Thalamo-insular pathway conveying orofacial muscle proprioception in the rat.

Little is known about how proprioceptive signals arising from muscles reach to higher brain regions such as the cerebral cortex. We have recently shown that a particular thalamic region, the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM), receives the proprioceptive signals from jaw-closing muscle spindles (JCMSs) in rats. In this study, we further addressed how the orofacial thalamic inputs from the JCMSs were transmitted from the thalamus (VPMcvm) to the cerebral cortex in rats. Injections of a retrograde and anterograde neuronal tracer, wheat-germ agglutinin-conjugated horseradish peroxidase (WGA-HRP), into the VPMcvm demonstrated that the thalamic pathway terminated mainly in a rostrocaudally narrow area in the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of the secondary somatosensory cortex (dGIrvs2). We also electrophysiologically confirmed that the dGIrvs2 received the proprioceptive inputs from JCMSs. To support the anatomical evidence of the VPMcvm-dGIrvs2 pathway, injections of a retrograde neuronal tracer Fluorogold into the dGIrvs2 demonstrated that the thalamic neurons projecting to the dGIrvs2 were confined in the VPMcvm and the parvicellular part of ventral posterior nucleus. In contrast, WGA-HRP injections into the lingual nerve area of core VPM demonstrated that axon terminals were mainly labeled in the core regions of the primary and secondary somatosensory cortices, which were far from the dGIrvs2. These results suggest that the dGIrvs2 is a specialized cortical region receiving the orofacial proprioceptive inputs. Functional contribution of the revealed JCMSs-VPMcvm-dGIrvs2 pathway to Tourette syndrome is also discussed.

Efferent connections of the parvalbumin-positive (PV1) nucleus in the lateral hypothalamus of rodents.

A solitary cluster of parvalbumin-positive neurons--the PV1 nucleus--has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the PV1 nucleus using nonspecific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1 nucleus was found to project mainly to the periaqueductal grey matter (PAG), predominantly ipsilaterally. Indirectly in rats and directly in mice, a discrete, longitudinally oriented cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF is particularly dense in the rostral portion, which is located in the supraoculomotor nucleus (Su3). It is spatially interrupted over a short stretch at the level of the trochlear nucleus and abuts caudally on a second parvalbumin-positive (PV2) nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings, which stem from neurons scattered throughout the PV1 nucleus. Topographically, the longitudinal orientation of the PV1-CTF accords with that of the likewise longitudinally oriented functional modules of the PAG, but overlaps none of them. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger-Westphal, the lateral habenular, and the laterodorsal tegmental nuclei. So far, no obvious functions have been attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1 nucleus.

Tracing thalamo-cortical connections in tenrecA further attempt to characterize poorly differentiated neocortical regions, particularly the motor cortex.

The hedgehog tenrec (Afrosoricidae) has a very poorly differentiated neocortex. Previously its primary sensory regions have been characterized with hodological and electrophysiological techniques. Unlike the marsupial opossum the tenrec may also have a separate motor area as far as there are cortico-spinal cells located rostral to the primary somatosensory cortex. However, not knowing its thalamic input it may be premature to correlate this area with the true (mirror-image-like) primary motor cortex in higher mammals. For this reason the tenrec's thalamo-cortical connections were studied following tracer injections into various neocortical regions. The main sensory areas were confirmed by their afferents from the principal thalamic nuclei. The dorsal lateral geniculate nucleus, in addition, was connected with the retrosplenial area and a rostromedial visual region. Unlike the somatosensory cortex the presumed motor area did not receive afferents from the ventrobasal thalamus but fibers from the cerebello-thalamic target regions. These projections, however, were not restricted to the motor area, but involved the entire somatosensorimotor field as well as adjacent regions. The projections appeared similar to those arising in the rat thalamic ventromedial nucleus known to have a supporting function rather than a specific motor task. The question was raised whether the input from the basal ganglia might play a crucial role in the evolution of the mammalian motor cortex? Certainly, in the tenrec, the poor differentiation of the motor cortex coincides with the virtual absence of an entopeduncular projection to the ventrolateral thalamus.

Branched projections in the auditory thalamocortical and corticocortical systems.

