Diencephalic projections from the superficial and deep laminae of the medullary dorsal horn in the rat.

An important function of the medullary dorsal horn (MDH) is the relay of nociceptive information from the face and mouth to higher centers of the central nervous system. We studied the central projection pattern of axons arising from the MDH by examining the axonal transport of Phaseolus vulgaris-leucoagglutinin (PHA-L). Labeled axon and axon terminal distributions arising from the MDH were analyzed at the light microscopic level. After large injections of PHA-L into both superficial and deep laminae of the MDH in the rat, labeled axons were observed in the nucleus submedius of the thalamus (SUB), ventroposterior thalamic nucleus medialis (VPM), ventroposterior thalamic nucleus parvicellularis (VPPC), posterior thalamic nuclei (PO), zona incerta (ZI), lateral hypothalamic nucleus (LH), and posterior hypothalamic nucleus (PH). Restriction of PHA-L into only the superficial laminae resulted in heavy axon and varicosity labeling in the SUB, VPM, PO, and VPPC and light labeling in LH. In contrast, after injections into deep laminae, labeled axons were mainly distributed in ZI and PH; some were also in VPM and LH, and fewer still in PO and SUB. Varicosities in VPM, SUB, and PO were significantly larger than those in VPPC, ZI, LH, and PH. Varicosity density was highest in SUB and lowest in the VPPC. We concluded that there are two distinct nociceptive pathways, one originating from the superficial MDH and terminating primarily in the dorsal diencephalon and the second originating from deep laminae of the MDH and terminating primarily in the ventral diencephalon. We propose that in the rat, input from the deeper laminae is primarily involved in the motivational-affective component of pain, whereas input from the superficial MDH is related to both the sensory-discriminative and motivational-affective component of pain.     

Both oral and caudal parts of the spinal trigeminal nucleus project to the somatosensory thalamus in the rat

Recent evidence has been accumulated that not only spinal trigeminal nucleus caudalis (Sp5C) neurons but also spinal trigeminal nucleus oralis (Sp5O) neurons respond to noxious stimuli. It is unknown, however, whether Sp5O neurons project to supratrigeminal structures implicated in the sensory processing of orofacial nociceptive information. This study used retrograde tracing with Fluorogold in rats to investigate and compare the projections from the Sp5O and Sp5C to two major thalamic nuclei that relay ascending somatosensory information to the primary somatic sensory cortex: the ventroposteromedial thalamic nucleus (VPM) and the posterior thalamic nuclear group (Po). Results not only confirmed the existence of contralateral projections from the Sp5C to the VPM and Po, with retrogradely labelled neurons displaying a specific distribution in laminae I, III and V, they also showed consistent and similar numbers of retrogradely labelled cell bodies in the contralateral Sp5O. In addition, a topographic distribution of VPM projections from Sp5C and Sp5O was found: neurons in the dorsomedial parts of Sp5O and Sp5C projected to the medial VPM, neurons in the ventrolateral Sp5O and Sp5C projected to the lateral VPM, and neurons in intermediate parts of Sp5O and Sp5C projected to the intermediate VPM. All together, these data suggest that not only the Sp5C, but also the Sp5O relay somatosensory orofacial information from the brainstem to the thalamus. Furthermore, trigemino-VPM pathways conserve the somatotopic distribution of primary afferents found in each subnucleus. These results thus improve our understanding of trigeminal somatosensory processing and help to direct future electrophysiological investigations.     

Distribution of trigeminothalamic and spinothalamic lamina I terminations in the macaque monkey

