Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics

Using a new and unbiased stereological technique, the total numbers of neuron and glial cells in the mediodorsal thalamic nucleus and the nucleus accumbens were found to be significantly reduced in schizophrenic patients compared with controls. The total neuron and glial cell number in the ventral pallidum and in the basolateral nucleus of amygdala did not differ in the two groups.     

Stereological quantitation of human brains from normal and schizophrenic individuals

The complex organization and high density of nerve cells in the human brain presents a challenge to the estimation of total cell numbers. The first unbiased counting method, the disector, was described in 1984 and has since made it possible to accurately count total neuron numbers in any region that can be defined, while excluding artifacts of earlier counting methods. The disector method has been applied to normal neocortex and to four subcortical brain regions from schizophrenics and controls. The total neuron number in neocortex in 26 normal individuals was estimated to be 25·10⁹. A 40 and 50% reduction of total nerve cell number was found in the mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics, respectively. Furthermore, the Cavalieri principle has been used to estimate the volume of human cortex, white matter, central grey regions and the volume of the ventricular system in both controls and schizophrenics. As shown by these studies, the introduction of unbiased stereological methods and subsequent modifications in recent years have made it possible to estimate a number of parameters in the human brain without the biases included in most classical works. By comparison, earlier conventional counting methods have been relatively time consuming, mostly biased to a smaller or larger degree, and generally less precise. The application of these new neurostereological methods will undoubtedly provide greater confidence for future brain studies.     

Thalamic afferents to prefrontal cortices from ventral motor nuclei in decision‐making

The focus of this literature review is on the three interacting brain areas that participate in decision‐making: basal ganglia, ventral motor thalamic nuclei, and medial prefrontal cortex, with an emphasis on the participation of the ventromedial and ventral anterior motor thalamic nuclei in prefrontal cortical function. Apart from a defining input from the mediodorsal thalamus, the prefrontal cortex receives inputs from ventral motor thalamic nuclei that combine to mediate typical prefrontal functions such as associative learning, action selection, and decision‐making. Motor, somatosensory and medial prefrontal cortices are mainly contacted in layer 1 by the ventral motor thalamic nuclei and in layer 3 by thalamocortical input from mediodorsal thalamus. We will review anatomical, electrophysiological, and behavioral evidence for the proposed participation of ventral motor thalamic nuclei and medial prefrontal cortex in rat and mouse motor decision‐making.     

Collateral innervation of the medial and lateral prefrontal cortex by amygdaloid, thalamic, and brain-stem neurons

The distribution of the afferents to the rat's prefrontal cortex originating in the thalamic mediodorsal nucleus and the amygdala was investigated with two fluorescent tracers. Special emphasis was laid on detecting the loci of neurons which project via axonal collaterals into both lateral and medial portions of the prefrontal cortex. It was found that a high number of neurons of the anterior portion of the basolateral amygdaloid nucleus terminate via collaterals in both the medial and lateral subfields of the prefrontal cortex. On the other hand, only a small number of mediodorsal thalamic cells were found to project to both sides of the prefrontal hemisphere via bifurcating axonal collaterals. These cells were situated exclusively in the lateral part of the medial segment of the mediodorsal nucleus. The majority of both thalamic and amygdaloid neurons with bifurcating axons originate from subregions whose cells innervate primarily the medial prefrontal cortex. In brain-stem, neurons of the nucleus raphé dorsalis also project via collaterals to the medial and lateral prefrontal regions. Furthermore, neurons of the dorsal and ventral premamillary nuclei, the lateral mamillary nucleus, the ventral tegmental area of Tsai, and the ventral tegmental nucleus of Gudden were found to project to the medial prefrontal cortex. Our results indicate a differential collateral organization of thalamic and amygdaloid afferents to prefrontal cortical fields. The anterior basolateral amygdala (which innervates via collaterals both the medial and lateral prefrontal subfields) may add a common input to either subfield, such as information on the significance of incoming stimuli to the animal's behavior, while the mediodorsal nucleus (whose segments are principally connected to only one prefrontal subfield) may add segment-specific information, for example, of a spatial-cognitive nature for the lateral segment and of an emotional nature for the central and medial segments. The existence of a basolateral limbic circuit, composed of the amygdala, the thalamic mediodorsal nucleus, and the prefrontal cortex, is confirmed and knowledge on its interconnectivity is extended. From an anatomical point of view these data provide arguments for both unitary and diverging functions of the prefrontal cortex.     

