primate basal ganglia primate basal ganglia the basal ganglia form a major brain system in all species of vertebrates, but in primates (including humans) there are special features that justify a separate consideration. as in other vertebrates, the primate basal ganglia can be divided into striatal, pallidal, nigral, and subthalamic components. in primates, however, there are two pallidal subdivisions called the external globus pallidus (gpe) and internal globus pallidus (gpi). also in primates, the dorsal striatum is divided by a large tract called the internal capsule into two masses named the caudate nucleus and the putamen—in most other species no such division exists, and only the striatum as a whole is recognized. beyond this, there is a complex circuitry of connections between the striatum and cortex that is specific to primates. this complexity reflects the difference in functioning of different cortical areas in the primate brain. diagram of the main components of the basal ganglia and their interconnections. gpe = globus pallidus external gpi = globus pallidus internal stn = subthalamic nucleus snpr = substantia nigra pars reticulata snpc = substantia nigra pars compacta glutamatergic pathways are red, dopaminergic pathways are magenta and gabaergic pathways are blue. functional imaging studies have been performed mainly using human subjects. also, several major degenerative diseases of the basal ganglia, including parkinson's disease and huntington's disease, are specific to humans, although "models" of them have been proposed for other species. corticostriatal connection a major output from the cortex, with axons from most of the cortical regions connecting to the striatum, is called the corticostriatal connection, part of the cortico-basal ganglia-thalamo-cortical loop. in the primate most of these axons are thin and unbranched. the striatum does not receive axons from the primary olfactory, visual or auditory cortices. the corticostriatal connection is an excitatory glutamatergic pathway. one small cortical site can project many axon branches to several parts of the striatum. striatum main article: striatum the striatum is the largest structure of the basal ganglia. neuronal constitution medium spiny neurons (msn)s, account for up to 95 per cent of the striatal neurons. there are two populations of these projection neurons, msn1 and msn2, both of which are inhibitory gabaergic. there are also various groups of gabaergic interneurons and a single group of cholinergic interneurons. these few types are responsible for the reception, processing, and relaying of all the cortical input. most of the dendritic spines on the medium spiny neurons synapse with cortical afferents and their axons project numerous collaterals to other neurons. the cholinergic interneurons of the primate, are very different from those of non-primates. these are said to be tonically active. the dorsal striatum and the ventral striatum have different populations of the cholinergic interneurons showing a marked difference in shape. physiology unless stimulated by cortical input the striatal neurons are usually inactive. levels of organisation the striatum is one mass of grey matter that has two different parts, a ventral and a dorsal part. the dorsal striatum contains the caudate nucleus and the putamen, and the ventral striatum contains the nucleus accumbens and the olfactory tubercle. the internal capsule is seen as dividing the two parts of the dorsal striatum. sensorimotor input is mostly to the putamen. an associative input goes to the caudate nucleus and possibly to the nucleus accumbens. there are two different components of the striatum differentiated by staining – striosomes and a matrix. striosomes are located in the matrix of the striatum and these contain μ-opioid receptors and dopamine receptor d1 binding sites. the striatopallidal fibers give a connection from the putamen to the globus pallidus and substantia nigra. connectomics unlike the inhibitory gabaergic neurons in the neocortex that only send local connections, in the striatum these neurons send long axons to targets in the pallidum and substantia nigra. a study in macaques showed that the medium spiny neurons have several targets. most striatal axons first target the gpe, some of these also target the gpi and both parts of the substantia nigra. there are no single axon projections to either the gpi, or to the sn, or to both of these areas; only connecting as continuing targets via axon collaterals from the striatum to the gpe. the only difference between the axonal connectomes of the striosomes and the axons of those neurons in the matrix, is in the numbers of their branching axons. striosomal axons cross the extent of the sn, and in macaques emit 4 to 6 vertical collaterals that form vertical columns which enter deep into the sn pars compacta (snpc); the axons from those in the matrix are more sparsely branched. this pattern of connectivity is problematic. the main mediator of the striatopallidonigral system is gaba and there are also cotransmitters. the gpe stains for met-enkephalin, the gpi stains for either substance p or dynorphin or both, and the sn stains for both. this probably means that a single axon is able to concentrate different co-mediators in different subtrees, depending on the target. selectivity of striatal territories for targets a study of the percentage of striatal axons from the sensorimotor (dorsolateral putamen) and associative striatum (caudate nucleus and ventromedial putamen) to the globus pallidus found important differences. the gpe for instance receives a large input of axons from the associative areas. the gpi is strongly sensorimotor connected. the sn is at first associative. this is confirmed by the effects of striatal stimulations. all the projections from the primary somatosensory cortex to the putamen, avoid the striosomes and innervate areas within the matrix. pallidonigral set and pacemaker constitution the pallidonigral set comprises the direct targets of the striatal axons: the two nuclei of the pallidum, and the pars compacta (snpc) and pars reticulata (snpr) of the substantia nigra. one character of this ensemble is given by the very dense striato-pallidonigral bundle giving it its whitish aspect (pallidus means pale). after foix and nicolesco (1925) and some others, cécile and oskar vogt (1941) suggested the term pallidum - also used by the terminologia anatomica (1998). they also proposed the term nigrum for