Interneurons of the motor region of the neocortex]

Interneurons of motor area in the brain cortex have been studied in cats and monkeys. The greatest attention has been paid to pyramidal interneurons, among which six cell types have been described according to their axonal composition. Unlike stellate interneurons, all types of pyramidal interneurons possess less developed axonal collaterals. Interneuronal contacts are situated on dendrites or cell bodies of middle and large long-axonal pyramids. Functional role of cortical interneurons seems to be different. Some of them are of inhibitory nature (basket cells and, perhaps, other types of long-axonal stellate neurons), others are exciting elements. The latter include short-axonal stellate neurons and, perhaps, pyramidal interneurons. While comparing the cortex in cats and monkeys, it is evident that the neocortex in monkeys, especially its lower layers, is rich in pyramidal interneurons.     

Projection of the neurons of the substantia nigra and ventral field of the midbrain tegmen in the cat to the putamen

By means of retrograde axonal transport of the horseradish peroxidase and fluorochromes in the cat, it has been stated that neurons of all the parts of the substantia nigra (SN) make projections to the putamen. These projections are organized in such a way that the rostral part of the putamen gets the projected fibers from less number of the SN parts than the caudal part. To the caudal part of this formation all parts of the SN are projected, and in the equal degree to its dorsal and ventral segments. Projections to the rostral part are sent only from two parts of the SN--compact and dorsal. To the dorsal segment of this part only axons from a small amount of the nigral neurons are sent. A small amount of neurons of the tegmental ventral field give projections to the ventral segments along the whole rostrocaudal extent of the putamen. Convergence of the SN neuronal axons in the formations of the striated body has been determined, as well as overlapping of the terminal fields in the putamen from the projective neurons of the nigral various parts. Besides in different parts of the SN discrepancy has been revealed in the neuronal populations, labelled with different stainings, that contain cells, marked with two markers, injected into the nucleus caudatus and into the putamen.     

Neurons forming striatonigral connections in the rat brain

Using the retrograde axonic transport of horseradish peroxidase method the striatal neurons projections to substance nigra have been studied in rats. After peroxidase injection into substance nigra a considerable number of small and medium sized neurons (10-20 mkm) become labelled in the ipsilateral striatum. Large labelled striatal cells (20-25 mkm) have been found. Among labelled striatal neurons multipolar cells with triangular and oval body prevailed. The number of cells with elongated multipolar or spindle-shaped body was less. The data obtained disprove the conception that only large ("giant") neurons form the efferent striatal pathways to substance nigra.     

Neuronal activity of the monkey striatum points at the integration of successive actions into functional blocks

In order to study the role of the striatum in generation of multistage behavior, the spike activity of 148 cells was recorded in the monkey brain putamen. Two kinds of neuron responses were observed. Phasic response involved activity during only one stage of the behavior program, and tonic response involved activity during more than one sequential stage. The tonic responses were recorded in 132 neurons out of 148, 11 neurons responding only as tonic. Other 121 cells show under different conditions both tonic and phasic responses. Beginnings and ends of "tonic" responses as a rule corresponded to the start and completion of the nearest behavioral aim. The obtained data suggest that the neuron activity of striatum is related not only to the control of individual movements but also to the whole structure of behavior.     

Localization and morphometric analysis of masticatory muscle afferent neurons in the nucleus of the mesencephalic root of the trigeminal nerve in the cat

Injections of horseradish peroxidase (HRP) were made into the ipsilateral temporal muscle and contralateral masseter muscle of 10 cats in order to identify and characterize neurons in the nucleus of the mesencephalic root of the trigeminal nerve that innervate muscle receptors in the orofacial periphery. Neurons labelled by HRP injections and unlabelled cells from 5 control cats were measured with a computer-based image analyzer, and their position was mapped on a stereotaxic graph. Cells that innervate the masseter and temporal muscles were identified throughout the rostrocaudal extent of the nucleus. There was no indication of a somatotopic pattern nor of a specific segregation within the nucleus for cells innervating muscle receptors. The nucleus contained small, rounded unipolar neurons located primarily in the dorsal border of the periaqueductal gray (PAG) matter in the rostral part of the nucleus and larger oval unipolar neurons which were scattered throughout the nucleus, but were predominant in the pontine portion of the nucleus. HRP injections labelled both large and small cells, as well as occasional multipolar cells. The last-mentioned tended to be located in the lateral margins of the PAG. The mean geometric values obtained for the control group were: area 552.7 microns2 perimeter 110.3 microns; maximum diameter 36.0 microns. and diameter of an equivalent circle 26.1 microns. The mean values of the labelled neurons were: area 606.6 microns2; perimeter 100.1 microns; maximum diameter 36.0 microns, and diameter of an equivalent circle 27.2 microns.     

