her previous marriage.
Illness and death.
In February 2005 Davidson was diagnosed with a brain tumour, and swiftly underwent surgery. It was unsuccessful and a month later he was readmitted to the Oldchurch Hospital in Romford, where he was told that he had a glioblastoma Grade 4, the fastest-growing and most invasive form of brain tumour. In July 2005 Davidson went public with the news that his tumour was inoperable and that his life expectancy was 12–18 months. He died on 16 October 2006.


Ranolazine

Ranolazine, sold under the brand name Ranexa among others, is a medication used to treat heart related chest pain. Typically it is used together with other medications when those are insufficient. Benefits appear smaller in women than men. It is taken by mouth.
Common side effects include constipation, headache, nausea, and dizziness. Serious side effects may include QT prolongation. Use is not recommended in those with liver cirrhosis. How it works is not clear but may involve adenosine triphosphate.
Ranolazine was approved for medical use in the United States in 2006. In 2017, it was the 273rd most commonly prescribed medication in the United States, with more than one million prescriptions.
Medical uses.
Ranolazine is used to treat chronic angina. It may be used concomitantly with β blockers, nitrates, calcium channel blockers, antiplatelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers.
Its use is not recommended in Scotland as of 2019.
Contraindications.
Some contraindications for ranolazine are related to its metabolism and are described under Drug Interactions. Additionally, in clinical trials ranolazine slightly increased QT interval in some patients and the FDA label contains a warning for doctors to beware of this effect in their patients. The drug's effect on the QT interval is increased in the setting of liver dysfunction; thus it is contraindicated in persons with mild to severe liver disease.
Side effects.
The most common side effects are dizziness (11.5%) and constipation (10.9%). Other side effects include headache and nausea.
Drug interactions.
Ranolazine is metabolized mainly by the CYP3A enzyme. It also inhibits another metabolizing enzyme, cytochrome CYP2D6. For this reason, the doses of ranolazine and drugs that interact with those enzymes need to be adjusted when they are used by the same patient.
Ranolazine should not be used with drugs such as ketoconazole, clarithromycin, and nelfinavir that strongly inhibit CYP3A, nor with drugs that activate CYP3A, such as rifampin and phenobarbital.
For drugs that are moderate CYP3A inhibitors, such as diltiazem, verapamil, and erythromycin, the dose of ranolazine should be reduced.
Drugs that are metabolized by CYP2D6, such as tricyclic antidepressants, may need to be given at reduced doses when administered with ranolazine.
Mechanism of action.
Ranolazine inhibits persistent or late inward sodium current ("I"Na) in heart muscle in a variety of voltage-gated sodium channels. Inhibiting that current leads to reductions in intracellular calcium levels. This in turn leads to reduced tension in the heart wall, leading to reduced oxygen requirements for the muscle. The QT prolongation effect of ranolazine on the surface electrocardiogram is the result of inhibition of "I"Kr, which prolongs the ventricular action potential. Ranolazine also exhibits its effects on the delayed rectifier current (hERG/"I"Kr potassium channels), it readily stimulates myogenesis, it reduces a pro-oxidant inflammation/oxidative condition, and activates the calcium signaling pathway.
Ranolazine prolongs the action potential duration, with corresponding QT interval prolongation on electrocardiography, blocks the "I"Na current, and prevents calcium overload caused by the hyperactive "I"Na current, thus it stabilizes the membrane and reducing excitability.
History.
Syntex Inc. originally began developing ranolazine in 1985 and 61 studies were completed from then until 1994. Afterwards, Phase 2 studies were done however it was found that the formulation did not result in adequate plasma concentrations of drug. It is due to this that the sustained-release (SR) formulation of ranolazine was created.
Roche acquired Syntex in 1994 In 1996, CV Therapeutics licensed the North American and European rights to ranolazine from Syntex, a subsidiary of Roche, which had discovered the drug and had developed it through Phase II trials in angina. In 2006, CV Therapeutics acquired the remaining worldwide rights to ranolazine from Roche. In 2008 CV Therapeutics exclusively licensed rights for ranolazine in Europe and some other countries to Menarini.
In 2009, Gilead acquired CV Therapeutics. In 2013 Gilead expanded the partnership with Menarini to include additional countries, including those in Asia.
Society and culture.
Legal status.
Ranolazine was approved by the FDA in January 2006, for the treatment of patients with chronic angina as a second-line treatment in addition to other drugs. In 2007 the label was updated to make ranolazine a first-line treatment, alone or with other drugs. In April 2008 ranolazine was approved by the European EMEA for use in angina.
Commercial aspects.
Ranolazine is manufactured and sold as Ranexa by Gilead. According to a Gilead annual income statement, combined sales for Ranexa and another Gilead product, AmBisom, were $621 million for the fourth quarter of 2016.


Third occipital nerve

While under the Trapezius, the medial branch of the posterior division of the third cervical nerve gives off a branch called the third occipital nerve (also known as the least occipital nerve), which pierces the Trapezius and ends in the skin of the lower part of the back of the head.
It lies medial to the greater occipital nerve and communicates with it.