Ventral striatopallidothalamic projection: IV. Relative involvements of neurochemically distinct subterritories in the ventral pallidum and adjacent parts of the rostroventral forebrain

Retrograde and anterograde tract-tracing studies were carried out to determine whether the capacity of the nucleus accumbens to influence the thalamic mediodorsal nucleus via ventral striatopallidothalamic connections disproportionately favors the shell over the core subterritory. After injections of Fluoro-Gold into the mediodorsal thalamic nucleus, retrogradely labeled neurons were detected in sections also processed for calbindin-D 28-kD and neurotensin immunoreactivities to facilitate identification of subterritories in the ventral pallidum. Fluoro-Gold-labeled cells were counted in series of sections cut through the ventral pallidum, rostral globus pallidus, nucleus of the vertical limb of the diagonal band, preoptic region, lateral hypothalamus, and the sublenticular gray region, including parts of the extended amygdala. Data were expressed as cells/unit area and as percentages of all labeled forebrain cells. Mediodorsal nucleus-projecting rostroventral forebrain neurons were most numerous in the ventromedial part of the subcommissural ventral pallidum and pallidal parts of the olfactory tubercle. Few were observed in the dorsolateral part of the subcommissural ventral pallidum. In addition, following injections into the ventral pallidum, anterogradely transported biotinylated dextran amine was evaluated in sections processed for calbindin or tyrosine hydroxylase immunoreactivities. Injection into the ventromedial part of the subcommissural ventral pallidum resulted in robust anterograde labeling of the medial segment of the mediodorsal nucleus and ventral tegmental area and weak labeling of the substantia nigra and subthalamic nucleus. Conversely, after injection into the dorsolateral part of the subcommissural ventral pallidum, anterograde labeling was weak in the mediodorsal nucleus and ventral tegmental area, but robust in the substantia nigra and subthalamic nucleus. The results are consistent with a predominant accumbens shell influence on the mediodorsal nucleus and with cortico-ventral striatopallidal-thalamocortical pathways that begin and end in different parts of the frontal lobe. © 1996 Wiley-Liss, Inc.     

Thalamic paraventricular nucleus neurons collateralize to innervate the prefrontal cortex and nucleus accumbens

The prefrontal cortex and nucleus accumbens are primary recipients of medial thalamic inputs, prominently including projections from the thalamic paraventricular nucleus. It is not known if paraventricular neurons collateralize to innervate both the prefrontal cortex and nucleus accumbens. We used dual retrograde tract tracing methods to examine this question. A small population of paraventricular neurons was found to innervate the prefrontal cortex and medial nucleus accumbens. These data suggest that the thalamic paraventricular nucleus may coordinately influence activity in the prefrontal cortex and ventral striatum.     

Dual olfactory representation in the rat thalamus: an anatomical and electrophysiological study

A combination of electrophysiological and anatomical techniques was used to determine the sites of termination of olfactory projections to the thalamus and the distribution of the cells of origin of these projections within the olfactory cortex. Following electrical stimulation of the olfactory bulb, short-latency unit responses were recorded not only in the central segment of the mediodorsal thalamic nucleus but also in the ventral and anterior parts of the submedial thalamic nucleus. Responses were not obtained in the ventral or lateral parts of the mediodorsal nucleus, in the dorsal part of the submedial nucleus, or in the intralaminar nuclei between the mediodorsal and submedial nuclei. The cells of origin of the projection were identified by making injections of horseradish peroxidase conjugated to wheat germ agglutinin (HRP WGA) into the thalamus and examining the olfactory cortex for retrogradely labeled cells. Following injections into the mediodorsal nucleus, labeled cells were found in the polymorphic cell zone deep to the olfactory tubercle, in the ventral endopiriform nucleus deep to the piriform cortex, and in an equivalent position deep to the periamygdaloid and lateral entorhinal cortices. After injections into the submedial nucleus, a smaller number of labeled cells were found in similar locations, except that they were restricted to the rostral olfactory cortical areas and were not found deep to the lateral part of the piriform cortex. Retrogradely labeled cells and anterogradely labeled axons were also found in the lateral orbital and ventral agranular insular areas of the prefrontal cortex with injections into the mediodorsal nucleus, and in the ventrolateral orbital area with injections into the submedial nucleus. Anterograde tracing experiments, using the autoradiographic method, have confirmed these results. Injections of 3H-leucine deep to the junction between the anterior piriform cortex and the olfactory tubercle label axons in both the central segment of the mediodorsal nucleus and the ventral part of the submedial nucleus, while injections deep to the posterior piriform cortex label axons in the mediodorsal nucleus only. Within the mediodorsal nucleus, the projection also appears to be organized so that fibers which arise more rostrally terminate ventrolaterally in the central segment, while fibers which arise more caudally terminate more dorsomedially. These results indicate that there is a substantial and possibly dual thalamocortical mechanism available for processing of olfactory stimuli.     