Separate populations of neurons in the oculomotor nucleus project to the cerebellum and the abducent nucleus. A retrograde fluorescent double-labelling study in the cat

Retrograde transport of fluorescent substances was used in order to investigate possible branching of axons from neurons in the oculomotor nucleus in the cat. Rhodamine-B-isothiocyanate (RITC) was injected into the cerebellar hemisphere, while Fluoro-Gold was implanted into the abducent nucleus. Neurons single-labelled with either of the dyes were found in the oculomotor nucleus in all cases, but no double-labelled neurons were found. The labelled cells were smaller than motoneurons and located in partly overlapping areas along the dorsal border of the oculomotor nucleus, with the RITC labelled cerebellar projecting cells concentrated medially and the Fluoro-Gold labelled neurons projecting to the abducent nucleus concentrated laterally. The RITC labelled cells were found throughout the rostrocaudal extent of the nucleus, while the Fluoro-Gold labelled cells were mainly found caudally. The present findings demonstrate that oculomotor neurons projecting to the feline cerebellum and abducent nucleus represent separate cell populations.     

Cholinergic interneurons are differentially distributed in the human striatum

Background

The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response.

Methodology/Principle Findings

This study was carried out using stereological methods to examine the volume and density (cells/mm³) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum.

Conclusions/Significance

All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a special integration of information by interneurons. Interestingly, these striatal regions have been very much left out in functional studies.     

A New Subdivision,Marginal Division,in the Neostriatum of the Monkey Brain

A new subdivision, the marginal division (MrD), was discovered at the caudal border of the striatum and surrounds the rostral edge of the globus pallidus in the rat brain in our previous studies. The neuronal somata of the MrD are mostly fusiform in shape with their long axes lining dorsoventrally. The MrD is more densely filled with substance P (SP)-, Leucine-enkephalin (L-Enk)-, dynorphin B-, neurotensin-, somatostatin- and cholecystokinin (CCK)-immunoreactive fibers and terminal-like structures than the rest of the striatum. The MrD was confirmed in the cat neostriatum as well. The present study intended to explore whether the MrD exists in the monkey neostriatum (putamen) with Nissl, histochemical and immunohistochemical methods. A band of fusiform neurons were obviously identified at the caudomedial edge of the putamen. These neurons lie outside the lateral medullary lamina and indirectly surround the rostrolateral border of the globus pallidus. The abundance of SP-, L-Enk-, neuropeptide Y-, CCK-, dopamine- and serotonin-positive fibers and terminal-like structures with a few positive fusiform neurons accumulating at the caudomedial border of the putamen obviously distinguishes this zone from the rest of neostriatum and globus pallidus. The acetylcholinesterase (AChE) positive and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) containing fusiform neurons are distinctly visualized in the same zone. The morphological figure and the location of these neurons, and the histochemical and immunohistochemical characteristics of this area coincide well with those of the MrD in the rat and cat striatum. This study thus convincingly identifies the existence of the MrD in the monkey neostriatum. It is fairly asserted that the MrD is a universal structure in the mammalian brain.     