6-CAT

6-Chloro-2-aminotetralin (6-CAT) is a drug which acts as a selective serotonin releasing agent (SSRA) and is a putative entactogen in humans. It is a rigid analogue of "para"-chloroamphetamine (PCA).
According to Nichols "et al.", 6-CAT is a non-neurotoxic analog of PCA.


Lateral lemniscus

The lateral lemniscus is a tract of axons in the brainstem that carries information about sound from the cochlear nucleus to various brainstem nuclei and ultimately the contralateral inferior colliculus of the midbrain. Three distinct, primarily inhibitory, cellular groups are located interspersed within these fibers, and are thus named the nuclei of the lateral lemniscus.
Connections.
The brainstem nuclei include:
Fibers leaving these brainstem nuclei ascending to the inferior colliculus rejoin the lateral lemniscus. In that sense, this is not a 'lemniscus' in the true sense of the word (second order, decussated sensory axons), as there is third (and out of the lateral superior olive, fourth) order information coming out of some of these brainstem nuclei.
The lateral lemniscus is located where the cochlear nuclei and the pontine reticular formation (PRF) crossover. The PRF descends the reticulospinal tract where it innervates motor neurons and spinal interneurons. It is the main auditory tract in the brainstem that connects the superior olivary complex (SOC) with the inferior colliculus (IC). The dorsal cochlear nucleus (DCN) has input from the LL and output to the contralateral LL via the ipsilateral and contralateral Dorsal Acoustic Stria.
There are three small nuclei on each of the lateral lemnisci: the ventral, dorsal, and the intermediate. The two lemnisci communicate via the commissural fibers of Probst.
Nuclei of the lateral lemniscus.
The function of the complex of Nuclei of the lateral lemniscus is not known; however it has good temporal resolution compared to other cells higher than the cochlear nuclei and is sensitive to both timing and amplitude changes in sound. It is also involved in the acoustic startle reflex; the most likely region for this being the VNLL.
DNLL.
The cells of the DNLL respond best to bilateral inputs, and have onset and complexity tuned sustained responses. The nucleus is primarily GABAergic, and projects bilaterally to the inferior colliculus, and contralaterally to the DNLL, with different populations of cells projecting to each IC.
In rat, the DNLL has a prominent columnar organization. Nearly all neurons are stained for GABA, especially in the central part of the nucleus, and the remaining GABA negative cells are interspersed with the positive, and often stain for glycine. Two populations of GABA+ cells are visible: larger, lightly stained cells that project to the contralateral IC, and smaller, darker stained cells that project ipsilaterally. GABAergic axon terminals form dense groups surrounded by GABA-lemniscal fibers throughout the nucleus, and synapse on both somata and in the neuropil. Glycinergic axon terminals, on the other hand, are more finely localized, with the majority of recipient neurons located laterally in the nucleus.
INLL.
INLL also has little spontaneous activity and broad tuning curves. The temporal responses are significantly different from cells of the VNLL.
This structure is greatly hypertrophied in the rat, forming a prominent bulge on the surface of the brainstem. GAD, GABA, and Glycine staining reveals several distinct regions that are not evident in standard cytoarchitectural preparations. A modest number of GABA-stained neurons are arranged in small groups, generally in the center of the nucleus, whereas glycine-stained neurons are more common and widely dispersed, with regional concentrations in the dorsolateral and ventrolateral portions of the nucleus. Most GABA+ cells are gly+ as well.]
VNLL.
Sound in the contralateral ear leads to the strongest responses in the VNLL, which deals with some temporary processing. The VNLL may also be essential to the IC’s decoding of amplitude modulated sounds.
VNLL cells have little spontaneous activity, broad and moderately complex tuning curves; they have both phasic and tonic responses and are involved in temporal processing.
In rat, the VNLL is composed of two subdivisions, the ventral (columnar) and dorsal (non columnar) regions. The columnar region contains many glycine-positive (0 GABA+) neurons, whereas the dorsal region contains clusters of GABA+ neurons intermingled with gly+ cells, with some cells containing both.
Inputs and outputs to nuclei.
The table below shows that each of the nuclei have a complicated arrangement of ipsilateral and contralateral afferent inputs and outputs:


