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Connections of higher order visual relays in the thalamus: a study of corticothalamic pathways in cats.

Axonal markers injected into layers 5 and 6 of cortical areas 17, 18, or 19 labeled axons going to the lateral geniculate nucleus (LGN), the lateral part of the lateralis posterior nucleus (LPl), and pulvinar (P). Area 19 sends fine axons (type 1, Guillery [1966] J Comp Neurol 128:21-50) to LGN, LPl, and P, and thicker, type 2 axons to LPl and P. Areas 17 and 18 send type 1 axons to LGN, and a few type 1, but mainly type 2 axons to LPl and P. Type 1 and 2 axons from a single small cortical locus distribute to distinct, generally nonoverlapping parts of LP and P; type 1 axons have a broader distribution than type 2 axons. Type 2 axons, putative drivers of thalamic relay cells (Sherman and Guillery [1998] Proc Natl Acad Sci USA 95:7121-7126; Sherman and Guillery [2001] Exploring the thalamus. San Diego: Academic Press), supply small terminal arbors (100- to 200-microm diameter) in LPl and P, and then continue into the midbrain. Each thalamic type 2 arbor contains two terminal types. One, at the center of the arbor, is complex and multilobulated; the other, with a more peripheral distribution, is simpler and may contribute to adjacent arbors. Type 2 arbors from a single injection are scattered around and along "isocortical columns" in LPl, (i.e., columns that represent cells having connections to a common cortical locus). Evidence is presented that the connections and consequently the functional properties of cells in LP change along these isocortical columns. Type 2 driver afferents from a single cortical locus can, thus, be seen as representing functionally distinct, parallel pathways from cortex to thalamus.

Animals↗

Afferent projections to nucleus reuniens of the thalamus.

The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus and the major source of thalamic afferents to the hippocampus and parahippocampal structures. Nucleus reuniens has recently been shown to exert powerful excitatory actions on CA1 of the hippocampus. Few reports on any species have examined afferent projections to nucleus reuniens. By using the retrograde anatomical tracer Fluorogold, we examined patterns of afferent projections to RE in the rat. We showed that RE receives a diverse and widely distributed set of afferents projections. The main sources of input to nucleus reuniens were from the orbitomedial, insular, ectorhinal, perirhinal, and retrosplenial cortices; CA1/subiculum of hippocampus; claustrum, tania tecta, lateral septum, substantia innominata, and medial and lateral preoptic nuclei of the basal forebrain; medial nucleus of amygdala; paraventricular and lateral geniculate nuclei of the thalamus; zona incerta; anterior, ventromedial, lateral, posterior, supramammillary, and dorsal premammillary nuclei of the hypothalamus; and ventral tegmental area, periaqueductal gray, medial and posterior pretectal nuclei, superior colliculus, precommissural/commissural nuclei, nucleus of the posterior commissure, parabrachial nucleus, laterodorsal and pedunculopontine tegmental nuclei, nucleus incertus, and dorsal and median raphe nuclei of the brainstem. The present findings of widespread projections to RE, mainly from limbic/limbic-associated structures, suggest that nucleus reuniens represents a critical relay in the transfer of limbic information (emotional/cognitive) from RE to its major targets, namely, to the hippocampus and orbitomedial prefrontal cortex. RE appears to be a major link in the two-way exchange of information between the hippocampus and the medial prefrontal cortex.

Afferent Pathways↗

Functional impact of primary visual cortex deactivation on subcortical target structures in the thalamus and midbrain.

The functional relationships between the primary visual cortex and its major subcortical target structures have long been a subject of interest. We studied these relationships by using localized cooling deactivation to silence portions of primary visual cortex and measuring 2-deoxyglucose (2DG) uptake to assess neural activity in subcortical and midbrain targets. We focused analysis on the largest subcortical targets of primary visual cortex: the superior colliculus (SC), the dorsal lateral geniculate nucleus of the thalamus (dLGN), and the lateral division of the lateral posterior nucleus of the thalamus (LPL). We found that localized cooling of different regions of primary visual cortex caused specific decreases in 2DG uptake in target structures such that the location of 2DG decrease varied according to joint retinotopy, and the magnitude of the decreases in target structures was associated with the amount of cooled cortex. In addition, we found that the impact of cortical cooling was more profound on the SC than on the dLGN. The functional impact of cortical deactivations on the LPL was weak for small deactivations but approximated the impact on the SC when deactivations were large. We discuss these findings in terms of neural circuits and in terms of drivers and modulators.