Branched axons (BAs) projecting to different areas of the brain can create multiple feature-specific maps or synchronize processing in remote targets. We examined the organization of BAs in the cat auditory forebrain using two sensitive retrograde tracers. In one set of experiments (n=4), the tracers were injected into different frequency-matched loci in the primary auditory area (AI) and the anterior auditory field (AAF). In the other set (n=4), we injected primary, non-primary, or limbic cortical areas. After mapped injections, percentages of double-labeled cells (PDLs) in the medial geniculate body (MGB) ranged from 1.4% (ventral division) to 2.8% (rostral pole). In both ipsilateral and contralateral areas AI and AAF, the average PDLs were <1%. In the unmapped cases, the MGB PDLs ranged from 0.6% (ventral division) after insular cortex injections to 6.7% (dorsal division) after temporal cortex injections. Cortical PDLs ranged from 0.1% (ipsilateral AI injections) to 3.7% in the second auditory cortical area (AII) (contralateral AII injections). PDLs within the smaller (minority) projection population were significantly higher than those in the overall population. About 2% of auditory forebrain projection cells have BAs and such cells are organized differently than those in the subcortical auditory system, where BAs can be far more numerous. Forebrain branched projections follow different organizational rules than their unbranched counterparts. Finally, the relatively larger proportion of visual and somatic sensory forebrain BAs suggests modality specific rules for BA organization.

Thalamic connections of the dorsal and ventral premotor areas in New World owl monkeys.

Thalamic connections of two premotor cortex areas, dorsal (PMD) and ventral (PMV), were revealed in New World owl monkeys by injections of fluorescent dyes or wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The injections were placed in the forelimb and eye-movement representations of PMD and in the forelimb representation of PMV as determined by microstimulation mapping. For comparison, injections were also placed in the forelimb representation of primary motor cortex (M1) of two owl monkeys. The results indicate that both PMD and PMV receive dense projections from the ventral lateral (VL) and ventral anterior (VA) thalamus, and sparser projections from the ventromedial (VM), mediodorsal (MD) and intralaminar (IL) nuclei. Labeled neurons in VL were concentrated in the anterior (VLa) and the medial (VLx) nuclei, with only a few labeled cells in the dorsal (VLd) and posterior (VLp) nuclei. In VA, labeled neurons were concentrated in the parvocellular division (VApc) dorsomedial to VLa. Labeled neurons in MD were concentrated in the most lateral and posterior parts of the nucleus. VApc projected more densely to PMD than PMV, especially to rostral PMD, whereas caudal PMD received stronger projections from neurons in VLx and VLa. VLd projected exclusively to PMD, and not to PMV. In addition, neurons labeled by PMD injections tended to be more dorsal in VL, IL, and MD than those labeled by PMV injections. The results indicate that both premotor areas receive indirect inputs from the cerebellum (via VLx, VLd and IL) and globus pallidus (via VLa, VApc, and MD). Comparisons of thalamic projections to premotor and M1 indicate that both regions receive strong projections from VLx and VLa, with the populations of cells projecting to M1 located more laterally in these nuclei. VApc, VLd, and MD project mainly to premotor areas, while VLp projects mainly to M1. Overall, the thalamic connectivity patterns of premotor cortex in New World owl monkeys are similar to those reported for Old World monkeys.

Thalamocortical and the dual pattern of corticothalamic projections of the posterior parietal cortex in macaque monkeys.