Myelin

Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be likened to an electrical wire (the axon) with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, each myelin sheath insulates the axon over a single long section and, in general, each axon comprises multiple long myelinated sections separated from each other by short myelin sheath-gaps called nodes of Ranvier.
Myelin is formed in the central nervous system (CNS; brain, spinal cord and optic nerve) by glial cells called oligodendrocytes and in the peripheral nervous system (PNS) by glial cells called Schwann cells. In the CNS, axons carry electrical signals from one nerve cell body to another. In the PNS, axons carry signals to muscles and glands or from sensory organs such as the skin. Each myelin sheath is formed by the concentric wrapping of an oligodendrocyte (CNS) or Schwann cell (PNS) process (a limb-like extension from the cell body) around the axon. Myelin reduces the capacitance of the axonal membrane. On a molecular level, in the internodes it increases the distance between extracellular and intracellular ions, reducing the accumulation of charges.
The discontinuous structure of the myelin sheath results in saltatory conduction, whereby the action potential "jumps" from one node of Ranvier, over a long myelinated stretch of the axon called the internode, before "recharging" at the next node of Ranvier, and so on, until it reaches the axon terminal. Nodes of Ranvier are the short (c. 1 micron) unmyelinated regions of the axon between adjacent long (c. 0.2 mm – >1 mm) myelinated internodes. Once it reaches the axon terminal, this electrical signal provokes the release of a chemical message or neurotransmitter that binds to receptors on the adjacent post-synaptic cell (e.g., nerve cell in the CNS or muscle cell in the PNS) at specialised regions called synapses.
This "insulating" role for myelin is essential for normal motor function (i.e. movement such as walking), sensory function (e.g. hearing, seeing or feeling the sensation of pain) and cognition (e.g. acquiring and recalling knowledge), as demonstrated by the consequences of disorders that affect it, such as the genetically determined leukodystrophies; the acquired inflammatory demyelinating disorder, multiple sclerosis; and the inflammatory demyelinating peripheral neuropathies. Due to its high prevalence, multiple sclerosis, which specifically affects the central nervous system (brain, spinal cord and optic nerve), is the best known disorder of myelin.
Development.
The process of generating myelin is called myelination or myelinogenesis. In the CNS, cells called oligodendrocyte precursor cells (OPCs; the precursors of oligodendrocytes) differentiate into mature oligodendrocytes, which form myelin. In humans, myelination begins early in the 3rd trimester, although only little myelin is present in either the CNS or the PNS at the time of birth. During infancy, myelination progresses rapidly, with increasing numbers of axons acquiring myelin sheaths. This corresponds with the development of cognitive and motor skills, including language comprehension, speech acquisition, crawling and walking. Myelination continues through adolescence and early adulthood and although largely complete at this time, myelin sheaths can be added in grey matter regions such as the cerebral cortex, throughout life.
Species distribution.
Myelin is considered a defining characteristic of the jawed vertebrates (gnathostomes), though axons are ensheathed by a type of cell, called glial cells, in invertebrates. These glial wraps are quite different from vertebrate compact myelin, formed, as indicated above, by concentric wrapping of the myelinating cell process multiple times around the axon. Myelin was first described in 1854 by Rudolf Virchow, although it was over a century later, following the development of electron microscopy, that its glial cell origin and its ultrastructure became apparent.
In vertebrates, not all axons are myelinated. For example, in the PNS, a large proportion of axons are unmyelinated. Instead, they are ensheathed by non-myelinating Schwann cells known as Remak SCs and arranged in Remak bundles. In the CNS, non-myelinated axons (or intermittently myelinated axons, meaning axons with long non-myelinated regions between myelinated segments) intermingle with myelinated ones and are entwined, at least partially, by the processes of another type of glial cell called the astrocyte.
Composition.
CNS myelin differs slightly in composition and configuration from PNS myelin, but both perform the same "insulating" function (see above). Being rich in lipid, myelin appears white, hence the name given to the "white matter" of the CNS. Both CNS white matter tracts (e.g. the optic nerve, corticospinal tract and corpus callosum) and PNS nerves (e.g. the sciatic nerve and the auditory nerve, which also appear white) each comprise thousands to millions of axons, largely aligned in parallel. Blood vessels provide the route for oxygen and energy substrates such as glucose to reach these fibre tracts, which also contain other cell types including astrocytes and microglia in the CNS and macrophages in the PNS.
In terms of total mass, myelin comprises approximately 40% water; the dry mass comprises between 60% and 75% lipid and between 15% and 25% protein. Protein content includes myelin basic protein (MBP), which is abundant in the CNS where it plays a critical, non-redundant role in formation of compact myelin; myelin oligodendrocyte glycoprotein (MOG), which is specific to the CNS; and proteolipid protein (PLP), which is the most abundant protein in CNS myelin, but only a minor component of PNS myelin. In the PNS, myelin protein zero (MPZ or P0) has a similar role to that of PLP in the CNS in that it is involved in holding together the multiple concentric layers of glial cell membrane that constitute the myelin sheath. The primary lipid of myelin is a glycolipid called galactocerebroside. The intertwining hydrocarbon chains of sphingomyelin strengthen the myelin sheath. Cholesterol is an essential lipid component of myelin, without which myelin fails to form.
Function.
The main purpose of myelin is to increase the speed at which electrical impulses propagate along the myelinated fiber. In unmyelinated fibers, electrical impulses (action potentials) travel as continuous waves, but, in myelinated fibers, they "hop" or propagate by saltatory conduction. The latter is markedly faster than the former, at least for axons over a certain diameter. Myelin decreases capacitance and increases electrical resistance across the axonal membrane (the axolemma). It has been suggested that myelin permits larger body size by maintaining agile communication between distant body parts.