Thalamic terminations from trigeminal, cervical, and lumbosacral lamina I neurons were investigated with Phaseolus vulgaris leucoagglutinin (PHA-L) and labeled dextrans. Iontophoretic injections guided by physiological recordings were restricted to lamina I or laminae I-II. PHA-L-labeled trigemino- and spinothalamic (TSTT) terminations were identified immunohistochemically. TRITC- and FITC-labeled dextrans were injected at different levels to confirm topography. Terminations consistently occurred in two main locations: a distinguishable portion of posterolateral thalamus identified cytoarchitectonically as the posterior part of the ventral medial nucleus (VMpo) and a portion of posteromedial thalamus designated as the ventral caudal part of the medial dorsal nucleus (MDvc). In addition, isolated fibers bearing boutons of passage were observed in the ventral posterior medial and lateral (VPM and VPL) nuclei, and spinal terminations occurred in the ventral posterior inferior nucleus (VPI). Isolated terminations occasionally occurred in other sites (e.g., suprageniculate, zona incerta, hypothalamic paraventricular n.). Terminations in MDvc occurred in concise foci that were weakly organized topographically (posteroanterior = rostrocaudal). Terminations in VMpo consisted of dense clusters of ramified terminal arbors bearing multiple large boutons that were well organized topographically (anteroposterior = rostrocaudal). Terminations in VMpo colocalized with a field of calbindin-immunoreactive terminal fibers; double-labeled terminals were documented at high magnification. This propitious marker was especially useful at anterior levels, where VMpo can easily be misidentified as VPM. These findings demonstrate phylogenetically novel primate lamina I TSTT projections important for sensory and motivational aspects of pain, temperature, itch, muscle ache, sensual touch, and other interoceptive feelings from the body.     

Calbindin and parvalbumin cells in monkey VPL thalamic nucleus: distribution, laminar cortical projections, and relations to spinothalamic terminations.

The ventral posterior lateral nucleus (VPL) of the monkey thalamus was investigated by histochemical staining for cytochrome oxidase (CO) activity and by immunocytochemical staining for the calcium-binding proteins parvalbumin and 28 kDa calbindin. Anterograde and retrograde tracing experiments were used to correlate patterns of differential distribution of CO activity and of parvalbumin and calbindin cells with the terminations of spinothalamic tract fibers and with the types of cells projecting differentially to superficial and deeper layers of primary somatosensory cortex (SI). VPL is composed of CO-rich and CO-weak compartments. Cells are generally smaller in the CO-weak compartment. Parvalbumin-immunoreactive cells and parvalbumin-immunoreactive medial lemniscal fiber terminations are confined to the CO-rich compartment. Calbindin-immunoreactive cells are found in both the CO-rich and CO-weak compartments. The CO-weak compartment, containing only calbindin cells, forms isolated zones throughout VPL and expands as a cap covering the posterior surface of the ventral posterior medial nucleus (VPM). Spinothalamic tract terminations tend to be concentrated in the CO-weak compartment, especially in the posterior cap. Other CO-weak, parvalbumin-negative, calbindin-positive nuclei, including the posterior, ventral posterior inferior, and anterior pulvinar and the small-celled matrix of VPM are also associated with concentrations of spinothalamic and caudal trigeminothalamic terminations. Parvalbumin cells are consistently larger than calbindin cells and are retrogradely labeled only after injections of tracers in middle and deep layers of SI. The smaller calbindin cells are the only cells retrogradely labeled after placement of retrograde tracers that primarily involve layer I of SI. The compartmental organization of VPL is similar to but less rigid than that previously reported in VPM. VPL and VPM relay cells projecting to different layers of SI cortex can be distinguished by differential immunoreactivity for the two calcium-binding proteins. The small-celled, CO-weak, calbindin-positive zones of VPL and VPM appear to form part of a wider system of smaller thalamic neurons unconstrained by traditional nuclear boundaries that are preferentially the targets of spinothalamic and caudal trigeminal inputs, and that may have preferential access to layer I of SI.     

Retrograde analyses of spinothalamic projections in the macaque monkey: input to ventral posterior nuclei

The distribution of retrogradely labeled spinothalamic tract (STT) neurons was analyzed in monkeys following variously sized injections of cholera toxin subunit B (CTb) in order to determine whether different STT termination sites receive input from different sets of STT cells. This report focuses on STT input to the ventral posterior lateral nucleus (VPL) and the subjacent ventral posterior inferior nucleus (VPI), where prior anterograde tracing studies identified scattered STT terminal bursts and a dense terminal field, respectively. In cases with small or medium-sized injections in VPL, labeled STT cells were located almost entirely in lamina V (in spinal segments consistent with the mediolateral VPL topography); few cells were labeled in lamina I (<8%) and essentially none in lamina VII. Large and very large injections in VPL produced marked increases in labeling in lamina I, associated first with spread into VPI and next into the posterior part of the ventral medial nucleus (VMpo), and abundant labeling in lamina VII, associated with spread into the ventral lateral (VL) nucleus. Small injections restricted to VPI labeled many STT cells in laminae I and V with an anteroposterior topography. These observations indicate that VPL receives STT input almost entirely from lamina V neurons, whereas VPI receives STT input from both laminae I and V cells, with two different topographic organizations. Together with the preceding observation that STT input to VMpo originates almost entirely from lamina I, these findings provide strong evidence that the primate STT consists of anatomically and functionally differentiable components.     

