Projections of the globus pallidus and adjacent structures: An autoradiographic study in the monkey

Because the globus pallidus gives rise to the principal efferent system of the corpus striatum and is traversed by several fibers systems, attempts were made to study the projections of its cells by autoradiographic technics. Tritiated amino acids (L-leucine, L-proline and L-lysine) were injected into: (1) the medial pallidal segment (MPS), (2) the MPS and the substantia innominata (SI), (3) portions of the MPS and the lateral pallidal segment (LPS) and (4) parts of the putamen. Cells labeled by injections of the MPS transported isotope to thalamic nuclei (ventral anterior, VApc, ventral lateral, VLo and VLm, and the centromedian, CM), the pedunculopontine nucleus (PPN), and the lateral habenular nucleus (Hbl). Labeled cells of the MPS and SI transported isotope to: (1) thalamic nuclei (VLo, VLm and CM), (2) PPN, (3) Hbl, (4) lateral and posterior regions of the hypothalamus, and (5) extensive dorsal regions of the substantia nigra (SN). Comparisons of label transported from uptake of isotope by cells of the MPS, and cells of both pallidal segments, suggest that the LPS projects fibers only to the subthalamic nucleus (STN). Not all regions of the STN appear to receive fibers from the LPS. Selectively labeled neurons of the putamen transport isotope to broad regions of both pallidal segments and to the pars reticulata of the SN. This study suggests that cells of the MPS project profusely and topographically to: (1) the rostral ventral tier thalamic nuclei (VApc, VLo and VLm), (2) lateral portions of CM, and (3) the PPN. Fibers of the lenticular fasciculus appear to terminate preferentially in VLo. Cells in sublenticular portions of SI, and those extending into the medullary laminae of the pallidum, appear to project to: (1) HBl via the stria medullaris, (2) the pars compacta of SN, (3) lateral and posterior regions of the hypothalamus, and (4) the so-called nucleus of the ansa lenticularis. Some fibers from cells of SI appear to join the dorsal stria terminalis, but none enter the inferior thalamic peduncle and none project to any part of the dorsomedial nucleus of the thalamus.     

Interconnections and organization of pallidal and subthalamic nucleus neurons in the monkey

Attempts were made to determine the topographic organization of subthalamopallidal and pallidosubthalamic projections in order to evaluate interconnections between the subthalamic nucleus (STN) and the globus pallidus (GP). In a series of monkeys retrograde and anterograde axoplasmic transport technics were used to explore these interconnections. Small volumes of horseradish peroxidase (HRP) were injected selectively into: (1) the medial pallidal segment (MPS), (2) the rostral division of the lateral pallidal segment (LPS, rostral to the medial medullary lamina of the GP), and (3) the central division of the LPS (lateral to the medial medullary lamina of GP). Retrograde transport of the enzyme to cells in the STN indicated that: (1) cells in the medial and caudal third of the nucleus project predominantly to the MPS, (2) cells in medial portions of the middle third of the nucleus project predominantly to the rostral division of the LPS, and (3) cells in central portions of the rostral two-thirds of the nucleus project to the central division of the LPS, with the largest contribution derived from rostral regions of the nucleus. An inverse dorsoventral topographical relationship appears to exist between cells in the STN and axonal terminations in the LPS, in that cells in dorsal regions of the STN project to ventral regions of the LPS, while cells in ventral regions of the STN project to dorsal regions of the LPS. No similar relationship could be established between the STN and the MPS because of its smaller size. Cells in the lateral third of the STN do not project terminals to the MPS or the rostral or central divisions of the LPS. It is suggested that cells in the lateral third of the STN project to the caudal division (caudal to the medial medullary lamina of the GP) of the LPS. A small number of cells in the pedunculopontine nucleus project to the MPS. Pallidosubthalamic projections were determined from autoradiographs based upon injections of [³H] amino acids into the MPS, the LPS, and both segments of the GP. Selective labeling of cells in the MPS resulted in no transport of isotope to any part of the STN. Labeling of cells in the rostral division of the LPS resulted in transport of isotope to: (1) the medial two-thirds of the rostral part of the STN and (2) the central region of the middle third of the nucleus. Cells in the central division of the LPS projected fibers to the lateral third of the STN throughout most of its rostrocaudal extent. Even though the STN is a relatively small nucleus, it appears organized into afferent and efferent portions with respect to the GP. Subthalamopallidal fibers originate mainly from the medial two-thirds of the STN and are topographically organized; cells in specific and separate locations within the STN project to wellcircumsumscribed terminations within either the MPS or the LPS. These data do not support the thesis that major axonal collaterals of STN neurons supply both pallidal segments, although this possibility cannot be excluded. Subthalamic neurons projecting to the MPS arise from cells in medial and caudal parts of the nucleus that do not receive projections from any part of the GP or from the cerebral cortex. Pallidosubthalamic projections derived from the rostral and central divisions of the LPS terminate in distinctive loci within the STN. Comparisonsof these regions of termination with those that give rise to subthalamopallidal projections suggest that direct reciprocal connections between the STNand the LPS must be partial. If functional reciprocal connections exist between STN and the two major segments of the GP, these are not on a point forpoint basis and local interneurons must be involved.     