Myelinated fibers lack voltage-gated sodium channels along the myelinated internodes, exposing them only at the nodes of Ranvier. Here, they are highly abundant and densely packed. Positively charged sodium ions can enter the axon through these voltage-gated channels, leading to depolarisation of the membrane potential at the node of Ranvier. The resting membrane potential is then rapidly restored due to positively charged potassium ions leaving the axon through potassium channels. The sodium ions inside the axon then diffuse rapidly through the axoplasm (axonal cytoplasm), to the adjacent myelinated internode and ultimately to the next (distal) node of Ranvier, triggering the opening of the voltage gated sodium channels and entry of sodium ions at this site. Although the sodium ions diffuse through the axoplasm rapidly, diffusion is decremental by nature, thus nodes of Ranvier have to be (relatively) closely spaced, to secure action potential propagation. The action potential "recharges" at consecutive nodes of Ranvier as the axolemmal membrane potential depolarises to approximately +35 mV. Along the myelinated internode, energy-dependent sodium/potassium pumps pump the sodium ions back out of the axon and potassium ions back into the axon to restore the balance of ions between the intracellular (inside the cell, i.e. axon in this case) and extracellular (outwith the cell) fluids.
Whilst the role of myelin as an "axonal insulator" is well-established, other functions of myelinating cells are less well known or only recently established. The myelinating cell "sculpts" the underlying axon by promoting the phosphorylation of neurofilaments, thus increasing the diameter or thickness of the axon at the internodal regions; helps cluster molecules on the axolemma (such as voltage-gated sodium channels) at the node of Ranvier; and modulates the transport of cytoskeletal structures and organelles such as mitochondria, along the axon. In 2012, evidence came to light to support a role for the myelinating cell in "feeding" the axon. In other words, the myelinating cell seems to act as a local "fueling station" for the axon, which uses a great deal of energy to restore the normal balance of ions between it and its environment, following the generation of action potentials.
When a peripheral fiber is severed, the myelin sheath provides a track along which regrowth can occur. However, the myelin layer does not ensure a perfect regeneration of the nerve fiber. Some regenerated nerve fibers do not find the correct muscle fibers, and some damaged motor neurons of the peripheral nervous system die without regrowth. Damage to the myelin sheath and nerve fiber is often associated with increased functional insufficiency.
Unmyelinated fibers and myelinated axons of the mammalian central nervous system do not regenerate.
Clinical significance.
Demyelination.
Demyelination is the loss of the myelin sheath insulating the nerves, and is the hallmark of some neurodegenerative autoimmune diseases, including multiple sclerosis, acute disseminated encephalomyelitis, neuromyelitis optica, transverse myelitis, chronic inflammatory demyelinating polyneuropathy, Guillain–Barré syndrome, central pontine myelinosis, inherited demyelinating diseases such as leukodystrophy, and Charcot–Marie–Tooth disease. Sufferers of pernicious anaemia can also suffer nerve damage if the condition is not diagnosed quickly. Subacute combined degeneration of spinal cord secondary to pernicious anaemia can lead to slight peripheral nerve damage to severe damage to the central nervous system, affecting speech, balance, and cognitive awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost, and the nerve eventually withers. A more serious case of myelin deterioration is called Canavan disease.
The immune system may play a role in demyelination associated with such diseases, including inflammation causing demyelination by overproduction of cytokines via upregulation of tumor necrosis factor or interferon.
Symptoms.
Demyelination results in diverse symptoms determined by the functions of the affected neurons. It disrupts signals between the brain and other parts of the body; symptoms differ from patient to patient, and have different presentations upon clinical observation and in laboratory studies.
Typical symptoms include blurriness in the central visual field that affects only one eye, may be accompanied by pain upon eye movement, double vision, loss of vision/hearing, odd sensation in legs, arms, chest, or face, such as tingling or numbness (neuropathy), weakness of arms or legs, cognitive disruption, including speech impairment and memory loss, heat sensitivity (symptoms worsen or reappear upon exposure to heat, such as a hot shower), loss of dexterity, difficulty coordinating movement or balance disorder, difficulty controlling bowel movements or urination, fatigue, and tinnitus.
Myelin repair.
Research to repair damaged myelin sheaths is ongoing. Techniques include surgically implanting oligodendrocyte precursor cells in the central nervous system and inducing myelin repair with certain antibodies. While results in mice have been encouraging (via stem cell transplantation), whether this technique can be effective in replacing myelin loss in humans is still unknown. Cholinergic treatments, such as acetylcholinesterase inhibitors (AChEIs), may have beneficial effects on myelination, myelin repair, and myelin integrity. Increasing cholinergic stimulation also may act through subtle trophic effects on brain developmental processes and particularly on oligodendrocytes and the lifelong myelination process they support. Increasing oligodendrocyte cholinergic stimulation, AChEIs, and other cholinergic treatments, such as nicotine, possibly could promote myelination during development and myelin repair in older age. Glycogen synthase kinase 3β inhibitors such as lithium chloride have been found to promote myelination in mice with damaged facial nerves. Cholesterol is a necessary nutrient for the myelin sheath, along with vitamin B12.
Dysmyelination.
Dysmyelination is characterized by a defective structure and function of myelin sheaths; unlike demyelination, it does not produce lesions. Such defective sheaths often arise from genetic mutations affecting the biosynthesis and formation of myelin. The shiverer mouse represents one animal model of dysmyelination. Human diseases where dysmyelination has been implicated include leukodystrophies (Pelizaeus–Merzbacher disease, Canavan disease, phenylketonuria) and schizophrenia.
Invertebrate myelin.
Functionally equivalent myelin-like sheaths are found in several invertebrate taxa including oligochaetes, penaeids, palaemonids, and calanoids. These myelin-like sheaths share several structural features with the sheaths found in vertebrates including multiplicity of membranes, condensation of membrane, and nodes. However, the nodes in vertebrates are annular; i.e. they encircle the axon. In contrast, nodes found in the sheaths of invertebrates are either annular or fenestrated; i.e. they are restricted to "spots". It is notable that the fastest recorded conduction speed (across both vertebrates and invertebrates) is found in the ensheathed axons of the Kuruma shrimp, an invertebrate, ranging between 90 and 200 m/s (cf. 100–120 m/s for the fastest myelinated vertebrate axon).