replacing nigra, which is indeed not a substance; but this is generally not followed. the whole pallidonigral set is made up the same neuronal components. the majority is made up of very large neurons, poorly branched, strongly stained for parvalbumin, having very large dendritic arborisations (much larger in primates than in rodents) with straight and thick dendrites. only the shape and direction of the dendritic arborizations differ between the pallidum and the sn neurons. the pallidal dendritic arborisations are very large flat and disc-shaped. their principal plane is parallel to the others and also parallel to the lateral border of the pallidum; thus perpendicular to the axis of the afferences. since the pallidal discs are thin, they are crossed only for a short distance by striatal axons. however, since they are wide, they are crossed by many striatal axons from wide striatal parts. since they are loose, the chances of contact are not very high. striatal arborisations emit perpendicular branches participating in flat bands parallel to the lateral border, which increases the density of synapses in this direction. this is true for not only for the striatal afferent but also for the subthalamic (see below). the synaptology of the set is uncommon and characteristic. the dendrites of the pallidal or nigral axons are entirely covered by synapses, without any apposition of glia. more than 90% of synapses are of striatal origin. one noticeable property of this ensemble is that not one of its elements receives cortical afferents. initial collaterals are present. however, in addition to the presence of various appendages at the distal extremity of the pallidal neurons that could act as elements of local circuitry, there are weak or no functional interrelations between pallidal neurons. external globus pallidus the external globus pallidus (gpe) or lateral globus pallidus, is flat, curved and extended in depth and width. the branching dendritic trees are disc-shaped, flat, run parallel to each other and to the pallidum border, and are perpendicular to those axons coming from the striatum. the gpe also receives input from the subthalamic nucleus, and dopaminergic input from the snpc. the gpe does not give output to the thalamus only intrasystemically connecting to the other basal ganglia structures. it can be seen as a gaba inhibitory mediator regulating the basal ganglia. its firing activity is very fast and exhibits long intervals of up to several seconds of silence. in monkeys an initial inhibition was seen in response to striatal input, followed by a regulated excitation. in the study this suggested that the excitation was used temporarily to control the magnitude of the incoming signal and to spatially focus this into a limited number of pallidal neurons. gpe neurons are often multi-targeted and may respond to a number of neuron types. in macaques, axons from the gpe to the striatum account for about 15%; those to the gpi, snpr and subthalamic nucleus are about 84%. the subthalamic nucleus was seen to be the preferred target which also sends most of its axons to the gpe. internal globus pallidus the internal globus pallidus (gpi) or medial globus pallidus is only found in the primate brain and so is a younger portion of the globus pallidus. like the gpe and the substantia nigra the gpi is a fast-spiking pacemaker but its activity does not show the long intervals of silence seen in the others. in addition to the striatal input there is also dopaminergic input from the snpc. unlike the gpe the gpi does have a thalamic output and a smaller output towards the habenula. it also gives output to other areas including the pedunculopontine nucleus and to the area behind the red nucleus. the evolutionary increase of the internal pallidus also brought an associated increase in the pallidothalamic tracts, and the appearance of the ventral lateral nucleus in the thalamus. the mediator is gaba. substantia nigra main article: substantia nigra micrograph of neurons containing neuromelanin (arrows) in the substantia nigra of a rhesus monkey. nissl stain (blue). scale bar = 30 microns (0.03 millimeters). the substantia nigra is made up of two parts, the pars compacta (snpc) and the pars reticulata (snpr), sometimes there is a reference to the pars lateralis but that is usually included as part of the pars reticulata. the ‘’black substance’’ that the term translates as, refers to the neuromelanin found in the dopaminergic neurons. these are found in a darker region of the snpc. the snpr is a lighter coloured region. there are similar cells in the substantia nigra and the globus pallidus. both parts receive input from the striatopallidal fibres. pars compacta the pars compacta is the most lateral part of the substantia nigra and sends axons to the superior colliculus. the neurons have high firing rates which make them a fast-spiking pacemaker and they are involved in ocular saccades. pars reticulata the border between the snpc and snpr is highly convoluted with deep fringes. its neuronal genus is the same as that of the pallidum, with the same thick and long dendritic trees. it receives its synapses from the striatum in the same way as the pallidum. striatonigral axons from the striosomes may form columns vertically oriented entering deeply in the snpr. the ventral dendrites of the snpc from the reverse direction go also deeply in it. the sn also send axons to the pedunculopontine nucleus. and to the parafascicular part of the central complex. the snpr is another "fast-spiking pacemaker" stimulations provoke no movements. confirming anatomical data, few neurons respond to passive and active movements (there is no sensorimotor map) "but a large proportion shows responses that may be related to memory, attention or movement preparation" that would correspond to a more elaborate level than that of the medial pallidum. in addition to the massive striatopallidal connection, the snpr receives a dopamine innervation from the snpc and glutamatergic axons from the pars parafascicularis of the central complex. it sends nigro-thalamic axons. there is no conspicuous nigro-thalamic bundle. axons arrive medially to the pallidal afferences at the anterior and most medial part of the lateral region of the thalamus: the ventral anterior nucleus (va) differentiated from the ventral lateral nucleus (vl) receiving pallidal afferences. the mediator is gaba. striatopallidonigral connection the striatopallidonigral connection is a very particular one. it