Animals↗

Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets.

Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high ephrin expression in the MGN. In rewired ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets.

Animals↗

Retrograde analyses of spinothalamic projections in the macaque monkey: input to posterolateral thalamus.

The distribution of retrogradely labeled spinothalamic tract (STT) neurons was analyzed in macaque monkeys following variously sized, physiologically guided pressure or iontophoretic injections of cholera toxin subunit B (CTb) in order to determine whether different STT termination sites receive input selectively from different sets of STT cells. This report focuses on posterolateral thalamus, where prior anterograde tracing observations identified the posterior part of the ventromedial nucleus (VMpo) as the major projection target of lamina I STT neurons. Large injections in posterolateral thalamus labeled predominantly STT cells in lamina I throughout the spinal cord. In cases with medium-sized or small injections centered in VMpo, almost all labeled STT cells ( approximately 90%) were lamina I neurons. Small injections revealed a posteroanterior (foot to hand) somatotopographic organization consistent with that observed in prior anterograde tracing work; injections in posterior VMpo labeled primarily lumbosacral lamina I cells, whereas injections placed more anteriorly in VMpo labeled primarily cervical lamina I cells. These findings support the concept that VMpo is a primate lamina I spinothalamocortical relay nucleus important for pain, temperature, itch, muscle ache, sensual touch, and other interoceptive feelings from the body, and they provide strong evidence for the general hypothesis that the STT consists of several functionally and anatomically differentiable components.

Animals↗

Species differences in mechanosensory projections from the mouth to the ventrobasal thalamus.

To determine whether the largely ipsilateral, inverted representation of mouth parts in the ventrobasal thalamus of sheep was unique to that species or an expansion of a general mammalian pattern, the corresponding thalamic projections were mapped electrophysiologically in a selected series of mammals (oppossums, agoutis, squirrel monkeys, cats, raccoons, and sheep) representing major branches of evolution among therian mammals. In mapping, tungsten microelectrodes were used to record multi-unit discharges in the thalamus in response to mechanical stimulation of oral surfaces. The pattern of projections seen in sheep is not a general mammalian pattern; there is extensive variability among mammals in the laterality and internal orgainzation of the projections from the mouth. In spite of the great variability, the results suggest an hypothesis concerning phylogenetic trends: descendants of palaeoryctoid insectivores (cats, raccoons, and sheep in our sample) have extensive ipsilateral projections from the mouth, in other therian mammals (opossums, agoutis, and squirrel monkeys in our sample) the ipsilateral component is small or absent.

Animals↗

Afferent connections to the amygdaloid complex of the rat and cat. I. Projections from the thalamus.

By the use of the retrograde transport of horseradish peroxidase (HRP), the projections from the thalamus to the amygdala were investigated in the rat and cat, with main emphasis on the former species. HRP was injected stereotactically by microiontophoresis in the various amygdaloid nuclei. Several control procedures including the use of different approaches for the introduction of the micropipette were undertaken to eliminate the possibility of misinterpretation due to uptake of the protein by adjacent structures or fibers en passant. The paraventricular and paratenial nuclei of the thalamus were found to project throughout the entire amygdaloid complex. The medial geniculate complex and the basal nucleus of the ventromedial complex (the thalamic taste relay) mainly project to the centromedial part of the amygdala. The basolateral nucleus is the main recipient of a hitherto undescribed bilateral thalamo-amygdaloid pathway originating in the interanteromedial nucleus. The parafasciculare nucleus projects to the central nucleus of the amygdala; in the cat mainly to the lateral subdivision of the central nucleus. The findings are discussed in relation to previous anatomical and electrophysiological studies centered on the amygdaloid complex. Special reference is made to the possible role of the thalamo-amygdaloid connections in the conveyance of sensory information to the amygdala.