Basolateral amygdala

The basolateral amygdala (BLA), or basolateral complex, consists of the lateral, basal and accessory-basal nuclei of the amygdala. The lateral nuclei receives the majority of sensory information, which arrives directly from the temporal lobe structures, including the hippocampus and primary auditory cortex. The information is then processed by the basolateral complex and is sent as output to the central nucleus of the amygdala. This is how most emotional arousal is formed in mammals.
The basolateral amygdala and nucleus accumbens shell together mediate specific Pavlovian-instrumental transfer, a phenomenon in which a classically conditioned stimulus modifies operant behavior. One of the main functions of the basolateral complex is to stimulate the fear response. The fear system is intended to avoid pain or injury. For this reason the responses must be quick, and reflex-like. To achieve this, the “low-road” or a bottom-up process is used to generate a response to stimuli that are potentially hazardous. The stimulus reaches the thalamus, and information is passed to the lateral nucleus, then the basolateral system, and immediately to the central nucleus where a response is then formed. There is no conscious cognition involved in these responses. Other non-threatening stimuli are processed via the “high road” or a top-down form of processing. In this case, the stimulus input reaches the sensory cortex first, leading to more conscious involvement in the response. In immediately threatening situations, the fight-or-flight response is reflexive, and conscious thought processing doesn’t occur until later.
An important process that occurs in basolateral amygdala is consolidation of cued fear memory. One proposed molecular mechanism for this process is collaboration of M1-Muscarinic receptors, D5 receptors and beta-2 adrenergic receptors to redundantly activate phospholipase C, which inhibits the activity of KCNQ channels that conduct inhibitory M current. The neuron then becomes more excitable and the consolidation of memory is enhanced.
Distinct ensembles of neurons within the basolateral amygdala play a role in encoding associative memories and the response to painful stimuli. The ensemble activated in response to noxious stimuli are of particular interest for targeting treatments of chronic pain and cold allodynia. When neurons within this ensemble are silenced in a rodent model the affective component of pain is essentially erased, while a robust reflex response is maintained. This is thought to implicate the BLA in assigning a “pain tag” to valence information which may intrinsically encode that there is a priority to engage in pain-protective behaviors.
The amygdala has several different nuclei and internal pathways; the basolateral complex (or basolateral amygdala), the central nucleus, and the cortical nucleus are the most well-known. Each of these has a unique function and purpose within the amygdala.


Arthur Campbell (chemist)

Arthur Derek Campbell (27 May 1925 – 20 December 2020) was a New Zealand analytical chemist. He was a faculty member in the Department of Chemistry at the University of Otago from 1948 to 1988, becoming a professor emeritus on his retirement.
Early life and education.
Campbell was born in Waimate on 27 May 1925, the son of Mona Sevicke Campbell (née Jones) and David Brown Campbell. He was educated at Waimate High School, and then proceeded to study chemistry at the University of Otago, graduating Master of Science with second-class honours in 1948, and PhD in 1953. His doctoral thesis was titled "Some applications of acrylonitrile".
In 1950, Campbell married Ruth Florence Smith, and the couple went on to have three children.
Academic and research career.
Robinson was a faculty member in the Department of Chemistry at the University of Otago from 1948 to 1988. He was appointed as an assistant lecturer in 1948, rising to become a professor in 1971, and the Mellor Professor of Chemistry in 1983. He served as a member of the University Council from 1963 to 1971, dean of the Faculty of Science from 1980 to 1982, and head of the Department of Chemistry from 1983 to 1988. When he retired in 1988, he was conferred the title of professor emeritus.
Campbell's early research centred on carboxylic acid derivatives. However, he became interested in organic microanalysis, and developed many analytical procedures, and improved techniques for analysing perfluorinated organic compounds. Campbell served as chair of the Chemical Testing Registration Advisory Committee of the Testing Laboratory Registration Council of New Zealand from 1973 to 1985. Internationally, he was a Bureau Member of the International Union of Pure and Applied Chemistry from 1981 to 1989. The University of Otago's Campbell Microanalytical Laboratory is named in his honour.
Between 1979 and 1980, Campbell was president of the New Zealand Institute of Chemistry.
Later life and death.
Campbell's wife, Ruth, died in Dunedin on 18 March 2019. Campbell died in Dunedin on 20 December 2020.
Honours and awards.
In the 1989 Queen's Birthday Honours, Campbell was appointed an Officer of the Order of the British Empire, for services to science.