Converging projections from the mediodorsal thalamic nucleus and mesencephalic dopaminergic neurons to the neocortex in three species

Previous studies in the rat have shown that the neocortical dopaminergic afferents, originating in the mesencephalon, terminate in those areas of the frontal lobe which receive projections from the mediodorsal thalamic nucleus i.e., the prefrontal cortex. In order to clarify whether this overlap is accidental for the rat or a consistent feature of several species we have compared the projection areas of the ventral tegmental area and the mediodorsal thalamic nucleus in three species, rat, opossum and tree shrew, using HRP injections in combination with glyoxylic acid histofluorescence method. The results have shown, first, that the area innervated by the mediodorsal nucleus of the thalamus is localized in a different part of the frontal lobe in each species: dorsolateral in the opossum, anteromedial, polar and suprarhinal in the rat and frontopolar in the tree shrew. Secondly, this area alone in each species receives projections from the ventral tegmental area. Thirdly, this area alone receives a dense innervation in the deep cortical layers by fluorescent fibres probably containing dopamine. The neighbouring neocortical areas receive afferents neither from the mediodorsal nucleus of the thalamus nor from the ventral mesencephalic tegmentum; their catecholamine innervation is mainly confined to the superficial layers and appears to be of noradrenergic nature. Although the techniques used did not allow a precise determination of the borders of the two projection areas and, therefore, the exact degree of overlap, it appears that mesencephalic dopaminergic innervation is a characteristic feature of the prefrontal cortex in the mammalian brain.     

Crossed corticothalamic and thalamocortical connections of macaque prefrontal cortex

We have conducted a systematic comparison of the ipsilateral (uncrossed) and contralateral (crossed) thalamic connections of prefrontal cortex in macaque monkeys, using cortical implants of horseradish peroxidase pellets and tetramethyl benzidine histochemistry to demonstrate anterograde and retrograde thalamic labeling. Contrary to the prevailing belief that thalamocortical projections are entirely uncrossed, our findings indicate that a modest crossed projection to prefrontal cortex arises from the mesial thalamus, principally the anteromedial and midline nuclei. Also, while confirming that corticothalamic projections are bilateral, we found that the pattern of crossed projections differs from that of uncrossed projections. Projections to mesial thalamic nuclei, specifically to the anteromedial nucleus, the midline nuclei, and the magnocellular part of the mediodorsal nucleus are bilateral, the contralateral projection being nearly as dense as the ipsilateral projection. Projections to the parvicellular part of the mediodorsal and ventral anterior nuclei are also bilateral, but the contralateral projection is much weaker than the ipsilateral projection. Prefrontal projections to the reticular nucleus, medial pulvinar, suprageniculate nucleus, and limitans nucleus appear to be exclusively ipsilateral. These results indicate that prefrontal cortex has prominent bilateral and reciprocal connections with the nuclei of the mesial thalamic region. As this region of the diencephalon has been implicated by anatomical and behavioral studies in memory functions, our findings suggest that prefrontal cortex, through its connections with this region, may be involved in the bilateral integration of mnemonic systems.     