Afferent Pathways↗

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.

Animals↗

The somatotopic organization of the ventroposterior thalamus of the squirrel monkey, Saimiri sciureus.

Multiunit microelectrode mapping techniques were used to investigate the organization of the somatosensory thalamus in squirrel monkeys. Receptive fields and response characteristics were determined for closely spaced recording sites along arrays of electrode penetrations that passed through the ventral thalamus dorsoventrally, rostrocaudally, or lateromedially. The results were related to thalamic architecture and led to the following conclusions: (1) A large, single, systematic representation of the body surface occupied most or all of the ventroposterior nucleus, VP. The nucleus was further defined by a distinct cytoarchitectonic appearance, produced by densely packed, deeply stained neurons. (2) Recording sequences in VP were characterized by (a) abrupt shifts in receptive field locations over short recording distances indicating that the electrode had crossed discontinuities or folds in the representation, (b) long sequences of overlapping receptive fields indicating regions of continuous representation and the maintenance of adjacency in the map, and (c) similar receptive field locations for sites along the trajectory of a penetration indicating regions of isorepresentation. Major somatotopic discontinuities were associated with crossing narrow cell-poor laminae that partially divided VP into subnuclei related to the hand, foot, trunk, and tail in lateral VP and the face in medial VP. Somatotopic discontinuities occurred for electrode penetrations in all three planes, but discontinuities were greater and more frequent for lateromedial electrode penetrations. Lines of isorepresentation and gradual change were most extensive in the rostrocaudal and dorsoventral planes. We hypothesize that the disruptions, regions of isorepresentation, and regions of gradual change result from the thickening, splitting, and folding of a two-dimensional representation of the skin surface to occupy a three-dimensional volume. (3) The magnifications of various skin surfaces in VP were variable so that some skin surfaces, especially the tips of the digits, occupied relatively large portions of the nucleus, while other skin surfaces such as the trunk activated little tissue. It appeared that regions of isorepresentation varied in extent according to magnification factor and position in the map. (4) Within VP, neurons could be classified as slowly adapting or rapidly adapting to maintained skin indentation. Each type of neuron formed small groups or clusters in the nucleus so that several successive recording sites typically encountered one type before a sequence of the other type was observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

The organization of the lateral thalamus of the hooded rat.

Analysis of cytoarchitecture and connectivity showed that the lateral thalamus of the hooded rat is composed of eight nuclei. An examination of the cytoarchitecture permitted the identification of seven cellular fields: nucleus suprageniculatus (sg), nucleus lateralis posterior pars caudomedialis (lpcm), nucleus lateralis posterior pars lateralis (lpl), nucleus lateralis posterior pars rostromedialis (lprm), intramedullary area (ima), nucleus lateralis dorsale pars ventrolateralis (ldvl), and nucleus lateralis dorsale pars dorsomedialis (lddm). An analysis of the connectivity showed that lpl is further divisible into a rostral (lplr) and a caudal (lplc) sector, bringing the total number of nuclei to eight. Nucleus suprageniculatus, the most caudal element of the lateral thalamus, is composed of medium to large, fusiform, and multipolar neurons. It contains a terminal field of the projection of the superficial layers of the ipsilateral superior colliculus. Nucleus lpcm, found rostrolateral to sg, is loosely packed with large multipolar neurons. A terminal field of the superficial layers of the superior colliculus of both sides fits precisely within its cytoarchitectural boundaries. Nucleus lpl, a long cellular territory found lateral to lpcm, extends from the caudal pole of the dorsal lateral geniculate nucleus to the caudal pole of ldvl and contains round cells which are smaller and more densely packed than those of lpcm. Its caudal portion (lplc) contains another terminal field of the ipsilateral superior colliculus while its rostral portion (lplr) contains a terminal field of the projection of Area 17. Area 18 also projects to lplr, whereas Area 18a projects to both lplr and lplc. The intramedullary area, which occupies the fibrous zone between lpl and the dorsal lateral geniculate nucleus, contains round and fusiform neurons and is innervated by Area 18a. Nucleus lprm, situated medial to lpl, is characterized by round neurons which are frequently found in clusters. It is innervated by Areas 17, 18, and 18a. Nucleus ldvl is evenly packed with moderately large, polygonal cells and contains the complete terminal fields of both Areas 17 and 18. It also receives inputs from Area 18a. Finally, lddm, tightly packed with small, round cells and lying medial to ldvl, receives inputs from Area 4.