Hochbegabtenstudium

The Hochbegabtenstudium (, "College for the talented") is a programme in Germany that allows students of prerequisite intellectual ability (as shown on IQ tests) to attend college even if they do not hold the Abitur. The Hochbegabtenstudium is also called Schülerstudium ("college for school-students") because many of the students, who benefit from it are still enrolled in school, while they attend college.
Requirements.
A person wishing to do the Hochbegabtenstudium must be of above average intellectual ability and must as a rule have completed at least 10th grade. However some exceptions from that rule are made for very young students of superior intellectual ability, who are in a lower grade. In most cases a student wishing to participate in the programme must be at least 16 years old, however again exceptions from this rule are made for students of superior intellectual ability some of whom are only 13 or 14 when they enter college.
Notable examples.
In 2009 the case of Felix Dietlein made news. The young student of superior intellectual ability received his master's degree in mathematics (from the University of Cologne) one month before he graduated from his high school. He was only 18 at this time.


Pattie Coldwell

Pattie Coldwell (14 May 1952 – 17 October 2002) was a British TV presenter and journalist.
Born in Clitheroe, Lancashire, she attended Clitheroe Royal Grammar School for Girls before working as a secretary and starting in local television (Granada TV) as a reporter and presenter. She progressed to nationally networked programmes, such as "Nationwide", "Open Air", "Loose Women" and, on BBC Radio 4, "You and Yours". Her premature death resulted from a brain tumour at the age of 50; she had had breast cancer previously.
Her boyfriend for several years was the historian and broadcaster Michael Wood. She was married twice and had a daughter Dannie (born 1992) with her first husband, the presenter Tony Kerner.


Busbee

Michael James Ryan Busbee (June 18, 1976 – September 29, 2019), known professionally as busbee, was an American songwriter, record producer, publisher, record label executive, and multi-instrumentalist.
Early life.
Busbee was born in Walnut Creek, California, and grew up in the San Francisco Bay Area. He began playing piano when he was seven years old, and started playing jazz trombone in high school. Busbee marched with the World Class Drum Corps, Blue Devils.
He studied jazz at William Paterson University in Wayne, New Jersey, after receiving a scholarship to the school in 1995, but returned to the San Francisco Bay Area before graduating.
Career.
Busbee moved to Los Angeles in 2000 and started working at a music studio assisting rock producer Eric Valentine, and began learning to play more instruments, including guitar, bass, and drums. After working and assisting others in music studios for a while, he began working on his own as a songwriter, producer, mixer, writer, and engineer. He started working on many pop songs, with many artists who had been on reality singing competitions like "American Idol" and "The X Factor".
After five years of working in Los Angeles, he starting working in Nashville as well, at the recommendation of another writer. Musician and record producer Dann Huff then signed him to a publishing deal. Busbee has since written for and cowritten with a broad range of artists including Gwen Stefani, P!nk, Maren Morris, Timbaland featuring Katy Perry, Keith Urban, Jon Bellion, Kelly Clarkson, Florida Georgia Line, and Lady Antebellum. Busbee was nominated for a Grammy Award for Best Country Song in 2017 for his work on Maren Morris' debut single, "My Church".
In December 2018, Busbee started his own music label, Altadena, in Los Angeles in partnership with Warner Bros. Records, Warner Chappell Music, and Red Light Management.
Personal life.
Busbee was diagnosed with glioblastoma, a form of brain cancer, during the summer of 2019. He died on September 28th of that same year.


Topographic map (neuroanatomy)