The corticothalamic projection includes a main, modulatory projection from cortical layer VI terminating with small endings whereas a less numerous, driving projection from layer V forms giant endings. Such dual pattern of corticothalamic projections is well established in rodents and cats for many cortical areas. In non-human primates (monkeys), it has been reported for the primary sensory cortices (A1, V1, S1), the motor and premotor cortical areas and, in the parietal lobe, also for area 7. The present study aimed first at refining the cytoarchitecture parcellation of area 5 into the sub-areas PE and PEa and, second, establishing whether area 5 also exhibits this dual pattern of corticothalamic projection and what is its precise topography. To this aim, the tracer biotinylated dextran amine (BDA) was injected in area PE in one monkey and in area PEa in a second monkey. Area PE sends a major projection terminating with small endings to the thalamic lateral posterior nucleus (LP), ventral posterior lateral nucleus (VPL), medial pulvinar (PuM) and, but fewer, to ventral lateral posterior nucleus, dorsal division (VLpd), central lateral nucleus (CL) and center median nucleus (CM), whereas giant endings formed restricted terminal fields in LP, VPL and PuM. For area PEa, the corticothalamic projection formed by small endings was found mainly in LP, VPL, anterior pulvinar (PuA), lateral pulvinar (PuL), PuM and, to a lesser extent, in ventral posterior inferior nucleus (VPI), CL, mediodorsal nucleus (MD) and CM. Giant endings originating from area PEa formed restricted terminal fields in LP, VPL, PuA, PuM, MD and PuL. Furthermore, the origin of the thalamocortical projections to areas PE and PEa was established, exhibiting clusters of neurons in the same thalamic nuclei as above, in other words predominantly in the caudal thalamus. Via the giant endings CT projection, areas PE and PEa may send feedforward, transthalamic projections to remote cortical areas in the parietal, temporal and frontal lobes contributing to polysensory and sensorimotor integration, relevant for visual guidance of reaching movements for instance.

The spinal cord connections of the myofascial trigger spots.

BACKGROUND: Recent electrophysiological studies revealed that endplate noise (EPN) could be specifically recorded from a myofascial trigger point (MTrP) region. EPN has been considered as the focal graded potentials due to excessive acetylcholine release in neuromuscular junction. A recent histological study has demonstrated a free nerve ending at the vicinity of the site, from where EPN could be recorded in an MTrP region. However, the sensory (afferent) and the motor (efferent) connections between an MTrP and the spinal cord still has never been fully studied. AIMS: The aim of this study was to delineate both motor and sensory connections between an MTrP and the spinal cord by applying the stain with horseradish peroxidase (HRP). METHODS: Nine Wistar rats were studied. When the rat was anesthetized, its biceps femoris muscles were exposed for localizing the myofascial trigger spot (MTrS, equivalent to MTrP in human). In one side, a monopolar Teflon-coated, hollow-needle electrode was used for searching EPN in an MTrS region, and then HRP was injected via this hollow-needle electrode into the site where EPN was recorded. HRP was also injected into a normal (non-taut band, non-MTrS) site in the contralateral side to obtain the control data. Two days after HRP injection, the rats were sacrificed and their spinal cords and dorsal root ganglia (DRG) were sectioned for the identification of the sites where neurons were labeled with HRP. RESULTS: The HRP-labeled neurons were found in the ventral horn of the spinal cord and in the DRG over L3, L4, and L5, while most were found in the L5 level. The mean numbers of HRP-labeled neurons in the EPN side looked smaller than that in the control side, but the difference did not reach statistically significant level (P>0.05). The mean values of the diameters of the HRP-labeled neurons in the DRG were not significantly different between the EPN side and the control side (P>0.05). However, HRP-neurons in the ventral horn of the spinal cord in the EPN side showed mild tendency to be smaller than that in the control side. CONCLUSIONS: The spinal cord connections of an MTrS are basically similar to that for a normal tissue region. The motor neurons related to MTrS tended to be smaller in their diameters. The findings in this study further supported the previously proposed hypotheses for the pathogenesis of an MTrP.

Projections of somatosensory cortex and frontal eye fields onto incertotectal neurons in the cat.

The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection.

Crossmodal audio-visual interactions in the primary visual cortex of the visually deprived cat: a physiological and anatomical study.