Animals↗

Morphology of physiologically identified thalamocortical relay neurons in the rat ventrobasal thalamus.

The anatomical structure of physiologically identified neurons of the rat ventrobasal thalamus was studied in order to determine if there are morphologically distinct subsets of neurons that correlate with the somatosensory submodalities processed by these cells. Intracellular recordings were used to determine the modality and receptive field of a neuron, after which horseradish peroxidase was iontophoretically injected into the cell, allowing it to be histologically visualized. Computer-assisted measurements of the labeled cells were made to quantitatively analyze the dendritic structure. Cells were divided into physiological groups stimulated by whiskers, glabrous skin, furry skin, noxious stimulation, or joint rotation. Qualitatively, all cells appeared similar, with the same types of branching patterns. Dendritic spines and long, sinuous appendages were found on all distal dendrites. Quantitatively, no statistically significant differences in dendritic structure were found between functionally defined groups with the aid of a number of parameters, including a fitted dendritic ellipse. There was a weak correlation between somal cross-sectional area and receptive field size, suggesting larger cells processed larger receptive fields. In summary, the ventrobasal thalamus of the rat, in contrast to that of higher mammals, appears to contain only one major cell type and to have a very simple neuronal circuitry.

Action Potentials↗

Evidence for parallel processing in the frog's auditory thalamus.

We have conducted anatomical and physiological experiments to investigate the functional organization of the dorsal thalamus in the northern leopard frog (Rana pipiens pipiens). Our studies provide evidence for parallel auditory processing at this level of the frog's brain. Acoustically evoked potentials were recorded from the posterior and central thalamic nuclei and several differences in sound-evoked activity were noted between them: the amplitude of acoustically evoked potentials (AEPs), in response to a standard search stimulus, was always greater in the central, as opposed to the posterior, nucleus; the posterior, but not central, nucleus exhibited the phenomenon of nonlinear summation when 350-Hz and 1,700-Hz tones were presented simultaneously rather than individually; and the central, but not posterior, nucleus showed selectivity for the repetition rate of pulsed sound signals. The posterior and central thalamic nuclei also possessed distinct innervation patterns as revealed by the HRP transport patterns arising from these structures. The central nucleus was reciprocally connected with the major auditory relay stations along the frog's central auditory pathway including the superior olive, nucleus of the lateral lemniscus, and the torus semicircularis. Major projections to the lateral thalamic nucleus, ventral hypothalamus, and the telencephalic striatal complex were also observed. The posterior nucleus, on the other hand, established reciprocal connections primarily with the medial reticular nucleus, ventral midbrain tegmentum, and structures constituting of the ventral thalamic nuclei, particularly the nucleus of Bellonci. Thus, time and frequency cues contained within the species mating call, and conveying information concerning species identity, appear to be processed independently within the frog's thalamus with separate neural channels for each.

Animals↗

The origins of cholinergic and other subcortical afferents to the thalamus in the rat.