A topographic map is the ordered projection of a sensory surface, like the retina or the skin, or an effector system, like the musculature, to one or more structures of the central nervous system. Topographic maps can be found in all sensory systems and in many motor systems.
Visual system.
The visual system refers to the part of the central nervous system that allows an organism to see. It interprets information from visible light to build a representation of the world. The ganglion cells of the retina project in an orderly fashion to the lateral geniculate nucleus of the thalamus and from there to the primary visual cortex(V1); adjacent spots on the retina are represented by adjacent neurons in the lateral geniculate nucleus and the primary visual cortex. The term for this pattern of projection is "topography". There are many types of topographic maps in the visual cortices, including retinotopic maps, occular dominance maps and orientation maps. Retinotopic maps are the easiest to understand in terms of topography. Retinotopic maps are those in which the image on the retina is maintained in the cortices (V1 and the LGN). In other words, if a specific region of the cortices was damaged that individual would then have a blind spot in the real world, they would not be able to see the bit of the world that corresponded to the retina damage. Orientation maps are also topographic. In these maps there are cells which have a preference to a certain orientation, the maximum firing rate of the cell will be achieved at that preference. As the orientation is moved away from the firing rate will drop. An orientation map is topographic because neighboring neural tissues have similar orientation preferences.
The term "retinotopic" refers to the maintenance of the particular order of afferent connections from the retina along the afferent pathway via sub-cortical structures to V1 and other cortical visual areas. The primary visual cortex (V1, Brodmann's area 17) is the first cortical area to receive visual input. The stria of Gennari – a set of heavily myelinated, horizontally projecting axons within the termination zone of lateral geniculate nucleus (LGN) input to V1 – provides an anatomical marker particular to V1.
Development.
According to the Chemoaffinity hypothesis, chemical labels are distributed in a graded fashion across the retina and tectum. This allows each retinal ganglion cell to recognize its proper termination site. Experiments with artificially created compound eyes in "Xenopus" demonstrate that not only the ganglion cells but also their axons carry these specificities. Axons must be able to communicate with each other to ensure that ones with the same positional tags innervate the same area of the superior colliculus.
Categories of retinotopic maps.
First-order representations are those in which adjacent points of the same hemifield always map to adjacent columns in the contralateral cortex. An example of this would be the map in primary visual cortex (V1).
Second-order representations, also known as a field discontinuity map, are maps that are organized such that it appears that a discontinuity has been introduced in either the visual field or the retina. The maps in V2 and other extrastriate cortex are second-order representations.
Auditory system.
The auditory system is the sensory system for hearing in which the brain interprets information from the frequency of sound waves, yielding the perception of tones. Sound waves enter the ear through the auditory canal. These waves arrive at the eardrum where the properties of the waves are transduced into vibrations. The vibrations travel through the bones of the inner ear to the cochlea. In the cochlea, the vibrations are transduced into electrical information through the firing of hair cells in the organ of Corti. The organ of Corti projects in an orderly fashion to structures in the brainstem (namely, the cochlear nuclei and the inferior colliculus), and from there to the medial geniculate nucleus of the thalamus and the primary auditory cortex. Adjacent sites on the organ of Corti, which are themselves selective for the sound frequency, are represented by adjacent neurons in the aforementioned CNS structures. This projection pattern has been termed tonotopy.
The tonotopic layout of sound information begins in the cochlea where the basilar membrane vibrates at different positions along its length depending upon the frequency of the sound. Higher frequency sounds are at the base of the cochlea, if it were unrolled, and low frequency sounds are at the apex. This arrangement is also found in the auditory cortex in the temporal lobe. In areas that are tonotopically organized, the frequency varies systematically from low to high along the surface of the cortex, but is relatively constant across cortical depth. The general image of topographic organization in animals is multiple tonotopic maps distributed over the surface of the cortex.
Somatosensory system.
The somatosensory system comprises a diverse range of receptors and processing centers to produce the perception of touch, temperature, proprioception, and nociception. Receptors are located throughout the body including the skin, epithelia, internal organs, skeletal muscles, bones, and joints. The cutaneous receptors of the skin project in an orderly fashion to the spinal cord, and from there, via different afferent pathways (dorsal column-medial lemniscus tract and spinothalamic tract), to the ventral posterior nucleus of the thalamus and the primary somatosensory cortex. Again, adjacent areas on the skin are represented by adjacent neurons in all aforementioned structures. This projection pattern has been termed somatotopy.
One common diagram of the somatotopic map is the cortical homunculus. This illustration is a fairly accurate representation of how much cortical area represents each body part or region. It also maps what part of the cortex represents each region of the body.
Motor system.
Unlike the topographic maps of the senses, the neurons of the motor cortex are efferent neurons that exit the brain instead of bringing information to the brain through afferent connections. The motor system is responsible for initiating voluntary or planned movements (reflexes are mediated at the spinal cord level, so movements that associated with a reflex are not initiated by the motor cortex). The activation from the motor cortex travels through Betz cells down the corticospinal tract through upper motor neurons, terminating at the anterior horn of the grey matter where lower motor neurons transmit the signal to peripheral motor neurons and, finally, the voluntary muscles.
Movements not requiring use of topographic maps.
There are several instances of movements that do not require the participation of topographic maps, or even the participation of the brain. One instance would be (as already stated) in some reflexes. Reflexes usually are mediated at the level of the spinal cord through reflex arcs. In humans, mono-, oligo-, and poly-synaptic reflex arcs, propriospinal interneuron systems, and internuncial gray matter neurons collectively participate continuously to produce spinal cord reflex that activates muscle.
