Primary somatosensory cortex modulation of tactile responses in nucleus gracilis cells of rats

Corticofugal influences from the primary somatosensory cortex to the gracilis nuclei were studied with single unit recordings performed in urethane-anaesthetized rats. Two types of neurons were identified: low firing rate (LF) neurons, which could be activated antidromically by medial lemniscus stimulation; and high firing rate (HF) neurons. The effects of electrically stimulating the contralateral primary somatosensory cortex were studied in two situations: when the stimulated cortical area and specific gracilis cells had overlapping receptive fields and when the receptive fields of the cells and primary somatosensory cortex did not overlap. Cortical stimulation facilitated cortical and tactile responses in most gracilis neurons (68% and 58% for LF and HF neurons, respectively) with overlapping receptive fields. When receptive fields were different, cortical stimulation inhibited tactile response in most LF neurons (58%) and some HF neurons (20%). Trains of cortical shocks during sensory stimulation demonstrated that the facilitatory and inhibitory effects outlasted the stimulation period by 5 min. The facilitatory effect was decreased by iontophoretic application of the N-methyl-D-aspartate (NMDA) receptor antagonist APV (50 mm). However, APV did not modify the intensity of the tactile response inhibition in cells with nonoverlapping receptive fields, although, its duration was decreased (<5 min). Iontophoretic application of the gamma-aminobutyric acid (GABA)(A) antagonist bicuculline (20 mm) blocked the cortically evoked inhibition in cells with nonoverlapping receptive fields. The results indicate that the somatosensory cortex precisely controls somatosensory transmission throughout the gracilis nucleus by means of NMDA and GABA(A) receptor activation.     

Quantitative stereological evaluation of the gracile and cuneate nuclei and their projection neurons in the rat

Stereological methods were employed to estimate the volume and neuron numbers of the rat dorsal column nuclei (DCN). These methods were applied to Nissl-stained sections from control animals and cases that received injections of horseradish peroxidase in the thalamus, the cerebellum, or the spinal cord. Additional cases received combinations of fluorescent tracers in the same structures, to examine whether some of the retrogradely labeled neurons sent collaterals to different targets. The mean volume of the DCN is 0.81 mm(3) (range 0.65-1.10 mm(3)), of which 3%, 39%, and 59% correspond, respectively, to the nucleus of Bischoff (Bi), the gracile (Gr), and the cuneate (Cu) nuclei. Within Cu, the middle division (CuM) is the largest (42%), followed by the rostral (CuR; 36%) and caudal (CuC; 22%) divisions. The mean total number of neurons in the DCN is 16,000 (range 12,400-19,500), of which 2.4%, 34.0% and 63.6% correspond, respectively, to Bi, Gr, and Cu. Within Cu, CuM contains 48% of all neurons, and 27% correspond to CuR and 25% to CuC. Interanimal variability is moderate for the whole DCN and Cu but increases when individual nuclei are considered. About 80% of DCN neurons project to the thalamus, 3% to the spinal cord, and 7% to the cerebellum. Thalamic-projecting cells are more numerous in CuM and Gr (83%), and relatively less common in Bi and CuC (72-74%). Most of the DCN neurons projecting to the spinal cord appear in CuC and CuM. Two-thirds of the neurons projecting to the cerebellum are located in CuR, 20% in CuM, and 15% in Gr. A small fraction of neurons projects simultaneously to spinal cord and thalamus.     