A quantitative study of spinothalamic neurons in laminae I, III, and IV in lumbar and cervical segments of the rat spinal cord

The major ascending outputs from superficial spinal dorsal horn consist of projection neurons in lamina I, together with neurons in laminae III-IV that express the neurokinin 1 receptor (NK1r) and have dendrites that enter the superficial laminae. Some neurons in each of these populations belong to the spinothalamic tract, which conveys nociceptive information via the thalamus to cortical areas involved in pain. A projection from the cervical superficial dorsal horn to the posterior triangular nucleus (PoT) has recently been identified. PoT is at the caudal end of the thalamus and was not included in injection sites in many previous retrograde tracing studies. We have injected various tracers (cholera toxin B subunit, Fluoro-Gold, and fluorescent latex microspheres) into the thalamus to estimate the number of spinothalamic neurons in each of these two populations, and to investigate their projection targets. Most lamina I and lamina III/IV NK1r-immunoreactive spinothalamic neurons in cervical and lumbar segments could be labeled from injections centered on PoT. Our results suggest that there are 90 lamina I spinothalamic neurons per side in C7 and 15 in L4 and that some of those in C7 only project to PoT. We found that 85% of the lamina III/IV NK1r-immunoreactive neurons in C6 and 17% of those in L5 belong to the spinothalamic tract, and these apparently project exclusively to the caudal thalamus, including PoT. Because PoT projects to second somatosensory and insular cortices, our results suggest that these are major targets for information conveyed by both these populations of spinothalamic neurons.     

Ascending and descending internuclear projections within the trigeminal sensory nuclear complex

The cells of origin of ascending and descending internuclear pathways in the trigeminal sensory nuclear complex were studied by the method of retrograde transport of horseradish peroxidase in the cat. The cells of origin of the ascending internuclear pathways are distributed in all laminae of the caudal part of the spinal trigeminal nucleus (Vc) except for lamina II and the caudal regions of the pars interpolaris of the spinal trigeminal nucleus (Vi). The cells arising from the Vc project to all rostral trigeminal nuclei except the caudal Vi and dorsal part of the principal trigeminal nucleus (Vpd), and neurons of the caudal Vi project to the dorsomedial (Vo.dm) and rostrodorsomedial (Vo.r) divisions of the spinal trigeminal nucleus and the ventral part of the principal trigeminal nucleus (Vpv), although the main ascending fibers from the Vc arise from laminae III-V and project to the rostral Vi and pars oralis. By contrast, the cells of origin of the descending internuclear pathways are distributed in all trigeminal nuclei, with chain-like connections between the neighboring nuclei, while the caudal regions of the Vi and laminae I-II do not receive any descending projections. The main ascending fibers from the paratrigeminal nucleus (or interstitial nucleus) at the caudal level of the Vi project to the parabrachial nucleus. These findings indicate that the internuclear pathways are differentially organized between the ascending and descending projections, and suggest that the internuclear trigeminal connections have a smaller influence on the trigeminothalamic tract cells in the Vpd, caudal Vi, and lamina I.     

Thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat

The topical organization of thalamic projections to the second and fourth somesthetic areas in the anterior ectosylvian gyrus of the cat has been studied using the technique of retrograde axonal transport of horseradish peroxidase. The projections of the posterolateral and posteromedial ventral nuclei (VPL, VPM) to the second somesthetic area (SII) are organized somatotopically. The posterior portion of SII (hindlimb area) receives fibers mainly from the dorsolateral part of VPL, the middle portion of SII (forelimb area) from the ventromedial part of VPL, and the anterior portion of SII (face area) from VPM. These topical projections are more loosely organized and less densely arranged than those to the first somesthetic area. The SII receives a few fibers from the medial geniculate nucleus, particularly its magnocellular and dorsal principal parts, and from the suprageniculate nucleus. The posterior part of SII lying near the secondary auditory area receives many fibers from the medial geniculate and suprageniculate nuclei, and only a few fibers from the lateral central and paracentral nuclei. The fourth somesthetic area (SIV), located in the dorsal bank of the anterior ectosylvian sulcus, receives fibers mainly from the dorsal principal and magnocellular parts of the medial geniculate nucleus, and from the suprageniculate nucleus. The SIV receives a fair number of fibers from VPL and VPM roughly in a somatotopical manner. The posterior portion of SIV receives fibers chiefly from the dorsolateral part of VPL, the middle portion of SIV from the ventromedial part of VPL, and the anterior portion from VPM. In addition, SIV receives a few fibers from the lateral central, paracentral, ventral lateral and ventral medial nuclei. The SIV, together with the most posterior part of SII, forms an auditory area, receiving many fibers from the medial geniculate and suprageniculate nuclei, and a few fibers from the intralaminar nuclei.     