Topographical projections from the thalamus, subthalamic nucleus and pedunculopontine tegmental nucleus to the striatum in the Japanese monkey, Macaca fuscata.

Topographical projections from the thalamus, subthalamic nucleus (STN) and pedunculopontine tegmental nucleus (PPN) to the striatum were examined in the Japanese monkey (Macaca fuscata) by using the retrograde axonal transport technique of WGA-HRP (wheat germ agglutinin-conjugated horseradish peroxidase). After WGA-HRP injection in the head of the caudate nucleus (CN) or putamen (Put), labeled neuronal cell bodies in the thalamus were distributed mainly in the nucleus ventralis anterior (VA)-nucleus ventralis lateralis (VL) complex and the nucleus centrum medianum (CM)-nucleus parafascicularis (Pf) complex, and additionally in the paraventricular, parataenial, rhomboid, reuniens, centrodorsal, centrolateral, paracentral, and centromedial nuclei. The data indicated that the pars principalis of VA (VApc) projected mainly to CN and additionally to Put, and that the pars magnocellularis of VA (VAmc) or pars oralis of VL (VLo) projected selectively to CN or Put, respectively. It was also indicated that CM projected to the middle and caudal parts of Put, while Pf projected to CN and the rostral part of the Put. The data further indicated that the dorsomedial, ventromedial, or lateral part of CM projected respectively to the dorsolateral, ventromedial, or intermediate part of Put, and that the medial or lateral part of Pf projected respectively to the medial or lateral part of the head of CN. Direct projections from STN and PPN to the striatum were confirmed. The subthalamostriatal projections showed a mediolateral topography. The PPN was shown to project bilaterally to the striatum with an ipsilateral predominance.     

Direct cortical projections to the parabrachial nucleus in the cat

Direct projections from the cerebral cortex to the parabrachial nucleus in the cat were examined by the horseradish peroxidase (HRP)method. When HRP was injected into the parabrachial nucleus, retrogradely labeled neuronal cell bodies were seen, bilaterally with an ipsilateral predominance, mainly in the orbital gyrus, the lateral bank of the presylvian sulcus, and a restricted region in the infralimbic cortex on the medial surface of the frontal lobe (stereotaxic coordinates; Fr: 22, L: 1, H: -1); all labeled neurons were in deep pyramidal cell layer. After injecting HRP conjugated to wheat germ agglutinin (WGA-HRP) into the cortical regions where retrogradely labeled neurons were found after injecting HRP into the parabrachial nucleus, anterogradely labeled cortical fibers were traced to the parabrachial nucleus. Corticoparabrachial fibers originating from the orbital gyrus and the lateral bank of the presylvian sulcus ran ipsilaterally through the internal capsule and the cerebral peduncle down to the lower brainstem, whereas those from the infralimbic cortex coursed down ipsilaterally through the medial forebrain bundle. These cortical fibers to the parabrachial nucleus were distributed bilaterally with an ipsilateral predominance. Cortical fiber terminals in the parabrachial nucleus were topographically arranged: Corticoparabrachial fibers from the lateral bank of the presylvian sulcus ended most massively in the dorsal part of the lateral parabrachial nucleus. Corticoparabrachial fibers from the orbital gyrus ended most heavily in the medial parabrachial nucleus and less heavily in the lateral parabrachial nucleus. Corticoparabrachial fibers from the infralimbic cortex ended mostly in the parabrachial regions surrounding the brachium conjunctivum.     

Cholinergic and non-cholinergic mesopontine tegmental neurons projecting to the subthalamic nucleus in the rat

The subthalamic nucleus (STN) receives cholinergic and non-cholinergic projections from the mesopontine tegmentum. This study investigated the numbers and distributions of neurons involved in these projections in rats using Fluorogold retrograde tracing combined with immunostaining of choline acetyltransferase and a neuron-specific nuclear protein. The results suggest that a small population of cholinergic neurons mainly in the caudoventral part of the pedunculopontine tegmental nucleus (PPN), approximately 360 neurons (≈ 10% of the total) in the homolateral and 80 neurons (≈ 2%) in the contralateral PPN, projects to the STN. In contrast, the number of non-cholinergic neurons projecting to the STN was estimated to be nine times as much, with approximately 3300 in the homolateral side and 1300 in the contralateral side. A large gathering of the Fluorogold-labeled non-cholinergic neurons was found rostrodorsomedial to the caudolateral PPN. The biotinylated dextran amine (BDA) anterograde tracing method was used to substantiate the mesopontine-STN projections. Injection of BDA into the caudoventral PPN labeled numerous thin fibers with small en-passant varicosities in the STN. Injection of BDA into the non-cholinergic neuron-rich area labeled a moderate number of thicker fibers with patches of aggregates of larger boutons. The densities of labeled fibers and the number of retrogradely labeled cells in the mesopontine tegmentum suggested that the terminal field formed in the STN by each cholinergic neuron is more extensive than that formed by each non-cholinergic neuron. The findings suggest that cholinergic and non-cholinergic mesopontine afferents may carry different information to the STN.     

