hippocampus hippocampus the hippocampus (via latin from greek ἱππόκαμπος, 'seahorse') is a major component of the brain of humans and other vertebrates. humans and other mammals have two hippocampi, one in each side of the brain. the hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. the hippocampus is located in the allocortex, with neural projections into the neocortex in humans, as well as primates. the hippocampus, as the medial pallium, is a structure found in all vertebrates. in humans, it contains two main interlocking parts: the hippocampus proper (also called ammon's horn), and the dentate gyrus. hippocampushumans have two hippocampi, one in each hemisphere of the brain. they are located in the medial temporal lobes of the cerebrum. in this lateral view of the human brain, the frontal lobe is at the left, the occipital lobe at the right, and the temporal and parietal lobes have largely been removed to reveal one of the hippocampi underneath.hippocampus (lowest pink bulb)as part of the limbic systemdetailspart oftemporal lobeidentifierslatinhippocampusmeshd006624neuronames3157neurolex idbirnlex_721ta98a14.1.09.321ta25518fma275020anatomical terms of neuroanatomy in alzheimer's disease (and other forms of dementia), the hippocampus is one of the first regions of the brain to suffer damage; short-term memory loss and disorientation are included among the early symptoms. damage to the hippocampus can also result from oxygen starvation (hypoxia), encephalitis, or medial temporal lobe epilepsy. people with extensive, bilateral hippocampal damage may experience anterograde amnesia: the inability to form and retain new memories. since different neuronal cell types are neatly organized into layers in the hippocampus, it has frequently been used as a model system for studying neurophysiology. the form of neural plasticity known as long-term potentiation (ltp) was initially discovered to occur in the hippocampus and has often been studied in this structure. ltp is widely believed to be one of the main neural mechanisms by which memories are stored in the brain. in rodents as model organisms, the hippocampus has been studied extensively as part of a brain system responsible for spatial memory and navigation. many neurons in the rat and mouse hippocampus respond as place cells: that is, they fire bursts of action potentials when the animal passes through a specific part of its environment. hippocampal place cells interact extensively with head direction cells, whose activity acts as an inertial compass, and conjecturally with grid cells in the neighboring entorhinal cortex. name image 1: the human hippocampus and fornix (left) compared with a seahorse (right) the earliest description of the ridge running along the floor of the temporal horn of the lateral ventricle comes from the venetian anatomist julius caesar aranzi (1587), who likened it first to a silkworm and then to a seahorse (latin hippocampus, from greek ἱππόκαμπος, from ἵππος, 'horse' + κάμπος, 'sea monster'). the german anatomist duvernoy (1729), the first to illustrate the structure, also wavered between "seahorse" and "silkworm". "ram's horn" was proposed by the danish anatomist jacob winsløw in 1732; and a decade later his fellow parisian, the surgeon de garengeot, used cornu ammonis – horn of amun, the ancient egyptian god who was often represented as having a ram's head. another reference appeared with the term pes hippocampi, which may date back to diemerbroeck in 1672, introducing a comparison with the shape of the folded back forelimbs and webbed feet of the mythological hippocampus, a sea monster with a horse's forequarters and a fish's tail. the hippocampus was then described as pes hippocampi major, with an adjacent bulge in the occipital horn, described as the pes hippocampi minor and later renamed as the calcar avis. the renaming of the hippocampus as hippocampus major, and the calcar avis as hippocampus minor, has been attributed to félix vicq-d'azyr systematizing nomenclature of parts of the brain in 1786. mayer mistakenly used the term hippopotamus in 1779, and was followed by some other authors until karl friedrich burdach resolved this error in 1829. in 1861 the hippocampus minor became the center of a dispute over human evolution between thomas henry huxley and richard owen, satirized as the great hippocampus question. the term hippocampus minor fell from use in anatomy textbooks and was officially removed in the nomina anatomica of 1895. today, the structure is just called the hippocampus, with the term cornu ammonis (that is, 'ammon's horn') surviving in the names of the hippocampal subfields ca1-ca4. relation to limbic system the term limbic system was introduced in 1952 by paul maclean to describe the set of structures that line the deep edge of the cortex (latin limbus meaning border): these include the hippocampus, cingulate cortex, olfactory cortex, and amygdala. paul maclean later suggested that the limbic structures comprise the neural basis of emotion. the hippocampus is anatomically connected to parts of the brain that are involved with emotional behavior – the septum, the hypothalamic mammillary body, and the anterior nuclear complex in the thalamus, and is generally accepted to be part of the limbic system. anatomy main article: hippocampus anatomy image 2: cross-section of cerebral hemisphere showing structure and location of hippocampus image 3: coronal section of the brain of a macaque monkey, showing hippocampus (circled) the hippocampus can be seen as a ridge of gray matter tissue, elevating from the floor of each lateral ventricle in the region of the inferior or temporal horn. this ridge can also be seen as an inward fold of the archicortex into the medial temporal lobe. the hippocampus can only be seen in dissections as it is concealed by the parahippocampal gyrus. the cortex thins from six layers to the three or four layers that make up the hippocampus. the term hippocampal formation is used to refer to the hippocampus proper and its related parts. however, there is no consensus as to what parts are included. sometimes the hippocampus is said to include the dentate gyrus and the subiculum. some references include the dentate gyrus and the subiculum in the hippocampal formation, and others also include the presubiculum, parasubiculum, and entorhinal cortex. the neural layout and pathways within the hippocampal formation are very similar in all mammals. the hippocampus, including the