Blind individuals often demonstrate enhanced non-visual perceptual abilities. Neuroimaging and transcranial magnetic stimulation experiments have suggested that computations carried out in the occipital cortex may underlie these enhanced somatosensory or auditory performances. Thus, cortical areas that are dedicated to the analysis of the visual scene may, in the blind, acquire the capacity to participate in other sensory processing. However, the neural substrate that underlies this transfer of function is not fully characterized. Here we studied the synaptic and anatomical basis of this phenomenon in cats that were visually deprived by dark rearing, either early visually deprived after birth (EVD), or late visually deprived after the end of the critical period (LVD); data were compared with those obtained in normally reared cats (controls). The presence of synaptic and spike responses to auditory stimulation was examined by means of intracellular recordings in area 17 and the border between areas 17 and 18. While none of the cells recorded in control and LVD cats showed responses to sound, 14% of the cells recorded in EVD cats showed both subthreshold synaptic responses and suprathreshold spike responses to auditory stimuli. Synaptic responses were of small amplitude, but well time-locked to the stimuli and had an average latency of 30+/-12ms. In an attempt to identify the origin of the inputs carrying auditory information to the visual cortex, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected in the visual cortex and retrograde labeling examined in the cortex and thalamus. No significant retrograde labeling was found in auditory cortical areas. However, the proportion of neurons projecting from supragranular layers of the posteromedial and posterolateral parts of the lateral suprasylvian region to V1 was higher than that in control cats. Retrograde labeling in the lateral geniculate nucleus showed no difference in the total number of neurons between control and visually deprived cats, but there was a higher proportion of labeling in C-laminae in deprived cats. Labeled cells were not found in the medial geniculate nucleus, a thalamic relay for auditory information, in either control or visually deprived cats. Finally, immunohistochemistry of the visual cortex of deprived cats revealed a striking decrease in pavalbumin- and calretinin-positive neurons, the functional implications of which we discuss.

Thalamo-striatal projections in the hedgehog tenrec.

Unlike the basal ganglia input from the midline and intralaminar nuclei, the origin and prominence of striatal projections arising in the lateral thalamus varies considerably among mammals being most restricted in the opossum and monkey, most extensive in the rat. To get further insight into the evolution of thalamo-striatal pathways the Madagascar lesser hedgehog tenrec (Afrotheria) was investigated using anterograde and retrograde flow techniques. An extensive medial thalamic region (including presumed equivalents to the paraventricular, parataenial and dorsomedial nuclei as well as the reuniens complex), the rostral (central) and caudal (parafascicular) intralaminar nuclei were shown to give rise to striatal projections. Additional projections originated in the ventral anterolateral nuclear group and regions within and around the medial geniculate complex. Similar to the rat there was also substantial projections from the lateral posterior-pulvinar complex and the ventral posterior nucleus. The fibers terminated extensively across the striatum in a mainly homogeneous fashion. Isolated patches of low-density terminations were found in the caudoputamen. This inhomogeneous labeling pattern appeared similar to one described in the cat with the unlabeled islands showing features of striosomes. The medial and intralaminar nuclei also projected heavily upon the olfactory tubercle. Differential innervation patterns were noted in the polymorphous layer, the deep and the superficial molecular layer.

Cortical, callosal, and thalamic connections from primary somatosensory cortex in the naked mole-rat (Heterocephalus glaber), with special emphasis on the connectivity of the incisor representation.

We investigated the distribution of cortical, callosal, and thalamic connections from the primary somatosensory area (S1) in naked mole-rats, concentrating on lower incisor and forelimb representations. A neuronal tracer (WGA-HRP) was injected into the center of each respective representation under guidance from microelectrode recordings of neuronal activity. The locations of cells and terminals were determined by aligning plots of labeled cells with flattened cortical sections reacted for cytochrome oxidase. The S1 lower incisor area was found to have locally confined intrahemispheric connections and longer connections to a small cluster of cells in the presumptive secondary somatosensory (S2) and parietal ventral (PV) incisor fields. The S1 incisor area also had sparse connections with anterior cortex, in presumptive primary motor cortex. Homotopic callosal projections were identified between the S1 lower incisor areas in each hemisphere. Thalamocortical connections related to the incisor were confined to ventromedial portions of the ventral posterior medial subnucleus (VPM) and posterior medial nucleus (Po). Injections into the S1 forelimb area revealed reciprocal intrahemispheric connections to S2 and PV, to two areas in frontal cortex, and to two areas posterior to S1 that appear homologous to posterior lateral area and posterior medial area in rats. The S1 forelimb representation also had callosal projections to the contralateral S1 limb area and to contralateral S2 and PV. Thalamic distribution of label from forelimb injections included ventral portions of the ventral posterior lateral subnucleus (VPL), dorsolateral Po, the ventral lateral nucleus, and the ventral medial nucleus and neighboring intralaminar nuclei.

Extension of corticocortical afferents into the anterior bank of the intraparietal sulcus by tool-use training in adult monkeys.