Brainstem dopaminergic, cholinergic and serotoninergic afferents to the pallidum in the squirrel monkey

The retrograde tracer cholera toxin B subunit (CTb) was used in combination with immunohistochemistry for tyrosine hydroxylase (TH), calbindin D-28k (CaBP), choline acetyltransferase (ChAT) and 5-hydroxytryptamine (5-HT) to determine the distribution and relative proportion of brainstem chemospecific neurons that project to the pallidum in the squirrel monkey (Saimiri sciureus). Large injections of CTb involving both pallidal segments produce numerous retrogradely labeled neurons in the substantia nigra (SN), the pedunculopontine tegmental nucleus (PPN) and the dorsal raphe nucleus (DR). Labeled neurons are distributed uniformly in SN with a slight numerical increase at the junction between the pars compacta (SNc) and the ventral tegmental area (VTA). Retrogradely labeled neurons abound also in PPN, principally in its pars dissipata, whereas other CTb-labeled cells are scattered throughout the rostrocaudal extent of DR. After CTb injection involving specifically the internal pallidal segment (GPi), the same pattern of cell distribution is found in SN, PPN and DR, except that the number of retrogradely labeled cells is lower than after large pallidal complex injections. Approximately 70% of all CTb-labeled neurons in SNc-VTA complex display TH immunoreactivity, whereas 20% are immunoreactive for CaBP. About 39% of all retrogradely labeled neurons in PPN are immunoreactive for ChAT, whereas approximately 38% of the labeled neurons in DR display 5-HT immunoreactivity. Following CTb injection in the external pallidal segment (GPe), the number of labeled cells is much smaller than after GPi injection. The majority of CTb-labeled cells in SNc-VTA complex are located in the lateral half of SNc and approximately 93% of these neurons display TH immunoreactivity compared to 10% that are immunoreactive for CaBP; very few CTb-labeled cells occur in PPN. Retrogradely labeled cells in DR are located more laterally than those that projects to the GPi and about 25% of them are immunoreactive for 5-HT. These results suggest that, in addition to their action at striatal and/or nigral levels, the brainstem dopaminergic, cholinergic and serotoninergic neurons influence the output of the primate basal ganglia by acting directly upon GPi neurons.     

Neurons of origin and fiber trajectory of amygdalofugal projections to the medial preoptic area in Syrian hamsters

The amygdaloid neurons of origin and the trajectory of amygdaloid fibers to the medial preoptic area of the adult male Syrian hamster were identified by using horseradish peroxidase (HRP) histochemistry. After iontophoresis of HRP into the medial preoptic area, retrogradely labeled amygdaloid neurons were located in the dorsal and caudal parts of the medial amygdaloid nucleus and throughout the amygdalohippocampal area. No amygdaloid neurons were labeled after HRP applications confined to the most rostral portion of the medial preoptic area (anterior to the body of the anterior commissure). Following more caudal medial preoptic area injections (body of the anterior commissure to the suprachiasmatic nucleus) the distribution of retrogradely labeled cells in the medial amygdaloid nucleus and the amygdalohippocampal area revealed no topographic organization of the amygdalopreoptic connections. When amygdaloid neurons were labeled, the amygdalohippocampal area contained two to five times as many HRP-filled cells as the medial amygdaloid nucleus. Retrogradely transported HRP could be followed from the medial preoptic area to the amygdala through fibers in the dorsomedial quadrant of the stria terminalis. In addition, electrolytic lesions of the stria terminalis prior to iontophoresis of HRP into the medial preoptic area prevented retrograde transport to neurons in both the dorsocaudal medial amygdaloid nucleus and the amygdalohippocampal area. These results confirm earlier observations describing the location of autoradiographically labeled efferents from the medial amygdaloid nucleus to the medial preoptic area and provide new information about the restricted region within the medial amygdaloid nucleus from which these projections arise. They also suggest that, unlike the projections from the medial amygdaloid nucleus to the bed nucleus of the stria terminalis, the efferents to the medial preoptic area travel entirely in the stria terminalis.     