The origins of the cholinergic and other afferents of several thalamic nuclei were investigated in the rat by using the retrograde transport of wheat germ agglutinin conjugated-horseradish peroxidase in combination with the immunohistochemical localization of choline acetyltransferase immunoreactivity. Small injections placed into the reticular, ventral, laterodorsal, lateroposterior, posterior, mediodorsal, geniculate, and intralaminar nuclei resulted in several distinct patterns of retrograde labelling. As expected, the appropriate specific sensory and motor-related subcortical structures were retrogradely labelled after injections into the principal thalamic nuclei. In addition, other basal forebrain and brainstem structures were also labelled, with their distribution dependent on the site of injection. A large percentage of these latter projections was cholinergic. In the brainstem, the cholinergic pedunculopontine tegmental nucleus was retrogradely labelled after all thalamic injections, suggesting that it provides a widespread innervation to the thalamus. Neurons of the cholinergic laterodorsal tegmental nucleus were retrogradely labelled after injections into the anterior, laterodorsal, central medial, and mediodorsal nuclei, suggesting that it provides a projection to limbic components of the thalamus. Significant basal forebrain labelling occurred only with injections into the reticular and mediodorsal nuclei. Only injections into the reticular nucleus resulted in retrograde labelling of the cholinergic neurons in the nucleus basalis of Meynert. The results provide evidence for an organized system of thalamic afferents arising from cholinergic and noncholinergic structures in the brainstem and basal forebrain. The brainstem structures, especially the cholinergic pedunculopontine tegmental nucleus, appear to project directly to principal thalamic nuclei, thereby providing a possible anatomical substrate for mediating the well-known facilitory effects of brainstem stimulation upon thalamocortical transmission.

Acetylcholine↗

Quantitative Golgi study of anatomically identified subdivisions of motor thalamus in the rat.

A Golgi study of neurons in the ventroanterior-ventrolateral complex (VAL) and ventromedial (VM) nucleus in the dorsal thalamus of rats was performed. To facilitate the delineation of subdivisions of these nuclei, some animals received injections of horseradish peroxidase (HRP) into the afferent and efferent fields of VAL and VM, and alternate sections were processed for the histochemical detection of HRP. As an adjunct to subjective observations, a multivariate statistical analysis of morphometric variables was performed to provide an objective assessment of neuronal morphology. All Golgi-stained neurons in VAL and VM were tentatively identified as projection neurons; no cells with morphological features commonly ascribed to thalamic interneurons were impregnated. Four classes of morphologically distinct neurons were identified in VAL. Type 1 neurons, the most commonly impregnated cell, were found throughout the extent of VAL and resembled "tufted" or "multipolar bush" neurons described previously in many thalamic nuclei. The remaining three neuronal types differed in a number of morphometric parameters and were differentially distributed throughout VAL. Type 2 neurons, distinguished in part by dendritic spine morphology and elongated bipolar dendritic fields, were found only in the rostral sector of the dorsal division of VAL (VALD). Type 3 neurons, characterized by a large and evenly distributed dendritic field, were situated in rostral VAL (all subdivisions). Type 4 neurons had small soma and dendritic dimensions and were located in the ventromedial aspect of the ventral division of VAL (VALV) adjacent to VM. In contrast, the vast majority of neurons in VM were considered to be a single morphological class (similar in form to type 4 neurons in VAL), although a rarely impregnated second type of neuron was also observed. The apparent scarcity of interneurons in VAL and VM is consistent with previous evidence that the synaptic organization of motor thalamus in the rat is markedly different from that of higher-order mammals. Speculation about the functional attributes of the neuronal types in VAL and VM is necessarily restricted to considerations of afferent and efferent relations, since "motor modality" functions of neurons in these nuclei have yet to be elucidated.

Animals↗

Calcitonin gene-related peptide immunoreactivity in the visceral sensory cortex, thalamus, and related pathways in the rat.