Calcium-binding protein distributions and fiber connections of the nucleus accumbens in the pigeon (Columba livia)

Until recently, the exact location of the avian nucleus accumbens within the basal forebrain had not been well established (Reiner et al. [2004] J Comp Neurol 473:377-414). While a number of previous studies have shown afferents and efferents of the presumptive "nucleus accumbens," detailed and accurate connection patterns of this newly recognized area are still lacking. We set out to clarify these connections using small, localized injections of cholera toxin subunit B and biotinylated dextran amine directly into the nucleus. In order to increase the accuracy of tracer injections into target sites, we first conducted a systematic comparison of three calcium-binding proteins, namely, parvalbumin, calretinin, and calbindin, to characterize the nucleus accumbens and ascertain its boundaries. The results showed that the avian and mammalian nucleus accumbens had remarkable hodological similarities, including the connections with the hippocampus, amygdala, ventral pallidum, lateral hypothalamus, and ventral tegmental area. However, the most significant aspect of the present study is that the avian nucleus accumbens had extensive reciprocal connections with medial pallial structures, the mammalian counterparts of which are unclear. Three implications of this finding are discussed. First, the avian medial pallium may correspond to part of the mammalian prefrontal cortex based on the connections with the nucleus accumbens. Second, the avian brain has a "limbic loop" involving the medial pallium, which also receives input from the avian equivalent of the mediodorsal thalamus. Third, the extensive connections between the accumbens and medial pallium just dorsal to it suggest a column-like organization of limbic-associated areas in the avian telencephalon.     

No deficit in total number of neurons in the prefrontal cortex in schizophrenics

The prefrontal cortex (PFC), defined as the cortical region which has the major reciprocal connections with the mediodorsal thalamic nucleus (MD), has often been implicated in schizophrenia. Morphometric studies have shown altered neuronal density and structure in parts of the PFC in schizophrenic brains. In addition, the MD and nucleus accumbens have shown a significant deficit in total neuron number. The purpose of the present study was to estimate the total neuron number in the PFC in schizophrenics and controls. Using a stereological design, the PFC was studied in eight brains from schizophrenic patients and 10 age-matched control brains. The bilateral average total number of neurons in the PFC was estimated to be 2.76 x 10(9) (CV=S.D./mean=0.15) in the schizophrenic brains whereas that of controls was a non-significantly different value of 3.11 x 10(9) (CV=0.22; P=0.23). Furthermore, no significant differences were found between the two groups in neuronal density (P=0.10) or volume of the PFC (P=0.49). It is of course possible that a neuronal deficit, which cannot be revealed when estimating the total global number of neurons in the whole PFC, might exist in a subregion of the PFC. In conclusion, uniform loss of neuronal soma in the PFC does not appear to constitute the neural substrate of the pathological process in schizophrenia.     

The volume of the mediodorsal thalamic nucleus in treated and untreated schizophrenics.

Reductions of 40% in total cell number and 25% in volume of the mediodorsal thalamic nucleus were recently reported in an unbiased neurostereological study of neuroleptic-treated schizophrenic patients. In order to investigate whether these results might be secondary to many years of treatment with neuroleptic drugs, eight brains from schizophrenics never treated with neuroleptics and eight controls were studied using the unbiased Cavalieri volume estimator. To compare left-right differences in this region, twelve neuroleptic-treated schizophrenics and eleven control cases were compared. The brains used for the left-right comparison study and five of 20 used for comparison of treated and untreated brain volumes have been used in an earlier study. The mediodorsal thalamus volume was reduced by 31% in untreated schizophrenics and by 22% in neuroleptic-treated schizophrenics. No differences were found in mean total volume of the left and right mediodorsal thalamus in brains from controls nor from schizophrenics. A major difference exists with respect to time of fixation in controls (12 years) and untreated schizophrenics (39 years) that makes shrinkage differences a possible confounding variable. The results suggest that the consistent reduction in number of neurons in the mediodorsal thalamic nucleus are not secondary to prolonged treatment with neuroleptic drugs and that asymmetry in this specific brain region is not a feature of the schizophrenia-afflicted brain.     

Sources of presumptive glutamatergic/aspartatergic afferents to the mediodorsal nucleus of the thalamus in the rat.