Ultrastructural Morphology of Neuronal Death Following Reversible Focal Ischemia in the Rat

Electron microscopy and terminal deoxynucleotidyl transferase (TdT) mediated dUTP-biotin nick end-labelling (TUNEL) were used to illustrate the different stages and subcellular alterations of cell degeneration that occur in the striatum of the rat after transient focal ischemia. Degenerating neurons exhibited different morphological types: apoptosis Type 1 (aggregation of dense masses of chromatin beneath the 'intact' nuclear membrane) and Type 2 (high cytoplasmic vacuolization), and necrosis. These profiles were localized in different part of the striatum. Type 1 was found in the head of the caudate putamen, Type 2 in the middle part of the striatum and necrosis in the striatal core. These ultrastructural results demonstrated that apoptosis occurs in neurons following focal ischemia in the striatal penumbra. In contrast, necrosis can be observed in the ischemic core, the region maximally affected by the ischemia. Finally, the presence of astrocytes throughout both the penumbra and ischemic core displaying numerous cytoplasmic vacuoles suggested an activation of glial cells.     

Cholinergic interneuron characteristics and nicotinic properties in the striatum

The neostriatum (dorsal striatum) is composed of the caudate and putamen. The ventral striatum is the ventral conjunction of the caudate and putamen that merges into and includes the nucleus accumbens and striatal portions of the olfactory tubercle. About 2% of the striatal neurons are cholinergic. Most cholinergic neurons in the central nervous system make diffuse projections that sparsely innervate relatively broad areas. In the striatum, however, the cholinergic neurons are interneurons that provide very dense local innervation. The cholinergic interneurons provide an ongoing acetylcholine (ACh) signal by firing action potentials tonically at about 5 Hz. A high concentration of acetylcholinesterase in the striatum rapidly terminates the ACh signal, and thereby minimizes desensitization of nicotinic acetylcholine receptors. Among the many muscarinic and nicotinic striatal mechanisms, the ongoing nicotinic activity potently enhances dopamine release. This process is among those in the striatum that link the two extensive and dense local arbors of the cholinergic interneurons and dopaminergic afferent fibers. During a conditioned motor task, cholinergic interneurons respond with a pause in their tonic firing. It is reasonable to hypothesize that this pause in the cholinergic activity alters action potential dependent dopamine release. The correlated response of these two broad and dense neurotransmitter systems helps to coordinate the output of the striatum, and is likely to be an important process in sensorimotor planning and learning.     

The distribution of cholinergic neurons in the human central nervous system

Choline acetyltransferase (ChAT), the enzyme responsible for the biosynthesis of acetylcholine, is presently the most specific marker for identifying cholinergic neurons in the central and peripheral nervous systems. The present article reviews immunohistochemical and in situ hybridization studies on the distribution of neurons expressing ChAT in the human central nervous system. Neurons with both immunoreactivity and in situ hybridization signals of ChAT are observed in the basal forebrain (diagonal band of Broca and nucleus basalis of Meynert), striatum (caudate nucleus, putamen and nucleus accumbens), cerebral cortex, mesopontine tegmental nuclei (pedunculopontine tegmental nucleus, laterodorsal tegmental nucleus and parabigeminal nucleus), cranial motor nuclei and spinal motor neurons. The cerebral cortex displays regional and laminal differences in the distribution of neurons with ChAT. The medial septal nucleus and medial habenular nucleus contain immunoreactive neurons for ChAT, which are devoid of ChAT mRNA signals. This is probably because there is a small number of cholinergic neurons with a low level of ChAT gene expression in these nuclei of human. Possible connections and speculated functions of these neurons are briefly summarized.     

Cytology of large neurons in the guinea pig dorsal cochlear nucleus contacting the inferior colliculus

Large neurons in the dorsal cochlear nucleus of the guinea pig which project to the inferior colliculus were identified after injections of the neural tracer WGA-HRP. Retrograde labelled cells (pyramidal and giant neurons) in the dorsal cochlear nucleus were glycine and GABA immunonegative and showed a similar ultrastructure. Between 30 and 60% of their perimeter was covered by axo-somatic boutons, most of which (>50%) contained pleomorphic synaptic vesicles. Other boutons (about 40% of total) contained flat vesicles and few (5-6%) contained round vesicles, a characteristic of the excitatory cells innervating the inferior colliculus. Immunogold-cytochemistry, coupled to silver intensification, showed that more than 50% of axo-somatic pleomorphic boutons and over 90% of boutons containing flat and pleomorphic vesicles store glycine. Rare WGA-HRP labelled axo-somatic boutons containing flat-pleomorphic vesicles were seen on pyramidal and giant neurons. This suggests that a few inhibitory collicular terminals contact the excitatory large neurons in the dorsal cochlear nucleus.     