It has been proposed that calcitonin gene-related peptide (CGRP) may serve as a major neuromodulator in visceral sensory pathways, but its exact role in the visceral sensory thalamus and cortex has not been determined. We therefore examined the distribution of CGRP-like immunoreactive (CGRPir) innervation of the insular cortex and the parvicellular division of the ventroposterior nucleus of the thalamus (VPpc) in the rat by using immunohistochemistry for CGRP combined with retrograde transport of the fluorescent dye fluoro-gold. Modest numbers of CGRPir fibers were distributed in the dysgranular and agranular insular cortex, but few were observed in the granular insular cortex. The density of CGRPir innervation increased caudally along the rhinal fissue and was considerably greater in the perirhinal cortex. When fluoro-gold was injected into the insular cortex numerous retrogradely labeled neurons were seen in the VPpc, but few of these were CGRPir. Retrogradely labeled CGRPir neurons were, however, seen in the ventral lateral and medial parabrachial (PB) subnuclei. Injection of fluoro-gold into the perirhinal cortex (which is just caudal to the insular cortex along the rhinal fissure) resulted in many retrogradely labeled CGRPir neurons in the posterior thalamic region, including the subparafascicular, the lateral subparafascicular, and the posterior intralaminar nuclei. The VPpc was heavily innervated by CGRPir fibers but contained few CGRPir cell bodies. Injection of fluoro-gold into the VPpc resulted in many retrogradely labeled CGRPir neurons in the external medial PB subnucleus bilaterally, but with a contralateral predominance. Smaller numbers of retrogradely labeled CGRPir neurons were also observed in the ventrolateral PB subnucleus, bilaterally with an ipsilateral predominance. These results suggest that CGRP may be a neuromodulator in the ascending visceral sensory pathways from the PB to the VPpc and the insular cortex, but not between the latter two structures.

Animals↗

Serotoninergic and noradrenergic projections to the ventral posterolateral nucleus of the monkey thalamus.

In the present study, serotoninergic and noradrenergic varicosities were identified in the ventral posterolateral nucleus of the macaque monkey. Monoaminergic neurons projecting to the ventral posterolateral nucleus of the thalamus were identified by using retrograde labeling with horseradish peroxidase combined with immunocytochemical staining for serotonin or dopamine-beta-hydroxylase. The midbrain nucleus raphe dorsalis was the major site of origin for neurons providing a serotoninergic projection to the ventral posterolateral nucleus. A few retrogradely labeled serotonin-containing neurons were also observed in the central superior and the raphe pontis nuclei. Noradrenergic cells with projections to the thalamus were primarily located in the nucleus locus coeruleus with some projection neurons in the nucleus subcoeruleus, and the A5 catecholamine cell group of the pons.

Animals↗

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.

Animals↗

Cholinergic innervation of the human thalamus: dual origin and differential nuclear distribution.

The cholinergic innervation of the human thalamus was studied with antibodies against the enzyme choline acetyltransferase (ChAT) and nerve growth factor receptor (NGFr). Acetylcholinesterase histochemistry was used to delineate nuclear boundaries. All thalamic nuclei displayed ChAT-positive axons and varicosities. Only the medial habenula contained ChAT-positive perikarya. Some intralaminar nuclei (central medial, central lateral, and paracentral), the reticular nucleus, midline nuclei (paraventricular and reuniens), some nuclei associated with the limbic system (anterodorsal nucleus and medially situated patches in the mediodorsal nucleus) and the lateral geniculate nucleus displayed the highest density of ChAT-positive axonal varicosities. The remaining sensory relay nuclei and the nuclei interconnected with the motor and association cortex displayed a lower level of innervation. Immunoreactivity for NGFr was observed in cholinergic neurons of the basal forebrain but not in cholinergic neurons of the upper brainstem. The contribution of basal forebrain afferents to the cholinergic innervation of the human thalamus was therefore studied with the aid of NGFr-immunoreactive axonal staining. The anterior intralaminar nuclei, the reticular nucleus, and medially situated patches in the mediodorsal nucleus displayed a substantial number of NGFr-positive varicose axons, presumably originating in the basal forebrain. Rare NGFr-positive axonal profiles were also seen in many of the other thalamic nuclei. These observations suggest that thalamic nuclei affiliated with limbic structures and with the ascending reticular activating system are likely to be under particularly intense cholinergic influence. While the vast majority of thalamic cholinergic input seems to come from the upper brainstem, the intralaminar and reticular nuclei, and especially medially situated patches within the mediodorsal nucleus also appear to receive substantial cholinergic innervation from the basal forebrain.

Acetylcholine↗