The distribution of presumptive glutamatergic and/or aspartatergic neurons retrogradely labeled following injections of 3HD-aspartate into the mediodorsal nucleus of the thalamus (MD) in the rat was compared to the distribution of neurons labeled by comparable injections of the nonspecific retrograde tracer wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Cells retrogradely labeled by WGA-HRP were found in the prefrontal and agranular insular cortices; in forebrain structures such as the amygdaloid complex, the piriform cortex, the ventral pallidum and the reticular nucleus of the thalamus; and in several different parts of the brainstem, such as the superior colliculus, central grey, and substantia nigra, pars reticulata. Some, but not all, of these projections are presumably glutamatergic and/or aspartatergic. The projections to MD from the prefrontal and agranular insular cortices are well labeled with 3H-D-aspartate, as are projections from the anterior cortical amygdaloid nucleus. Projections from the superior colliculus to the lateral portion of MD also label with this tracer. However, other forebrain and brainstem projections to MD are not labeled with 3H-D-aspartate, and apparently do not use glutamate or aspartate as a neurotransmitter. These include the projections from the basal and accessory basal amygdaloid nuclei, as well as possibly GABAergic projections from the ventral pallidum and the substantia nigra, pars reticulata. A small fraction of the cells in the piriform cortex that project to MD label with 3H-D-aspartate, suggesting that this projection may be heterogeneous. In other experiments, presumptive GABAergic projections to MD were studied by using 3H-GABA as a retrograde tracer. Although in these cases the thalamic reticular nucleus is well labeled, the ventral pallidum and the substantia nigra, pars reticulata are only poorly labeled. Pallidal projections to the ventromedial thalamic nucleus (VM), which are likely to be GABAergic, were also studied with this technique. After injections of 3H-GABA into VM, only a few cells in the substantia nigra, pars reticulata, or entopeduncular nucleus were labeled. This result suggests 3H-GABA has limited usefulness as a transmitter-specific retrograde tracer.     

Afferent connections of the striatum and the nucleus accumbens in the lizard Gekko gecko

The afferent connections of the striatum and the nucleus accumbens of the lizard Gekko gecko were studied with retrograde tracing by means of horseradish peroxidase and Fluoro-Gold and with anterograde tracing by means of Phaseolus vulgaris leukoagglutinin. The striatum receives projections from the cortex, the dorsal ventricular ridge, the lateral amygdaloid nucleus, the globus pallidus, the anterior peduncular nucleus, the ventral tegmental area and substantia nigra, the area ventral to the substantia nigra, and the dorsal thalamus. The nucleus accumbens is projected upon by the cortex, the diagonal band, the ventral pallidum, the lateral preoptic area, the ventral tegmental area, and the dorsal thalamus. The source of the cortical projection to the striatum and the nucleus accumbens is a longitudinal zone in the dorsal cortex that, rostrally in the hemisphere, is located medially and, more caudally, in its middle one third. The medial and rostrolateral areas of the dorsal ventricular ridge each project to the striatum in a vertical zone. The fibers from the caudolateral area of the ridge end in two oblique bands located parallel to the border between the dorsal ventricular ridge and the striatum. The pathways from the mesencephalic tegmentum to the striatum and the nucleus accumbens show a medial to lateral topography. This is similar to the situation in birds, but contrary to that in mammals in which these pathways are extensively interconnected. The specific sensory nuclei of the dorsal thalamus were found to project not only to the dorsal ventricular ridge, but also, and in a topographical fashion, to the striatum. The dorsomedial thalamic nucleus, which innervates the dorsal ventricular ridge, has additional projections to the striatum and the nucleus accumbens. This projection pattern is similar to that of the intralaminar thalamic nuclei of birds and mammals.     