Immunocytochemistry of enkephalin and serotonin distribution in restricted zones of the rostral trigeminal spinal subnuclei: comparisons with subnucleus caudalis

The spinal trigeminal subnucleus caudalis processes nociceptive input from the head. However, physiological and behavioral studies in monkeys and humans indicate that painful stimuli from the central face and oral cavity also project through trigeminal nuclei rostral to the spinal subnucleus caudalis. Both enkephalin (ENK) and serotonin (5-HT) are present in rostral trigeminal nuclei and these regions receive inputs from the raphe complex. Thus, it appears that elements of pain-modulating circuitry proposed by Basbaum and Fields (Annu. Rev. Neurosci., 7:309-338, 1984) for the spinal and medullary dorsal horn may also exist in this region. In order to begin an exploration of this circuitry, the present study combines the techniques of retrograde transport of HRP from the ventral posteromedial thalamic nucleus (VPM) of the cat's thalamus to label trigeminothalamic relay cells. Secondarily, immunocytochemical techniques are employed to define the distribution patterns of ENK and 5-HT cells and terminals in relationship to both labeled and nonlabeled neurons in each of the subnuclei of the spinal trigeminal nucleus. Trigeminothalamic relay cells were observed in laminae I and II, the magnocellular region, and the interstitial nucleus (IN) of subnucleus caudalis (Vc). ENK was found in axodendritic and axosomatic terminals, together with a population of small fusiform neurons in all these same areas except the magnocellular region. ENK axosomatic contacts innervated approximately 30% of labeled relay cells, chiefly in lamina I and the IN, or small unlabeled neurons in the same area. Serotonin activity occurred principally in lamina I and the IN and was confined almost exclusively to axodendritic terminals. Examination of subnucleus interpolaris (Vi) revealed relay cells distributed throughout the length of the nucleus and increasing in numbers at rostral levels. A rostral extension of the IN was found just ventrolateral to the main body of Vi and contained numerous labeled cells. The distribution of ENK activity was restricted to the ventral part of Vi and the IN and occurred in axodendritic and axosomatic terminals. These latter elements innervated 30-40% of labeled relay cells in Vi, particularly those located in the IN. Cells containing ENK generally resembled the fusiform cells found in Vc and were distributed in ventral Vi and the IN. Some ENK cells were larger, displayed several dendrites, and occurred only in the ventral Vi. Serotonin within Vi and Vc was confined principally to axodendritic terminals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.     

Thalamic connections of the ground squirrel superior colliculus and their topographic relations

The connections of the superior colliculus (SC) of the ground squirrel Spermophilus tridecemlineatus were studied with the horseradish peroxidase (HRP) method. Multiple pressure injections of HRP served to define the total pattern of SC projections while iontophoretic injections allowed differentiation of connections of the deep and superficial layers and determination of topographic relations of SC with its associated nuclei. The deep laminae were mainly connected with auditory, somatosensory and reticular regions of the brain, including the inferior colliculus, zona incerta, substantia nigra, mesencephalic central grey, pontine nuclei, spinal trigeminal nucleus, nucleus of the posterior commissure, thalamic reticular nucleus, raphe nuclei, lateral vestibular nucleus, the lateral superficial reticular formation of the medulla, the mesencephalic reticular formation, nucleus gracilis and the cervical spinal cord. The superficial laminae were connected with visual system structures. They were reciprocally connected with the dorsal and ventral lateral geniculate nuclei, the pretectum, nucleus lateralis posterior (LP), the parabigeminal nucleus and the contralateral SC. Connections between the SC and the dorsal lateral geniculate were topologic. LP was found to consist of three divisions: rostrolateral, rostromedial and caudal. SC was interconnected with the rostrolateral and caudal divisions. The connections between the SC and the rostrolateral division were topologic; those with the caudal division were not. The connections of the deep collicular layers in ground squirrels were similar to those which have been reported for cats and monkeys. The connections of the superficial laminae were more extensive than has been reported in other species. These elaborate interconnections indicate extensive interaction between primary retinal projection nuclei in the processing of visual information.     