Retrograde labeling of rat dorsolateral septal nucleus neurons following intraseptal injections of WGA-HRP

Projection neurons in the rat dorsolateral septal nucleus (DLSN) were retrogradely labeled following intraseptal injection of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Injections of WGA-HRP centered in the medial septum (MS) and parts of the intermediate and ventrolateral subdivisions of the lateral septum retrogradely labeled only a few centrally scattered multipolar-shaped neurons. In contrast, injections placed in the nucleus of the diagonal band of Broca (DBB) consistently resulted in labeling of DLSN neurons of all sizes and shapes. Large injections in rostral DBB appeared to retrogradely label every DLSN neuron, while similar injections in caudal DBB only labeled neurons in restricted regions of the nucleus. A collection of small cells forming the ventricular border of caudal DLSN and a group of larger cells situated in the dorsolateral tip of rostral DLSN were consistently labeled following each DBB injection. The pattern of retrogradely labeled neurons in the DLSN appeared in a complementary fashion to that seen in the other lateral septal nuclei. Our findings support the conclusion that the DLSN is a morphologically heterogeneous nucleus consisting almost entirely of projection neurons. The pattern of retrograde labeling in the lateral septum suggests that these projection neurons may be topographically organized since distinct subpopulations of cells were labeled following different injections in the MS/DBB complex. © 1996 Wiley-Liss, Inc.     

Thalamocortical and thalamo-amygdaloid projections from the parvicellular division of the posteromedial ventral nucleus in the cat

Projections from the parvicellular division of the posteromedial ventral thalamic nucleus (VPMpc) of the cat were examined. After injection of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) into the VPMpc, both anterogradely labeled axon terminals and retrogradely labeled neuronal cell bodies were found ipsilaterally in three discrete regions of the cerebral cortex, i.e., in the orbital cortex, caudoventral part of the infralimbic cortex, and medial part of the fundus of the posterior rhinal sulcus (perirhinal area); in the subcortical regions, anterogradely labeled axon terminals were seen ipsilaterally in the rostrodorsal part of the lateral amygdaloid nucleus. Neuronal connections between these VPMpc-recipient regions were further verified by injecting WGA-HRP into each of the three cortical and the lateral amygdaloid regions. After injection of WGA-HRP into each of the three cortical regions, labeled neuronal cell bodies and axon terminals were seen ipsilaterally in the VPMpc, especially in its medial part, and in the other two of the three VPMpc-recipient cortical regions. In the rostrodorsal part of the lateral amygdaloid nucleus, both axon terminals and neuronal cell bodies were labeled after WGA-HRP injection into the perirhinal area, and only axon terminals were labeled after WGA-HRP injection into the orbital cortex, but no labeling was observed after WGA-HRP injection into the infralimbic cortex. After injection of WGA-HRP into the rostrodorsal portion of the lateral amygdaloid nucleus, both axon terminals and neuronal cell bodies were labeled ipsilaterally in the perirhinal area and the ectorhinal area, and only neuronal cell bodies were labeled ipsilaterally in the VPMpc (especially in its medial part) and orbital cortical region; no labeling was observed in the infralimbic cortex. The present results indicate that the VPMpc of the cat is connected reciprocally with the orbital, infralimbic, and perirhinal cortical regions on the ipsilateral side, that the three VPMpc-recipient cortical regions are reciprocally connected with each other, that the VPMpc sends fibers ipsilaterally to the rostrodorsal part of the lateral amygdaloid nucleus, which may relay information from the VPMpc to the perirhinal cortical area, and that the VPMpc-recipient area in the lateral amygdaloid nucleus receives cortical fibers from the orbital and perirhinal cortical regions.     