The ventral pallidal projection to the mediodorsal thalamus: a study with fluorescent retrograde tracers and immunohistofluorescence

We have examined rat basal forebrain projections to the mediodorsal thalamic nucleus (MD) by making injections of retrogradely transported fluorescent tracers into the MD. Additionally, in some animals, we also stained sections for glutamate decarboxylase (GAD) by the indirect fluorescent antibody technique. Our results demonstrate that the following basal forebrain areas project to the MD: lateral orbital cortex, agranular insular cortex superficial to claustrum, primary olfactory cortex, diagonal band nuclei, ventral pallidum, and amygdala. A large number of labeled cells are present in the olfactory tubercle, and these cells are almost without exception located in dense GAD-positive ventral pallidal areas rather than in striatal regions of the tubercle. This ventral pallidal projection to the MD strengthens the concept of a ventral striatal-pallidal system in parallel to the classic striatal-pallidal system which projects to the ventral thalamus. These results are also discussed in relationship to the olfactory system.     

Efferent projections of the infralimbic (area 25) region of the medial prefrontal cortex in the rat: an anterograde tracer PHA-L study

The efferent projections of the infralimbic region (IL) of the medial prefrontal cortex of the rat were examined by using the anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L). Major targets of the IL were found to include the agranular insular cortex, olfactory tubercle, perirhinal cortex, the whole amygdaloid complex, caudate putamen, accumbens nucleus, bed nucleus of the stria terminalis, midline thalamic nuclei, the lateral preoptic nucleus, paraventricular nucleus, supramammillary nucleus, medial mammillary nucleus, dorsal and posterior areas of the hypothalamus, ventral tegmental area, central gray, interpeduncular nucleus, dorsal raphe, lateral parabrachial nucleus and locus coeruleus. Previously unreported projections of the IL to the anterior olfactory nucleus, piriform cortex, anterior hypothalamic area and lateroanterior hypothalamic nucleus were observed. The density of labeled terminals was especially high in the agranular insular cortex, olfactory tubercle, medial division of the mediodorsal nucleus of the thalamus, dorsal hypothalamic area and the lateral division of the central amygdaloid nucleus. Several physiological and pharmacological studies have suggested that the IL functions as the 'visceral motor' cortex, involved in autonomic integration with behavioral and emotional events. The present investigation is the first comprehensive study of the IL efferent projections to support this concept.     

Lesions of the dorsomedial nucleus of the thalamus, medial prefrontal cortex and pedunculopontine nucleus: effects on locomotor activity mediated by nucleus accumbens-ventral pallidal circuitry

A GABAergic nucleus accumbens-ventral pallidum projection is believed to serve as the critical first-order accumbens efferent pathway underlying the behavioral expression of mesolimbic dopamine (DA) activity in the rat. In a series of experiments, we studied the effects of lesions of several ventral pallidal efferent terminal regions on the rat locomotor response to apomorphine following 6-hydroxydopamine denervation of the nucleus accumbens. Lesions of the dorsomedial nucleus of the thalamus (DMT), but not the medial prefrontal cortex or the predunculopontine nucleus, significantly depressed the 'supersensitive' locomotor response to apomorphine. Lesions of the DMT did not depress baseline locomotion, but did diminish the locomotor activation produced by intracerebral injection of the gamma-aminobutyric acid antagonist picrotoxin into the ventral pallidum. These results suggest that accumbens-pallidothalamic circuitry plays a crucial role in translating the effects of mesolimbic DA activity to lower motor circuitry responsible for locomotor behavior in the rat.     

Circuits formultisensory integration and attentional modulation through the prefrontal cortex and the thalamic reticular nucleus in primates

Converging evidence from anatomic and physiological studies suggests that the interaction of high-order association cortices with the thalamus is necessary to focus attention on a task in a complex environment with multiple distractions. Interposed between the thalamus and cortex, the inhibitory thalamic reticular nucleus intercepts and regulates communication between the two structures. Recent findings demonstrate that a unique circuitry links the prefrontal cortex with the reticular nucleus and may underlie the process of selective attention to enhance salient stimuli and suppress irrelevant stimuli in behavior. Unlike other cortices, some prefrontal areas issue widespread projections to the reticular nucleus, extending beyond the frontal sector to the sensory sectors of the nucleus, and may influence the flow of sensory information from the thalamus to the cortex. Unlike other thalamic nuclei, the mediodorsal nucleus, which is the principal thalamic nucleus for the prefrontal cortex, has similarly widespread connections with the reticular nucleus. Unlike sensory association cortices, some terminations from prefrontal areas to the reticular nucleus are large, suggesting efficient transfer of information. We propose a model showing that the specialized features of prefrontal pathways in the reticular nucleus may allow selection of relevant information and override distractors, in processes that are deranged in schizophrenia.     