Efferent projections from temperature sensitive recording loci within the marginal zone of the nucleus caudalis of the spinal trigeminal complex in the cat

The efferent projections from nucleus caudalis of the spinal trigeminal complex in cats were studied with retrograde and anterograde axonal transport techniques combined with localization of recording sites in the thalamus and marginal zone of nucleus caudalis to innocuous skin cooling. Results showed brainstem projections from nucleus caudalis to rostral levels of the spinal trigeminal complex, to the ventral division of the principal trigeminal nucleus, the parabrachial nucleus, cranial motor nuclei 7 and 12, solitary complex, contralateral dorsal inferior olivary nucleus, portions of the lateral reticular formation, upper cervical spinal dorsal horn and, lateral cervical nucleus. Projections to the thalamus included: a dorsomedial region of VPM (bilaterally) and to the main part of VPM and PO contralaterally. Neuronal activity was recorded in the dorsomedial region of VPM to cooling the ipsilateral tongue. HRP injections in this thalamic region retrogradely labeled marginal neurons in nucleus caudalis. These results show that marginal neurons of nucleus caudalis provide a trigeminal equivalent of spinothalamic projections to the ventroposterior nucleus in cats.     

Projections to the spinal cord from medullary somatosensory relay nuclei.

Descending projections to the spinal card from the dorsal column nuclei were studied in the cat, rat and monkey with the retrograde horseradish peroxidase (HRP) technique, and in the cat with the autoradiographic anterograde axonal transport technique. Retrogradely labeled neurons were seen in the dorsal column nuclei after HRP injections at all levels of the spinal cord and additionally in the magnocellular division of the spinal caudalis nucleus of the trigeminal nerve after injections into cervical spinal segments in all three species. HRP-positive neurons were predominantly located along the middle of the rostro-caudal axis of the dorsal column nuclei and amongst the fusiform, triangular and polygonal cells that surround, especially ventrally, the cell nest zone containing thalamic relay neurons. The labeled neurons are densely concentrated in those portions of the dorsal column nuclei where most corticofugal and non-primary afferent projections terminate and where the terminal distribution of primary afferent fibers is overlapping and diffuse. Previous studies have shown that most neurons in this middle and ventral region do not project to the thalamus or cerebellum. The majority of the cells in the dorsal column nuclei with descending axons or axon collaterals project by way of the ipsilateral dorsal columns, but some fibers project into the dorsolateral funiculus; the descending trigeminal fibers course in the dorsolateral funiculus. The terminal fields for these fibers in the cervical spinal cord include the lateral cervical nucleus, laminae IV and V, and possibly lamina I. These results indicate that the dorsal column nuclei may contribute to a feedback mechanism regulating the flow of sensory information ascending along other somatosensory spinal pathways.     

Central projections of primary sensory neurons innervating different parts of the vibrissae follicles and intervibrissal skin on the mystacial pad of the rat.

The cell bodies and central projections of neurons innervating the vibrissae follicles and adjacent skin in the rat were investigated by retrograde and transganglionic transport of HRP. The cell bodies of neurons innervating the vibrissa follicle via the deep vibrissa nerve (DVN) were the largest, followed by those innervating the follicle via the superficial vibrissa nerve (SVN). The smallest cell bodies were those innervating the intervibrissal skin. The DVN neurons terminated centrally as an almost uninterrupted column through the trigeminal sensory nuclear complex. The DVN projections to nucleus caudalis and C1 dorsal horn were entirely restricted to laminae III, IV, and V. Besides the projections to lamina V, the DVN projections were strictly localized somatotopically at all levels replicating the peripheral organization of the vibrissae. The SVNs projected sparsely to midlevels of the main sensory nucleus but not to nuclei oralis and interpolaris. The main SVN projections appeared in laminae I-III of nucleus caudalis. In addition, a small projection to lamina V was observed. The projections to laminae II and III were organized mediolaterally in a similar way as the DVN projections; those to laminae I and V were less restricted. The intervibrissal skin neurons projected sparsely to the caudal main sensory nucleus and to the border between nuclei oralis and interpolaris. The projections to nucleus caudalis were restricted to laminae I-III and V and were organized in a similar way as the SVN projections.     