Efferent connections of the substantia innominata in the rat

The efferent connections of the substantia innominata (SI) were investigated employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The projections of the SI largely reciprocate the afferent connections described by Grove (J. Comp. Neurol. 277:315-346, '88) and thus further distinguish a dorsal and a ventral division in the SI. Efferents from both the dorsal and ventral divisions of the SI descend as far caudal as the ventral tegmental area, substantia nigra, and peripeduncular area, but projections to pontine and medullary structures appear to originate mainly from the dorsal SI. Within the amygdala and hypothalamus, which receive widespread innervation from the SI, the dorsal SI projects preferentially to the lateral part of the bed nucleus of the stria terminalis; the lateral, basolateral, and central nuclei of the amygdala; the lateral preoptic area; paraventricular nucleus of the hypothalamus; and certain parts of the lateral hypothalamus, prominently including the perifornical and caudolateral zones described previously. The ventral SI projects more heavily to the medial part of the bed nucleus of the stria terminalis; the anterior amygdaloid area; a ventromedial amygdaloid region that includes but is not limited to the medial nucleus; the lateral and medial preoptic areas; and the anterior hypothalamus. Modest projections reach the lateral hypothalamus, with at least a slight preference for the medial part of the region, and the ventromedial and arcuate hypothalamic nuclei. Both SI divisions appear to innervate the dorsomedial and posterior hypothalamus and the supramammillary region. In the thalamus, the subparafascicular, gustatory, and midline nuclei receive a light innervation from the SI, which projects more densely to the medial part of the mediodorsal nucleus and the reticular nucleus. Cortical efferents from at least the midrostrocaudal part of the SI are distributed primarily in piriform, infralimbic, prelimbic, anterior cingulate, granular and agranular insular, perirhinal, and entorhinal cortices as well as in the main and accessory olfactory bulbs. The cells of origin for many projections arising from the SI were identified as cholinergic or noncholinergic by combining the retrograde transport of WGA-HRP with histochemical and immunohistochemical procedures to demonstrate acetylcholinesterase activity or choline acetyltransferase immunoreactivity. Most of the descending efferents of the SI appear to arise primarily or exclusively from noncholinergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reciprocal connections between the medial preoptic area and the midbrain periaqueductal gray in rat: a WGA-HRP and PHA-L study.

The midbrain periaqueductal gray (PAG) participates in diverse functions such as analgesia, autonomic regulation, sexual behavior, and defense/escape responses. Anatomical studies of the circuits involved in such functions have largely focused on the connections of PAG with the medulla. Projections to PAG from forebrain structures are extensive, but their organization has received little attention. Previous anatomic studies indicate that the medial preoptic area (MPO), involved in a variety of physiological and behavioral functions, is a major source of afferent input to the periaqueductal gray. Here, we have examined the topography of reciprocal connections between these two structures in the rat by using wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) and Phaseolus vulgaris leucoagglutinin (PHA-L). Multiple WGA-HRP injections at several rostrocaudal levels of PAG retrogradely labeled large numbers of neurons in the medial preoptic area; labeled cells were primarily located in the medial preoptic nucleus, the median preoptic nucleus, and the region lateral to the medial preoptic nucleus. The distribution of labeled cells shifted medially to laterally along the rostral to caudal axis of the medial preoptic area. Rostrally, there was selective retrograde labeling in the central and lateral divisions of medial preoptic nucleus, whereas caudally, labeled cells were primarily located only in the lateral subdivision of medial preoptic nucleus. Tracer injections in PAG also produced strong anterograde labeling in MPO. WGA-HRP and PHA-L injections in the medial preoptic area resulted in dense anterograde labeling along the entire rostrocaudal axis of PAG. The terminal labeling in PAG from the medial preoptic area was not uniformly distributed throughout PAG, however. Instead, this projection formed one or two rostrocaudally oriented longitudinal columns that terminated in different subregions of PAG along the entire rostrocaudal axis of this structure. Rostrally, inputs from the medial preoptic area project heavily to dorsomedial PAG, and at mid-PAG levels, the projection becomes distinctly bipartite with two discrete longitudinal terminal columns in dorsomedial and lateral PAG; caudally, the heaviest labeling is in ventrolateral PAG. The projection also exhibited a central to peripheral (radial) gradient; labelled fibers and terminals were heaviest near the aqueduct and much lower in the peripheral parts of PAG. WGA-HRP injections in MPO also produced retrograde labeling of neurons at all rostrocaudal levels of PAG; more neurons were labeled in the rostral than the caudal half of PAG. The majority of labeled cells were located in dorsomedial and ventral/ventrolateral parts of PAG; only a few neurons in the dorsal raphe region appear to project to MPO.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reciprocal connections between medial prefrontal cortex and lateral posterior nucleus in rats

The connections of the posterior part of the medial prefrontal cortex with the thalamic lateral posterior nucleus in rats were studied using anterograde and retrograde axonal transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and tritiated leucine. After injections of WGA-HRP into the medial prefrontal cortex, an area confirmed to receive direct projections from the visual cortex, retrogradely labeled neurons were observed ipsilaterally in the lateral posterior nucleus of the thalamus, as well as in the mediodorsal, anteromedial, ventromedial, ventrolateral, laterodorsal, centrolateral, paracentral, rhomboid, parafascicular and posterior nuclei. In the lateral posterior nucleus, the labeled cells were located mainly in the lateroventral portion of its anterior half. In contrast, the posterior half of this nucleus was free of label. Axons labeled by the anterograde transport of tritiated leucine were dispersed over the same region which contained retrogradely labeled cells. The functional significance of these connections is discussed with special reference to their possible role in visuomotor integration in rats.     