Glutamate and aspartate immunoreactive neurons of the rat basolateral amygdala: Colocalization of excitatory amino acids and projections to the limbic circuit

The basolateral amygdala has projections to several structures that take part in the limbic cortico-striato-pallido-thalamic circuit, including the prefrontal cortex, ventral striatum, and mediodorsal thalamic nucleus. The present investigation used a technique that combines retrograde tract tracing with immunohistochemistry for glutamate and aspartate to determine if amygdaloid neurons projecting to different targets in the limbic circuit can be distinguished on the basis of their content of excitatory amino acids. Cell counts revealed that at least 85–95% of the neurons in the basolateral nucleus projecting to the prefrontal cortex or ventral striatum were pyramidal cells that exhibited glutamate or aspartate immunoreactivity. Colocalization studies indicated that 94–100% of aspartate-immunoreactive neurons in the basolateral nucleus were also glutamate positive and that 92–94% of glutamate-immunoreactive neurons were also aspartate positive. A small number of glutamate-positive pyramidal neurons in the anterior subdivision of the cortical nucleus were found to project to the mediodorsal thalamic nucleus. However, the great majority of amygdaloid neurons with projections to the mediodorsal nucleus did not exhibit glutamate or aspartate immunoreactivity. The absence of glutamate and aspartate immunoreactivity in these cells suggests that these neurons do not use excitatory amino acids as neurotransmitters. The finding of high levels of glutamate and aspartate in basolateral amygdaloid neurons projecting to the prefrontal cortex and ventral striatum is consistent with previous reports indicating that these neurons may use excitatory amino acids as neurotransmitters, but is not a definitive criterion for this determination. © 1996 Wiley-Liss, Inc.     

Organization of thalamic projections to the ventral striatum in the primate

Although thalamic projections to the dorsal striatum are well described in primates and other species, little is known about thalamic projections to the ventral or “limbic” striatum in the primate. This study explores the organization of the thalamic projections to the ventral striatum in the primate brain by means of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and Lucifer yellow (LY) retrograde tracer techniques. In addition, because functional and connective differences have been described for the core and shell components of the nucleus accumbens in the rat and are thought to be similar in the primate, this study also explores whether these regions of the nucleus accumbens can be distinguished by their thalamic input. Tracer injections are placed in different portions of the ventral striatum, including the medial and lateral regions of the ventral striatum; the central region of the ventral striatum, including the dorsal part of the core of the nucleus accumbens; and the shell region of the nucleus accumbens. Retrogradely labeled neurons are located mainly in the midline nuclear group (anterior and posterior paraventricular, paratenial, rhomboid, and reuniens thalamic nuclei) and in the parafascicular thalamic nucleus. Additional labeled cells are found in other portions of the intralaminar nuclear group as well as in other thalamic nuclei in the ventral, anterior, medial, lateral, and posterior thalamic nuclear groups. The distribution of labeled cells varies depending on the area of the ventral striatum injected. All regions of the ventral striatum receive strong projections from the midline thalamic nuclei and from the parafascicular nucleus. In addition, the medial region of the ventral striatum receives numerous projections from the central superior lateral nucleus, the magnocellular subdivision of the ventral anterior nucleus, and parts of the mediodorsal nucleus. After injection into the lateral region of the ventral striatum, few labeled neurons are seen scattered in nuclei of the intralaminar and ventral thalamic groups and occasional labeled cells in the mediodorsal nucleus. The central region of the ventral striatum, including the dorsal part of the core of the nucleus accumbens, receives a limited projection from the midline thqlamic, predominantly from the rhomboid nucleus. It receives much smaller projections from the central medial nucleus and the ventral, anterior, and medial thalamic groups. The shell of the nucleus accumbens receives the most limited projection from the thalamus and is innervated almost exclusively by the midline thalamic nuclei and the central medial and parafascicular nuclei. The shell is distinguished from the rest of the ventral striatum in that it receives the fewest projections from the ventral, anterior, medial, and lateral thalamic nuclei. © 1995 Wiley-Liss, Inc.