dentate gyrus, has the shape of a curved tube, which has been compared to a seahorse, and to a horn of a ram, which after the ancient egyptian god often portrayed as such takes the name cornu ammonis. its abbreviation ca is used in naming the hippocampal subfields ca1, ca2, ca3, and ca4. it can be distinguished as an area where the cortex narrows into a single layer of densely packed pyramidal neurons, which curl into a tight u shape. one edge of the "u," – ca4, is embedded into the backward-facing, flexed dentate gyrus. the hippocampus is described as having an anterior and posterior part (in primates) or a ventral and dorsal part in other animals. both parts are of similar composition but belong to different neural circuits. in the rat, the two hippocampi resemble a pair of bananas, joined at the stems by the commissure of fornix (also called the hippocampal commissure). in primates, the part of the hippocampus at the bottom, near the base of the temporal lobe, is much broader than the part at the top. this means that in cross-section the hippocampus can show a number of different shapes, depending on the angle and location of the cut. in a cross-section of the hippocampus, including the dentate gyrus, several layers will be shown. the dentate gyrus has three layers of cells (or four if the hilus is included). the layers are from the outer in – the molecular layer, the inner molecular layer, the granular layer, and the hilus. the ca3 in the hippocampus proper has the following cell layers known as strata: lacunosum-moleculare, radiatum, lucidum, pyramidal, and oriens. ca2 and ca1 also have these layers except the lucidum stratum. the input to the hippocampus (from varying cortical and subcortical structures) comes from the entorhinal cortex via the perforant path. the entorhinal cortex (ec) is strongly and reciprocally connected with many cortical and subcortical structures as well as with the brainstem. different thalamic nuclei, (from the anterior and midline groups), the medial septal nucleus, the supramammillary nucleus of the hypothalamus, and the raphe nuclei and locus coeruleus of the brainstem all send axons to the ec, so that it serves as the interface between the neocortex and the other connections, and the hippocampus. the ec is located in the parahippocampal gyrus, a cortical region adjacent to the hippocampus. this gyrus conceals the hippocampus. the parahippocampal gyrus is adjacent to the perirhinal cortex, which plays an important role in the visual recognition of complex objects. there is also substantial evidence that it makes a contribution to memory, which can be distinguished from the contribution of the hippocampus. it is apparent that complete amnesia occurs only when both the hippocampus and the parahippocampus are damaged. circuitry image 4: basic circuit of the hippocampus, as drawn by cajal dg: dentate gyrus. sub: subiculum. ec: entorhinal cortex the major input to the hippocampus is through the entorhinal cortex (ec), whereas its major output is via ca1 to the subiculum. information reaches ca1 via two main pathways, direct and indirect. axons from the ec that originate in layer iii are the origin of the direct perforant pathway and form synapses on the very distal apical dendrites of ca1 neurons. conversely, axons originating from layer ii are the origin of the indirect pathway, and information reaches ca1 via the trisynaptic circuit. in the initial part of this pathway, the axons project through the perforant pathway to the granule cells of the dentate gyrus (first synapse). from then, the information follows via the mossy fibres to ca3 (second synapse). from there, ca3 axons called schaffer collaterals leave the deep part of the cell body and loop up to the apical dendrites and then extend to ca1 (third synapse). axons from ca1 then project back to the entorhinal cortex, completing the circuit. basket cells in ca3 receive excitatory input from the pyramidal cells and then give an inhibitory feedback to the pyramidal cells. this recurrent inhibition is a simple feedback circuit that can dampen excitatory responses in the hippocampus. the pyramidal cells gives a recurrent excitation which is an important mechanism found in some memory processing microcircuits. several other connections play important roles in hippocampal function. beyond the output to the ec, additional output pathways go to other cortical areas including the prefrontal cortex. a major output goes via the fornix to the lateral septal area and to the mammillary body of the hypothalamus (which the fornix interconnects with the hippocampus). the hippocampus receives modulatory input from the serotonin, norepinephrine, and dopamine systems, and from the nucleus reuniens of the thalamus to field ca1. a very important projection comes from the medial septal nucleus, which sends cholinergic, and gamma amino butyric acid (gaba) stimulating fibers (gabaergic fibers) to all parts of the hippocampus. the inputs from the medial septal nucleus play a key role in controlling the physiological state of the hippocampus; destruction of this nucleus abolishes the hippocampal theta rhythm and severely impairs certain types of memory. regions image 5: hippocampal location and regions areas of the hippocampus are shown to be functionally and anatomically distinct. the dorsal hippocampus (dh), ventral hippocampus (vh) and intermediate hippocampus serve different functions, project with differing pathways, and have varying degrees of place cells. the dorsal hippocampus serves for spatial memory, verbal memory, and learning of conceptual information. using the radial arm maze, lesions in the dh were shown to cause spatial memory impairment while vh lesions did not. its projecting pathways include the medial septal nucleus and supramammillary nucleus. the dorsal hippocampus also has more place cells than both the ventral and intermediate hippocampal regions. the intermediate hippocampus has overlapping characteristics with both the ventral and dorsal hippocampus. using anterograde tracing methods, cenquizca and swanson (2007) located the moderate projections to two primary olfactory cortical areas and prelimbic areas of the medial prefrontal cortex. this region has the smallest number of place cells. the ventral hippocampus functions in fear conditioning and affective processes. anagnostaras et al. (2002) showed that alterations to the ventral hippocampus reduced the amount of information sent to the amygdala by