Reciprocal parabrachial-cortical connections in the rat

The projection from the parabrachial nucleus (PB) to the cerbral cortex in the rat was studied in detail using the autoradiographic method for tracing anterograde axonal transport and the wheat germ agglutinin-horseradish peroxidase (WGA-HRP) method for both anterograde and retrograde tracing. PB innervates layers I, V and VI of a continuous sheet of cortex extending from the posterior insular cortex caudally, through the dorsal agranular and the granular anterior insular cortex and on rostrally into the lateral prefrontal cortex. Within the prefrontal area, PB fibers innervate primarily layer V of the ventrolateral cortex caudally, but more rostrally the innervated region includes progressively more dorsal portions of the prefrontal area, until by the frontal pole the entire lateral half of the hemisphere is innervated. This projection originates for the most part in a cluster of neurons in the caudal ventral part of the medial PB subdivision, although a few neurons in the adjacent parts of the PB, the Kolliker-Fuse nucleus and the subcoeruleus region also participate.After injection of WGA-HRP into the PB region, retrogradely labeled neurons were found in layer V of the same cortical areas which receive PB inputs. The importance of this monosynaptic reciprocal brainstem-cortical projection as a possible anatomical substrate for the regulation of cortical arousal is discussed.     

Thalamostriatal projections from the ventral anterior nucleus in the dog

Thalamostriatal projections from the ventral anterior nucleus (VA) were mapped by using autoradiographic and horseradish peroxidase techniques in the dog. Injections of tritiated leucine and proline into the lateral, central, and medial parts of VA resulted in anterograde label over the dorsolateral, midlateral, and dorsal parts of the head of the caudate nucleus, respectively. The dorsolateral and midlateral parts of the caudate contained the heaviest label. No silver grains were located over the medial or ventral parts of the caudate. Light to moderate label was located over the most dorsal part of the putamen. After injections of lectin-conjugated horseradish peroxidase (WGA-HRP) into the dorsolateral or intermediate areas of the head of the caudate, retrogradely labeled cells were present in the lateral and central parts of VA, respectively. In cases with dorsolateral caudate injections, labeled cells formed a narrow dorsoventrally oriented band located in the lateral part of VA whereas in the case with a larger injection into midcaudate, large numbers of labeled neurons were scattered throughout the central area of VA. Retrogradely labeled cells were also found in the rostral part of the ventral lateral nucleus (VL). Injections of WGA-HRP into the medial part of the caudate resulted in only a few labeled cells located in the dorsomedial part of VA. Combining these data with those from other studies mapping neostriatal afferents from the cerebral cortex in the dog, it is apparent that the midlateral part of the caudate receiving input from VA also receives afferents from cortical area 6. Furthermore, the dorsolateral part of the caudate that receives input from the lateral part of VA also receives afferents from cortical area 4. These results indicate that the dorsal and lateral parts of the canine caudate nucleus may constitute important links in the transmission and integration of information related to complex motor activities.     

Spinal and trigeminal dorsal horn projections to the parabrachial nucleus in the rat

We studied afferents to the parabrachial nucleus (PB) from the spinal cord and the spinal trigeminal nucleus pars caudalis (SNVc) in the rat by using the anterograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Injections of WGA-HRP into medial PB retrogradely labeled neurons in the promontorium and in lamina I of the dorsal rostral SNVc, while injections into lateral PB and the K?lliker-Fuse nucleus retrogradely labeled neurons in these areas as well as in lamina I throughout the caudal SNVc and spinal dorsal horn. Injections of WGA-HRP into the caudal SNVc and dorsal horn of the spinal cord resulted in terminal labeling in the dorsal, central, and external lateral subnuclei of PB and the K?lliker-Fuse nucleus, all of which are known to receive cardiovascular and respiratory afferent information. Injections of WGA-HRP into the promontorium and dorsal rostral SNVc resulted in terminal labeling in the same PB subnuclei, as well as in the medial and the ventral lateral PB subnuclei, which are sites of relay for gustatory information ascending from the medulla to the forebrain. The spinal and trigeminal projection to PB may mediate the convergence of pain, chemosensory, and temperature sensibilities with gustatory and cardiorespiratory systems in PB.     

Sources of presumptive glutamergic/aspartergic afferents to the rat ventral striatopallidal region

The distribution of presumptive glutamergic and/or aspartergic neurons retrogradely labeled following injections of 3H-D-aspartate (3H-D-Asp) into the ventral striatopallidal region was compared with the distribution of neurons labeled by comparable injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). The afferents labeled by 3H-D-Asp were a subset of those labeled by WGA-HRP. The major sources of afferents to the nucleus accumbens and olfactory tubercle that could be labeled by 3H-D-Asp were in the medial frontal and insular cortices; the olfactory cortex; the lateral, basolateral, and basomedial amygdaloid nuclei; and the midline nuclear complex of the thalamus. The corresponding afferents to the ventral pallidum arose in the central, medial, and basomedial amygdaloid nuclei and the midline thalamic nuclei. In addition, the nucleus of the lateral olfactory tract was moderately or heavily labeled by 3H-D-Asp injections into all three areas, and cells were labeled in the subiculum following injection in the anteromedial part of the nucleus accumbens. Conversely the ventral striatopallidal structures themselves were, at best, sparsely labeled by any of the 3H-D-Asp injections. Neurons in the substantia nigra, ventral tegmental area, dorsal raphe, and locus coeruleus were labeled by WGA-HRP but not by 3H-D-Asp, except for an occasional cell in the raphe. The results indicate that 3H-D-Asp is a specific retrograde tracer and suggest that there are widespread, presumably excitatory, glutamergic and/or aspartergic inputs to the ventral striatum and pallidum.     