When humans use a tool, it becomes an extension of the hand physically and perceptually. Common introspection might occur in monkeys trained in tool-use, which should depend on brain operations that constantly update and automatically integrate information about the current intrinsic (somatosensory) and the extrinsic (visual) status of the body parts and the tools. The parietal cortex plays an important role in using tools. Intraparietal neurones of naïve monkeys mostly respond unimodally to somatosensory stimuli; however, after training these neurones become bimodally active and respond to visual stimuli. The response properties of these neurones change to code the body images modified by assimilation of the tool to the hand holding it. In this study, we compared the projection patterns between visually related areas and the intraparietal cortex in trained and naïve monkeys using tracer techniques. Light microscopy analyses revealed the emergence of novel projections from the higher visual centres in the vicinity of the temporo-parietal junction and the ventrolateral prefrontal areas to the intraparietal area in monkeys trained in tool-use, but not in naïve monkeys. Functionally active synapses of intracortical afferents arising from higher visual centres to the intraparietal cortex of the trained monkeys were confirmed by electron microscopy. These results provide the first concrete evidence for the induction of novel neural connections in the adult monkey cerebral cortex, which accompanies a process of demanding behaviour in these animals.

The organization of the brainstem and spinal cord of the mouse: relationships between monoaminergic, cholinergic, and spinal projection systems.

Information regarding the organization of the CNS in terms of neurotransmitter systems and spinal connections in the mouse is sparse, especially at the level of the brainstem. An overview is presented of monoaminergic and cholinergic systems in the brainstem and spinal cord that were visualized immunohistochemically in inbred C57BL/6 and outbred CD-1 mice. This information is complemented with data on spinal cord-projecting systems that were characterized using retrograde tracing, spinal hemisections, and double labeling techniques. Attention is given to differences in these systems related to spinal levels. The data are discussed with reference to studies in the rat, and to standardized information as provided in the atlas of the mouse brain. Although the overall organization of these systems in the mouse is largely similar to those in the rat, species differences are present in relative location, size and/or connectivity of cell groups. For example, catecholaminergic neurons in the (ventro)lateral pons (A5 and A7 cell groups) in the mouse project to the spinal cord mainly via contralateral, and not ipsilateral, pathways. The data further supplement information as provided in standardized brainstem sections of the C57BL/6 mouse [Paxinos, G., Franklin, K.B.J., 2001. The mouse brain in stereotaxic coordinates. Academic Press, San Diego], especially with respect to the size and/or location of the catecholaminergic retrorubral field (A8 group), A5, A1, and C1 cell groups, and the serotonergic B4 group, reticulotegmental nucleus (B9 group), lateral paragigantocellular nucleus and raphe magnus nucleus (B3 group). Altogether this study provides a comprehensive overview of the spatial relationships of neurochemically and anatomically defined neuronal systems in the mouse brainstem and spinal cord.

Striatal projections from the lateral and posterior thalamic complexes. An anterograde tracer study in the cat.

Striatal projections from the lateral intermediate (LI) and posterior (Po) thalamic complexes were studied with the anterograde tracers wheat germ agglutinin-horseradish peroxidase and Phaseolus vulgaris leucoagglutinin. Projections to the lateral part of the head and body of the caudate nucleus (CN) and to the putamen (Pu) were found to arise from the ventral parts of the caudal subdivision of the LI besides the well established sources in the intralaminar and ventral thalamic nuclei. No projections to the CN and only a few to the Pu were found to arise from the medial division of the Po. The presence of terminal and intercalated varicosities in the thalamostriatal fibers suggests that they form both terminal and en passant synapses. Thalamostriatal fibers from these thalamic sectors were unevenly distributed within the CN, with patches of either low-density innervation or with no projections at all interspersed within irregular, more densely innervated areas. The former coincided with the acetylcholinesterase-poor striosomes and the latter areas of dense projection with the extrastriosomal matrix.

Dual axonal terminations from the retrosplenial and visual association cortices in the laterodorsal thalamic nucleus of the rat.