Two populations of somatostatin-immunoreactive neurons in the guinea pig striatum

Summary Two populations of neurons displaying somatostatin-like immunoreactivity were detected immunohistochemically in the guinea pig striatum using a monoclonal antibody. Sparse, well-stained neurons similar to those described in other species were observed throughout the guinea pig caudate-putamen. These neurons contained both neuropeptide Y and NADPH-diaphorase in addition to somatostatin. A second large population of somatostatin immunoreactive neurons in which these other substances did not coexist was found within the putamen.     

Populations of behavior-reactive neurons in the monkey neostriatum

Comparative analysis of the unit activity of the monkey putamen during multistage behavior showed that neurons of the putamen are active during all the behavioral actions. It was established that the number of the behavior-related neurons changes considerably less than number of neurons which reorganize their activity at the time. Reorganization of unit activity in the putamen is considered as reflecting the efferent code which controls behavior, and the degree of reorganization--as a measure of change of this code in relation to organization of ongoing behavioral action. It has been discovered that the change in the number of the active neurons at various steps of behavior and reorganization of their activity occurs independently. It may be related to two main afferent systems of striatum: ascending from rhe brain stem, and corticofugal which brings differentiated information to the neuronal net of striatum from various parts of the cortex.     

Neurons of the human basal ganglia (striatum and basolateral amygdala) expressing the enzyme NADPH-d

In human striatum and basolateral amygdala NADPH-d+ neurons were revealed (after Vincent et al., 1983); and in striatum strio-cortical neurons were also revealed using DiI marker (after Dahtstrom and Belichenko, 1995). The NADPH-d+ neurons were numerous in both formations. Staining of NADPH-d+ neurons with their processes, and our previous study of striatal and amygdalar human neurons by Golgi method made it possible to identify the species of neurons with their assessment as sparsely or densely branched. The main efferent neurons of striatum and basolateral amygdala (densely branched medium spiny and bushy spiny, respectively) and their densely branched interneurons were not marked. Efferent NADPH-d+ neurons included the most numerous ones in both formations. A projection of reticular striatal neurons to cortex was also shown. The NADPH-d+ interneurons belonged to sparsely branched forms. In striatum they included slender-dendritic and long-dendritic bipolars (numerous), ordinary bipolars, twisted and large poor-dendritic cells; in amygdala--the same bipolars and radial cells. Thus, the NADPH-d positive cells in the formations under study were represented by more "ancient" or less structurally complex cell forms.     

In Vivo Electrochemical Studies of Dopamine Overflow and Clearance in the Striatum of Normal and MPTP-Treated Rhesus Monkeys

Abstract: Rapid chronoamperometric recordings, using Nafion-coated carbon-fiber electrodes (30–90 µm o.d.), were used to investigate overflow and uptake of dopamine (DA) in the striatum of normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys. The monkeys were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging-guided sterile stereotaxic procedures were used for implantations of the electrochemical electrodes coupled with single-barrel micropipettes that were used to apply potassium or DA locally. Potassium evoked a robust overflow of DA-like electrochemical signals into the brain extracellular space in the unlesioned or normal putamen and caudate nucleus of the rhesus monkeys. In contrast, potassium did not produce any detectable changes (> 97% depletion) of DA in the MPTP-lesioned striatum. In addition, the diffusion/clearance of locally applied DA was markedly altered in the lesioned caudate nucleus and putamen compared with unlesioned striatum. Cell counts of the number of residual tyrosine hydroxylase-positive neurons in MPTP-treated monkeys, in conjunction with whole-tissue levels of DA and its metabolites, showed that the MPTP lesions produced extensive damage of the nigrostriatal DA system. These data indicate that residual dopaminergic fibers remaining after MPTP lesions are dysfunctional and have a greatly diminished capacity for high-affinity DA uptake.     