Basal forebrain cholinergic and noncholinergic projections to the thalamus and brainstem in cats and monkeys

The projections of basal forebrain neurons to the thalamus and the brainstem were investigated in cats and primates by using retrograde transport techniques and choline acetyltransferase (ChAT) immunohistochemistry. In a first series of experiments, the lectin wheat germ-agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into all major sensory, motor, intralaminar, and reticular (RE) thalamic nuclei of cats and into the mediodorsal (MD) and pulvinar-lateroposterior thalamic nuclei of macaque monkeys. In cats numerous neurons of the vertical and horizontal limbs of the diagonal band nucleus and the substantia innominata (SI), including its rostromedial portion termed the ventral pallidum (VP), were retrogradely labeled after WGA-HRP injections in the rostral pole of the RE complex, the MD, and anteroventral/anteromedial (AV/AM) thalamic nuclei. Fewer retrogradely labeled cells were observed in the same areas after injections in the ventromedial (VM) thalamic nucleus, and none or very few after other thalamic injections. After RE, MD, and AV/AM injections, 7-20% of all retrogradely labeled cells in the basal forebrain were also ChAT positive, while none of the retrogradely labeled neurons following VM injections displayed ChAT immunoreactivity. The basal forebrain projection to the MD nucleus was shown to arise principally from VP in both cats and macaque monkeys. In a second series of experiments performed in cats, injections of WGA-HRP in the brainstem peribrachial (PB) area comprising the pedunculopontine nucleus led to retrograde labeling of a moderate number of neurons in the lateral part of the VP, SI, and preoptic area (POA), only a few of which displayed ChAT immunoreactivity. In addition, a large number of retrogradely labeled cells were observed in the bed nuclei of the anterior commissure and stria terminalis after PB injections. In a third series of experiments, the use of the retrograde double-labeling method with fluorescent tracers in squirrel monkeys allowed us to identify a significant number of basal forebrain neurons sending axon collaterals to both the RE thalamic nucleus and PB brainstem area, while no double-labeled neurons were disclosed after injections confined to the ventral anterior/ventral lateral (VA/VL) thalamic nuclei and PB area or following injections in the cerebral cortex and PB area. Our findings reveal the existence of cholinergic and noncholinergic basal forebrain projections to the thalamus and the brainstem in both cats and macaque monkeys. We suggest that these projections may play a crucial role in the control of thalamic functions in mammals.     

Projections from the lateral geniculate nucleus to the hypothalamus of the Mongolian gerbil (Meriones unguiculatus): an anterograde and retrograde tracing study.

The lateral geniculate nucleus of the thalamus sends efferents to the hypothalamic suprachiasmatic nucleus, which is involved in generation and entrainment of several circadian rhythms. It seems reasonable to believe that the lateral geniculate conveys visual information about the length of the photoperiod to the circadian oscillator. In order to study in more detail the topographical relationship between the lateral geniculate and the suprachiasmatic nucleus, anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheatgerm agglutinin coupled to horseradish peroxidase (WGA-HRP) were performed in the gerbil. After iontophoretic injections of PHA-L in the lateral geniculate, a large number of PHA-L-immunoreactive fibers and nerve terminals were observed in the ventrolateral part of the suprachiasmatic nucleus. Nerve fibers were also present in the ventromedial and dorsolateral portions, particularly in the caudal half of the nucleus. PHA-L-immunoreactive nerve fibers continued outside the borders of the suprachiasmatic nucleus to the adjacent anterior hypothalamic, the periventricular, and the subparaventricular areas. A moderate number of fibers entered the lateral hypothalamic area and the tuber cinerum via the optic tract and chiasm. Moreover, the paraventricular nucleus, the supraoptic nucleus, the medial preoptic area, the lateral preoptic area, and the supramammillary nucleus contained a few labeled fibers. In all parts of the hypothalamus receiving an input from the lateral geniculate, fine beaded immunoreactive fibers with varicosities and nerve terminals were observed, some of which were found in close apposition to hypothalamic neurons. Only after labeling of neurons in the intergeniculate leaflet of the lateral geniculate nucleus, fibers were found in the hypothalamus. This topographical organization of the geniculohypothalamic pathway was supported by retrograde tracing after injections of WGA-HRP in the suprachiasmatic area. In these experiments, retrograde labeled neurons were observed in the intergeniculate leaflet and, in agreement with the anterograde studies, most of labeling was observed in the ipsilateral side. These results confirm that the suprachiasmatic nucleus receives a substantial input from the intergeniculate leaflet of the lateral geniculate. Moreover, the present data demonstrate that the suprachiasmatic nucleus is not the only nucleus that receives a direct visual input. Thus other hypothalamic areas might be influenced by a direct rhythmic neuronal input as well.     