Thalamic processing of vibrissal information in the rat. I. Afferent input to the medial ventral posterior and posterior nuclei.

Retrograde tracing with true blue (TB) and diamidino yellow (DY) and anterograde tracing with either wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) or Phaseolus vulgaris leucoagglutinin (PHA-L) were employed to investigate the projections from trigeminal nucleus principalis (PrV) and trigeminal subnucleus interpolaris (SpI) to their targets in the medial ventral posterior (VPM) and posterior (POm) nuclei of the thalamus. Many more cells in both PrV and SpI were labeled by tracer injections into VPM than into POm. Only a very small number of double-labeled neurons were observed in either PrV or SpI. However, a significantly higher percentage of SpI cells projected to POm or to both POm and VPM than was the case for PrV. Anterograde tracing with WGA-HRP showed that the projections from both PrV and SpI to VPM were much denser than those from the same nuclei to POm. Small injections of PHA-L into either PrV or SpI produced a focus of fairly dense labeling in VPM and much more diffuse terminal labeling in POm. These anatomical data provide evidence for two separate trigeminothalamic pathways, one originating from PrV and the second originating from SpI. Both of these pathways converge and diverge at the thalamic level. That is, information from the PrV pathway and from the SpI pathway are both provided to VPM in a morphologically restricted fashion and to POm in a morphologically widespread fashion.     

Spinal and trigeminal projections to the nucleus of the solitary tract: a possible substrate for somatovisceral and viscerovisceral reflex activation

This study used the retrograde transport of a protein-gold complex to examine the distribution of spinal cord and trigeminal nucleus caudalis neurons that project to the nucleus of the solitary tract (NST) in the rat. In the spinal grey matter, retrogradely labeled cells were common in the marginal zone (lamina I), in the lateral spinal nucleus of the dorsolateral funiculus, in the reticular part of the neck of the dorsal horn (lamina V), around the central canal (lamina X), and in the region of the thoracic and sacral autonomic cell columns. The pattern of labeling closely resembled that seen for the cells at the origin of the spinomesencephalic tract and shared some features with that of the spinoreticular and spinothalamic tracts. Labeled cells in lamina IV of the dorsal horn were only observed when injections spread dorsally, into the dorsal column nuclei, and are thus not considered to be at the origin of the spinosolitary tract. They are probably neurons of the postsynaptic fibers of the dorsal column. Retrogradely labeled cells were also numerous in the superficial laminae of the trigeminal nucleus caudalis, through its rostrocaudal extent. The pattern of marginal cell labeling appeared to be continuous with that of labeled neurons in the paratrigeminal nucleus, located in the descending tract of trigeminal nerve. Since the NST is an important relay for visceral afferents from both the glossopharyngeal and vagus nerves, we suggest that the spinal and trigeminal neurons that project to the NST may be part of a larger system that integrates somatic and visceral afferent inputs from wide areas of the body. The projections may underlie somatovisceral and/or viscerovisceral reflexes, perhaps with a significant afferent nociceptive component.     

The autoradiographic localization of substance P receptors in the rat and bovine spinal cord and the rat and cat spinal trigeminal nucleus pars caudalis and the effects of neonatal capsaicin

Substance P (SP) is a putative neurotransmitter in the central nervous system. In the present report we have used autoradiographic receptor binding techniques to investigate the distribution of SP receptor binding sites in the rat and bovine spinal cord and in the rat and cat spinal trigeminal nucleus pars caudalis. Although some quantitative differences were evident, all species appeared to have a similar distribution of SP receptor binding sites in both the spinal cord and in the spinal trigeminal nucleus pars caudalis. In the spinal cord the heaviest concentration of SP receptors is located in lamina X, while moderate to heavy concentrations were found in laminae I, II and V-IX. Very low concentrations of SP receptors were present in laminae III and IV. Examination of the cat and rat spinal trigeminal nucleus pars caudalis revealed a moderate density of SP receptor binding sites in laminae I and II, very low concentrations in laminae III and IV, and low to moderate concentrations in lamina V. Rats treated neonatally with capsaicin showed a small (11%) but significant (P < 0.02) increase in the levels of SP receptor binding sites in laminae I and II of the cervical and lumbar spinal cord while in all other laminae the levels remained unchanged.     