Light and electron microscopic tracing studies were conducted to assess the synaptic organization in the laterodorsal thalamic nucleus (LD) of the rat and the laminar origins of corticothalamic terminals from the retrosplenial and visual association cortices to LD. A survey of the general ultrastructure of LD revealed at least three types of presynaptic terminals identified on the basis of size, synaptic vesicle morphology, and synaptic membrane specializations: (1) small axon terminals with round synaptic vesicles (SR), which accounted for the majority of terminal profiles and made asymmetric synaptic contacts predominantly with small dendritic shafts and spines; (2) large axon terminals with round synaptic vesicles (LR), which formed asymmetric synaptic contacts mainly with large dendritic shafts; and (3) small to medium-size axon terminals with pleomorphic synaptic vesicles (SMP), which symmetrically synapsed with a wide range of postsynaptic structures from cell bodies to small dendrites. Synaptic glomeruli were identified, whereas no presynaptic dendrites were found. To characterize and identify corticothalamic terminals arising from the retrosplenial and visual association cortices that project to LD, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was injected into these cortices. Axons anterogradely labeled with WGA-HRP ended in both SR and LR terminals. On the other hand, dextran-tetramethylrhodamine injected into LD as a retrograde fluorescent tracer labeled large pyramidal cells of layer V as well as small round or multiform cells of layer VI in the retrosplenial and visual association cortices. These findings provide the possibility that corticothalamic terminations from cortical neurons in layer V end as LR terminals, while those from neurons in layer VI end as SR boutons.

Retrograde study of hypocretin-1 (orexin-A) projections to subdivisions of the dorsal raphe nucleus in the rat.

A retrograde tracer, WGA-apo-HRP-gold (WG), was injected into each subdivision of the dorsal raphe (DR) nucleus, and subsequent orexin-A immunostaining was performed for the tuberal region of the hypothalamus in order to investigate orexin projections to the DR. Similar to previous studies, the majority of orexin-single-labeled neurons were observed at the dorsal half of the lateral hypothalamus (LH), the circle around the fornix, i.e., perifornical nucleus (PeF), and the area dorsal to the fornix. The present study reports that hypothalamic neurons exhibited differential projections to each subdivision of the DR. Following WG injections into rostral DR, WG-single-labeled cells were observed at the dorsal half of the LH as well as dorsomedial hypothalamic nucleus. The major input to the intermediate DR originates from the ventromedial portion of the LH, PeF, and the area dorsal to the PeF, whereas one to lateral wing DR derived from PeF as well as the ventrolateral portion of the LH. Following WG injections into caudal DR, WG-single-labeled cells were located at ventromedial LH and the ventrolateral portion of the posterior hypothalamus. Following WG injections into each DR subdivision, WG/orexin-double-labeled neurons were observed at LH, PeF, and the area dorsal to the PeF. Only a few double-labeled cells were observed in dorsomedial and posterior hypothalamic nuclei. Our observations suggest that various hypothalamic neurons differentially project to each subdivision of the DR, a portion of which is orexin-immunoreactive. These orexin-immunoreactive DR-projecting hypothalamic neurons might have wake-related influences over a variety of brain functions subject to DR efferent regulation, including affective behavior, autonomic control, nociception, cognition, and sensorimotor integration.

In cat four times as many lamina I neurons project to the parabrachial nuclei and twice as many to the periaqueductal gray as to the thalamus.

The spinothalamic tract, and especially its fibers originating in lamina I, is the best known pathway for transmission of nociceptive information. On the other hand, different studies have suggested that more lamina I cells project to the parabrachial nuclei (PBN) and periaqueductal gray (PAG) than to the thalamus. The exact ratio of the number of lamina I projections to PBN, PAG and thalamus is not known, because comprehensive studies examining these three projections from all spinal segments, using the same tracers and counting methods, do not exist. In the present study, the differences in number and distribution of retrogradely labeled lamina I cells in each segment of the cat spinal cord (C1-Coc2) were determined after large wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injections in either PBN, PAG or thalamus. We estimate that approximately 6000 lamina I cells project to PBN, 3000 to PAG and less than 1500 to the thalamus. Of the lamina I cells projecting to thalamus or PAG more than 80%, and of the lamina I-PBN cells approximately 60%, were located on the contralateral side. In all cases, most labeled lamina I cells were found in the upper two cervical segments and in the cervical and lumbar enlargements.