Afferent projections to the interpeduncular nucleus in the rat, as studied by retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase

We examined the afferent projections to the subnuclei of the interpeduncular nucleus (IPN) in the rat by means of retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). We observed locations of retrogradely labeled cells following injections of WGA-HRP into the IPN, and distributions of anterogradely labeled fibers and terminals within the IPN following injections into the areas that contain cells of origin of afferents. Results of the retrograde and anterograde experiments have clarified the detailed organization of the IPN afferents. A part of the nucleus incertus, located dorsomedial to the dorsal tegmental nucleus, projects to the contralateral half of the rostral subnucleus of the IPN; the pars caudalis of the dorsal tegmental nucleus projects sparsely to the rostral lateral, dorsal lateral, lateral, caudal, and apical subnuclei predominantly contralaterally; the laterodorsal tegmental nucleus, to most of the subnuclei predominantly contralaterally; the ventromedial central gray rostral to the dorsal tegmental nucleus and lateral to the dorsal raphe nucleus projects to the rostral lateral and dorsal lateral subnuclei predominantly contralaterally; the median raphe nucleus, substantially to all subnuclei; the medial habenular nucleus, in a topographic manner, to the rostral, central, and intermediate subnuclei, to the rostral lateral and lateral subnuclei predominantly ipsilaterally, and to the dorsal lateral subnucleus predominantly contralaterally; the supramammillary nucleus and areas around the origin of the mammillothalamic tract and near the third ventricle project sparsely to the ventral part of the rostral subnucleus and to the central, lateral, caudal and apical subnuclei; the nucleus of the diagonal band, sparsely to the rostral, central, dorsal lateral, caudal, and apical subnuclei. These differential projections of the afferents to the subnuclei of the IPN may reflect its complex functions within the limbic midbrain circuit.     

Efferent connections of the caudal part of the globus pallidus in the rat

The efferent connections of the caudal pole of the globus pallidus (GP) were examined in the rat by employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L), and the retrograde transport of fluorescent tracers combined with choline acetyltransferase (ChAT) or parvalbumin (PV) immunofluorescence histochemistry. Labeled fibers from the caudal GP distribute to the caudate-putamen, nucleus of the ansa lenticularis, reuniens, reticular thalamic nucleus (mainly its posterior extent), and along a thin strip of the zona incerta adjacent to the cerebral peduncle. The entopeduncular and subthalamic nuclei do not appear to receive input from the caudal GP. Descending fibers from the caudal GP course in the cerebral peduncle and project to posterior thalamic nuclei (the subparafascicular and suprageniculate nuclei, medial division of the medial geniculate nucleus, and posterior intralaminar nucleus/peripeduncular area) and to extensive brainstem territories, including the pars lateralis of the substantia nigra, lateral terminal nucleus of the accessory optic system, nucleus of the brachium of the inferior colliculus, nucleus sagulum, external cortical nucleus of the inferior colliculus, cuneiform nucleus, and periaqueductal gray. In cases with deposits of PHA-L in the ventral part of the caudal GP, labeled fibers in addition distribute to the lateral amygdaloid nucleus, amygdalostriatal transition area, cerebral cortex (mainly perirhinal, temporal, and somatosensory areas) and rostroventral part of the lateral hypothalamus. Following injections of fluorescent tracer centered in the lateral hypothalamus, posterior intralaminar nucleus, substantia nigra, pars lateralis, or lateral terminal nucleus, a substantial number of retrogradely labeled cells is observed in the caudal GP. None of these cells express ChAT immunoreactivity, but, except for the ones projecting to the lateral hypothalamus, a significant proportion is immunoreactive to PV. Our results indicate that caudal GP efferents differ from those of the rostral GP in that they project to extensive brainstem territories and appear to be less intimately related to intrinsic basal ganglia circuits. Moreover, our data suggest a possible participation of the caudal GP in feedback loops involving posterior cortical areas, posterior striatopallidal districts, and posterior thalamic nuclei. Taken as a whole, the projections of the caudal GP suggest a potential role of this pallidal district in visuomotor and auditory processes. © 1996 Wiley-Liss, Inc.