Subcortical projections to the centromedian and parafascicular thalamic nuclei in the cat

The primary objective of this study is to identify the totality of input to the centromedian and parafascicular (CM-Pf) thalamic nuclear complex. The subcortical projections upon the CM-Pf complex were studied in the cat with three different retrograde tracers. The tracers used were unconjugated horseradish peroxidase (HRP), horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), and rhodamine-labeled fluorescent latex microspheres (RFM). Numerous subcortical structures or substructures contained labeled neurons with all three tracing techniques. These labeled structures included the central nucleus of the amygdala; the entopeduncular nucleus; the globus pallidus; the reticular and ventral lateral geniculate nuclei of the thalamus; parts of the hypothalamus including the dorsal, lateral, and posterior hypothalamic areas and the ventromedial and parvicellular nuclei; the zona incerta and fields of Forel; parts of the substantia nigra including the pars reticularis and pars lateralis, and the retrorubral area; the pretectum; the intermediate and deep layers of the superior colliculus; the periaqueductal gray; the dorsal nucleus of the raphe; portions of the reticular formation, including the mesencephalic, pontis oralis, pontis caudalis, gigantocellularis, ventralis, and lateralis reticular nuclei; the nucleus cuneiformis; the marginal nucleus of the brachium conjunctivum; the locus coeruleus; portions of the trigeminal complex, including the principal sensory and spinal nuclei; portions of the vestibular complex, including the lateral division of the superior nucleus and the medial nucleus; deep cerebellar nuclei, including the medial and lateral cerebellar nuclei; and lamina VII of the cervical spinal cord. Moreover, the WGA-HRP and rhodamine methods (known to be more sensitive than the HRP method) revealed several afferent sources not shown by HRP: the anterior hypothalamic area, ventral tegmental area, lateral division of the superior vestibular nucleus, nucleus interpositus, and the nucleus praepositus hypoglossi. Also, the rhodamine method revealed labeled neurons in laminae V and VI of the cervical spinal cord.     

Mapping the effects of motor cortex stimulation on somatosensory relay neurons in the rat thalamus: Direct responses and afferent modulation

Single unit recordings were used to map the spatial distribution of motor (MI) cortical influences on thalamic somatosensory relay nuclei in the rat. A total of 215 microelectrode penetrations were made to record single neurons in tracks through the medial and lateral ventroposterior (VPM and VPL), ventrolateral (VL), reticular (nRt), and posterior (Po) thalamic nuclei. Single units were classified according to their: 1) location within the nuclei, 2) receptive fields, and 3) response to standardized microstimulation in deep layers of the forepaw-forelimb areas of MI cortex. For mapping purposes, only short latency (1-7 msec) excitatory neuronal responses to the MI cortex stimulation were considered. Percentages of recorded thalamic neurons responsive to the MI stimulation varied considerably across nuclei: VL: 42.6%, nRt: 23.0%, VPL: 15.7%, VPM: 9.3%, and Po: 3.9%. Within the VPL, most responsive neurons were found in "border" regions, i.e., areas adjacent to the VL, and (to a lesser extent) the nRt and Po thalamic nuclei. The same parameters of MI cortical stimulation were used in studies of corticofugal modulation of afferent transmission through the VPL thalamus. A condition-test (C-T) paradigm was implemented in which the cortical stimulation (C) was delivered at a range of time intervals before test (T) mechanical vibratory stimulation was applied to digit No. 4 of the contralateral forepaw. The time course of MI cortical effects was analyzed by measuring the averaged evoked unit responses of the thalamic neurons to the T stimuli, and plotting them as a function of C-T intervals from 5-50 msec. Of the 30 VPL neurons tested during MI stimulation, the average response to T stimulation was decreased a mean 43%, with the suppression peaking at about 30 msec after the C stimulus. This suppression was more pronounced in the VPL border areas (-52% in areas adjacent to VL and nRt) than in the VPL center (-25%).