The higher motor centers of octopuses (large brained invertebrates) are notable for organizing (unlike vertebrates) highly skilled movements without the use of somatotopic maps of their bodies.
Olfactory system.
The olfactory system is the sensory system used for olfaction, or the sense of smell. It detects volatile, airborne substances.
Most sensory systems spatially segregate afferent input from primary sensory neurons to construct a topographic map that defines the location of a sensory stimulus within the environment, as well as the quality of the stimulus itself. Unlike other sensory systems, the topography in the olfactory system is not dependent on spatial properties of the stimuli. Relieved of the requirement to map the position of an olfactory stimulus in space, the olfactory system employs spatial segregation of sensory input to encode the quality of an odorant.
The topographic map revealed in the olfactory system differs in quality from the orderly representation inherent in the retinotopic, tonotopic, or somatotopic sensory maps. Olfactory neurons differ from one another by the nature of the receptor that they possess. However, the olfactory sensory neurons to which olfactory bulb neurons are connected are also distributed across the receptor sheet (the olfactory epithelium) depending on their chemical preferences. Locations on the olfactory epithelium and the olfactory bulb are correlated so, as with other sensory systems, the topographic map in the brain is linked to the structure of the peripheral organ. This principle is called rhinotopy.
Individual olfactory sensory neurons express only one of the thousand receptor genes, such that neurons are functionally distinct. Cells expressing a given receptor in the olfactory epithelium are randomly dispersed within 1 of 4 broad zones. Sensory neurons extend a single unbranched axon to the olfactory bulb such that the projections from neurons expressing a specific receptor converge on 2 out of the 1800 glomeruli. The pattern of convergence is absolute and invariant in all individuals in a species. The bulb therefore provides a spatial map that identifies which of the numerous receptors have been activated within the sensory epithelium so that the quality of an olfactory stimulus is encoded by specific combination of glomeruli activated by a given odorant (combinatorial code).
While refinement of the bulbar topographic code relies on activity, the development occurs partly without apparent contribution from activity-dependent processes. Mice lacking the olfactory cyclic nucleotide-gated ion channel fail to exhibit odor-evoked electrophysiological responses in the sensory epithelium, but the pattern of convergence of like axons in the bulb is unaltered in these mutant mice, arguing strongly that olfactory experience is not necessary for the establishment or refinement of the topographic map.
These findings, however, do not exclude a role for activity-dependent processes in the maintenance or potential plasticity of the map after it is established. For example, neurons that do not express functional odorant receptors have been observed to have a significantly shorter half-life. Activity-dependent processes may therefore be essential for the survival of the olfactory neurons postnatally, and in that manner, may alter the input to individual glomeruli, altering the sensitivity to individual odors.
Gustatory system.
The gustatory system is the sensory system for taste. Like olfaction, taste requires a process of chemoreception. The receptors for taste are taste buds on the tongue. The tongue contains taste receptors, as well as mechanoreceptors. Afferents from taste receptors and mechanoreceptors of the tongue access different ascending systems in the brainstem. However, it is uncertain how these two sources of information are processed in cortex. The primary gustatory cortex (G) is located near the somatotopic region for the tongue (S1), in the insular cortex deep in the lateral fissure with the secondary taste areas in the opercula.
The peripheral taste system likely maintains a specific relationship between taste bud cells selectively responsive to one taste quality and the ganglion cells signaling that particular quality. This explains the response specificity of some individual taste nerve, particularly because sweet, amino acid, and bitter receptors are expressed in distinct populations of taste cells. Although anatomical evidence for such an exclusive relationship is lacking at the level of single receptor and ganglion cells, the relationship between single buds and their innervating ganglion cells is tractable neuroanatomically. In taste, attempts to identify a spatial representation of taste receptors or taste qualities have revealed only an indistinct functional topography in the brain. Nevertheless, taste ganglion cells must distribute peripheral fibers to particular receptor cell types and disseminate impulses centrally in a structurally organized manner.
Benefits.
For neurons, it is metabolically costly to make long connections, and the trade-off of connection distance is time. Thus, it is good design to group neurons together that are to be highly interconnected. Multiple topographic maps is a feature that is advantageous because it allows maps of different sizes that would accommodate varying levels of acuity and details in signals. A more detailed map has more neurons that would take up more area than a more global map, which would require fewer connections.
Techniques.
A variety of techniques have been used to establish the topographic maps in the brain. The existence of topographical maps was shown early by electrical stimulation of the cortex, tracing patterns of epileptic seizures, stimulation sequences, and impairments due to lesions. Details in the maps came later through microelectrode stimulation and recording techniques became commonly used in demonstrating somatotopic maps and later in the auditory and visual systems, both cortically and in subcortical structures such as the colliculi and geniculate nuclei of the thalamus. Single-cell recording, Transcranial magnetic stimulation(TMS), electrical stimulation of the cortex, and Functional magnetic resonance imaging(fMRI) are some of the techniques used to study maps in the brain. Many of the existing topographic maps have been further studied or refined using fMRI. For example, Hubel and Wiesel originally studied the retinotopic maps in the primary visual cortex using single-cell recording. Recently, however, imaging of the retinotopic map in the cortex and in sub-cortical areas, such as the lateral geniculate nucleus, have been improved using the fMRI technique.


RU-57073

RU-57073 is a nonsteroidal antiandrogen which was never marketed. It shows 163% of the affinity of testosterone for the androgen receptor and negligible affinity for other steroid hormone receptors.