C1-C3 spinal cord projections to periaqueductal gray and thalamus: a quantitative retrograde tracing study in cat.

By far, the strongest spinal cord projections to periaqueductal gray (PAG) and thalamus originate from the upper three cervical segments, but their precise organization and function are not known. In the present study in cat, tracer injections in PAG or in thalamus resulted in more than 2400 labeled cells, mainly contralaterally, in the first three cervical segments (C1-C3), in a 1:4 series of sections, excluding cells in the dorsal column and lateral cervical nuclei. These cells represent about 30% of all neurons in the entire spinal cord projecting to PAG and about 45% of all spinothalamic neurons. About half of the C1-C3 PAG and C1-C3 thalamic neurons were clustered laterally in the ventral horn (C(1-3vl)), bilaterally, with a slight ipsilateral preponderance. The highest numbers of C(1-3vl)-PAG and C(1-3vl)-thalamic cells were found in C1, with the greatest density rostrocaudally in the middle part of C1. A concept is put forward that C(1-3vl) cells relay information from all levels of the cord to PAG and/or thalamus, although the processing of specific information from upper neck muscles and tendons or facet joints might also play a role.

Neurochemical characterization of the cerebellar-recipient motor thalamic territory in the macaque monkey.

Abstract The immunoarchitectonics of the macaque motor thalamus was analysed to look for a possible neurochemical characterization of thalamic territories, which were not definable cytoarchitectonically, associated with different functional pathways. Thalamic sections from 15 macaque monkeys were processed for visualization of calbindin (CB), parvalbumin (PV), calretinin (CR) and SMI-32 immunoreactivity (ir). PV-, CR- and SMI-32ir distributions did not show any clear correlation with known functional subdivisions. In contrast, CBir distribution reliably defined two markedly distinct motor thalamic territories, one characterized by high cell and neuropil CBir (CB-positive territory), the other by very low cell and neuropil CBir (CB-negative territory). These two neurochemically distinct compartments, the CB-negative and the CB-positive territories, appear to correspond to the cerebellar- and basal ganglia-recipient territories, respectively. To verify the possible correspondence of the CB-negative territory with the cerebellar-recipient sector of the motor thalamus, we compared the distribution of cerebello-thalamic projections with the distribution of CBir in two monkeys. The distribution of cerebellar afferent terminals was similar to that reported from previous reports and in line with the notion that in the motor thalamus the cerebellar-recipient territory does not respect cytoarchitectonic boundaries. Comparison with CB immunoarchitecture showed very close correspondence in the motor thalamus between the distribution of the anterograde labeling and the CB-negative territory, suggesting that the CB-negative territory represents the architectonic counterpart of the cerebellar-recipient territory. CB immunostaining may therefore represent a helpful tool for describing the association between thalamocortical projections and the basal ganglia or the cerebellar loops and for establishing possible homologies between the motor thalamus of non-human primates and humans.

Neurons in the lateral sacral cord of the cat project to periaqueductal grey, but not to thalamus.

Previous work of our laboratory has shown that neurons in the lateral sacral cord in cat project heavily to the periaqueductal grey (PAG), in all likelihood conveying information from bladder and genital organs. In humans this information usually does not reach consciousness, which raises the question of whether the lateral sacral cell group projects to the thalamus. After wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) injections into the sacral cord, anterogradely labelled fibers were found in the thalamus, specifically in the ventral anterior and ventral lateral nuclei, the medial and intralaminar nuclei, the lateral ventrobasal complex/ventroposterior lateral nucleus, and the nucleus centre median, lateral to the fasciculus retroflexus. Much denser projections were found to the central parts of the PAG, mainly to its dorsolateral and ventrolateral parts at caudal levels and lateral parts at intermediate levels. In a subsequent retrograde tracing study, injections were made in those parts of the thalamus that received sacral fibers, as found in the anterograde study. Labelled neurons were observed in the sacral cord, but not in the lateral sacral cell group. In contrast, a small control injection in the caudal PAG resulted in many labelled neurons in the lateral sacral cord. These results suggest that afferent information regarding micturition and sexual behaviour is relayed to the PAG, rather than to the thalamus.