Sources of thalamic afferents projecting to the suprasylvian gyrus of the black sea porpoise

Neurons sending fibers to different loci of the suprasylvian gyrus (SSG) of the porpoise(Phocaena phocaena) cortex were located in the thalamus by retrograde horseradish peroxidase transport and fluorescent tracing techniques. Horseradish peroxidase injection into the anterior section of the suprasylvian gyrus led to retrograde labelling of neurons in the lateral portion of the ventrobasal complex of nuclei and the ventroposteroinferior nucleus. A group of labelled cells was found in the ventral section of the main medial geniculate nucleus. Injecting bisbenzimide into different loci of the medial suprasylvian gyrus also led to retrograde labelling of neurons belonging to the ventral division of the main medial geniculate nucleus. Somewhat lower numbers of labelled cells were found in the inferior nucleus of the pulvinar. Small groups of labelled neurons were also found in the lateral nucleus of the pulvinar, the medioventral nucleus of the medial geniculate body, and the posterior complex of nuclei. A similar distribution of labelled cells was also observed after injecting bisbenzimide into the more caudal portion of the gyrus, although the location of labelled cells in the ventral division of the main medial geniculate nucleus and the lower pulvinar nucleus were shifted in a lateral direction.A. N. Severtsov Institute of Animal Evolutionary Moprhology and Ecology, Academy of Sciences of the USSR, Moscow. National University, Singapore. Translated from Neirofiziologiya, Vol. 21, No. 4, pp. 529–539, July–August, 1989.     

Striatal Expression of Glutamic Acid Decarboxylase Gene in Alzheimer's Disease

Abstract: To examine potential alteration of GABAergic striatal neurons in Alzheimer's disease, we used quantitative in situ hybridization to analyze the messenger RNA coding for M_r 67,000 glutamic acid decarboxylase (GAD₆₇ mRNA) in the striatum of five patients with Alzheimer's disease (AD) and nine matched control subjects. We found a 51–57% increase in the optical density of hybridization signal in the caudate nucleus and putamen, corresponding to a 30–42% increase in the number of neurons expressing a detectable amount of GAD₆₇ mRNA. By contrast, no alteration was observed in the ventral striatum. The expression of GAD₆₇ mRNA per neuron was similar in AD and control subjects both in the dorsal and ventral striatum. Taken together, our data indicate that, in AD, GABAergic neurotransmission is increased in the dorsal striatum but not in the ventral striatum. We suggest that this increased GABAergic neurotransmission may explain extrapyramidal signs often observed in AD.     

Role of the basal ganglia in the occurrence of paradoxical sleep dreams (hypothetical mechanism)

A hypothetical mechanism of the basal ganglia involvement in the occurrence of paradoxical sleep dreams and rapid eye movements is proposed. According to this mechanism, paradoxical sleep is provided by facilitation of activation of cholinergic neurons in the pedunculopontine nucleus as a result of suppression of their inhibition from the output basal ganglia nuclei. This disinhibition is promoted by activation of dopaminergic cells by pedunculopontine neurons, subsequent rise in dopamine concentration in the input basal ganglia structure. striatum, and modulation of the efficacy of cortico-striatal inputs. In the absence of signals from retina, a disinhibition of neurons in the pedunculopontine nucleus and superior colliculus allows them to excite neurons in the lateral geniculate body and other thalamic nuclei projecting to the primary and higher visual cortical areas, prefrontal cortex and back into the striatum. Dreams as visual images and "motor hallucinations" are the result of an increase in activity of definitely selected groups of thalamic and neocortical neurons. This selection is caused by modifiable action of dopamine on long-term changes in the efficacy of synaptic transmission during circulation of signals in closed interconnected loops, each of which includes one of the visual cortical areas (motor cortex), one of the thalamic nuclei, limbic and one of the visual areas (motor area) of the basal ganglia. pedunculopontine nucleus, and superior colliculus. Simultaneous modification and modulation of synapses in diverse units of neuronal loops is provided by PGO waves. Disinhibition of superioir colliculus neurons and their excitation by pedunculopontine nucleus lead to an appearance of rapid eye movements during paradoxical sleep.