Brainstem projections to the rat cuneate nucleus

Neurons in the pontomedullary tegmentum have been proposed as a final common pathway subserving descending inhibition in the dorsal column nuclei. To investigate the anatomical substrate for these descending effects, brainstem projections to the cuneate nucleus of rats were studied with injections of lectin-conjugated horseradish peroxidase. In rats with iontophoretic tracer injections in this nucleus, many labeled neurons were detected near the injection site, especially ventral and caudal to it. Intrinsic reciprocal projections were observed after injections in caudal, middle, or rostral levels of the cuneate nucleus. Neurons were labeled in the red nucleus, in agreement with previous anatomical studies, and also in the trigeminal, vestibular, and cochlear nuclei. An ipsilateral dorsomedial group of neurons was labeled in the upper cervical segments and scattered neurons were also labeled bilaterally near the central canal. Sparse retrograde labeling in the tegmentum was focused in the lateral paragigantocellular nucleus and caudal raphe. Consistent with the retrograde experiments, anterograde labeling after pressure injections of lectin-conjugated horseradish peroxidase in the pontomedullary tegmentum was very sparse within the dorsal column nuclei; labeling was dense, however, in the region immediately ventral to these nuclei. These results confirm previous work indicating that the activity of cuneate neurons is modulated by brainstem sensory nuclei. However, it appears that direct projections to the cuneate nucleus from pontine and rostral medullary regions are sparser than previously suggested. The last link of a polysynaptic descending inhibitory pathway may include GABAergic neurons immediately adjacent to the dorsal column nuclei and/or intrinsic to these nuclei.     

Projections of digit afferents to the cuneate nucleus in the raccoon before and after partial deafferentation

Within the cuneate nucleus of the raccoon, the representations of individual forepaw digits are anatomically separated by densely myelinated laminae. This unique arrangement was utilized to determine whether the terminations of cutaneous afferents from individual digits are precisely restricted to the appropriate region of the cuneate nucleus or overlap with afferents from adjacent digits. By using the transganglionic transport of horseradish peroxidase (HRP), it was found that, for each digit, the terminal labeling was restricted to the appropriate 150-250-micron-wide column that extended rostrocaudally throughout the nucleus. The topographical arrangement of digit input corresponded to the known electrophysiology, with the terminal column for the fifth digit located most medially within the nucleus and those for digits 4 to 1 successively more laterally. Within a column, the density of labeling was greater over cell clusters than between clusters. These results indicate that afferents from adjacent digits do not overlap in the cuneate nucleus. In six animals, the fifth digit was amputated, and 2-4 months later, HRP was injected into the nerves of the fourth digit to determine whether its afferents had sprouted into the denervated fifth-digit column. The projection pattern from the fourth digit in each of these animals was the same as in normal animals and the same as in the intact contralateral side. These results indicate that the reorganization seen in the cerebral cortex following peripheral deafferentation cannot be attributed to changes in the afferent fiber projections to the cuneate nucleus.     

Caudal cuneate nucleus projection to the direct thalamic relay to the motor cortex: an electrophysiological study

We previously reported that injection of horseradish peroxidase (HRP) into a physiologically identified region of the thalamus between the ventrolateral nucleus and ventroposterolateral nucleus, VL-VPL, in cat results in labeled cell bodies in the caudal cuneate nucleus (CCN) of the dorsal column nuclei (DCN). We recognized, however, that the spread of HRP to localized regions of less than 1.0 mm distance from the injection site and subsequent uptake by neighboring fibers might have accounted for the resulting label in CCN. In the present study, therefore, we reexamined the DCN input to VL-VPL using a more sensitive physiological method. First, we used the microstimulation technique and corroborated the previous result. In 5 additional preparations, a modified collision procedure was used to ascertain that the same VL-VPL neuron which projects to the motor cortex also receives input from CCN. We report, for the first time, evidence of a lemniscal input to neurons in VL-VPL which are physiologically identified as projecting to the motor cortex.     

Representation of the body surface in the gracile,cuneate, and spinal trigeminal nuclei of the little red flying fox (Pteropus scapulatus)

The body surface representation in the gracile, cuneate, and spinal trigeminal nucleil of the little red flying fox (Pteropus scapulatus) was examined. As in other species, it was found that any single cross-section through all three nuclei contains a representation of most, or all, of the body surface. In the little red flying fox, however, this representation is arranged as a series of dorsolateral to ventromedially oriented bands, within which there are no apparent topographies. These bands are arranged in such a way that the spatial relationships between body regions in the representation do not reflect those at the periphery. © 1993 Wiley-Liss, Inc.     

Interactions of ventral tract and dorsal column inputs into the cat cuneate nucleus

In decerebrate- decerebellate cats with spinal lesions separating the dorsal column (DC) from the spinocervicothalamic and ventral tract (VT) pathways, conditioning VT stimulation activated a few, but inhibited most, of the cuneate neurons discharging to test DC stimulation. This VT input into the cuneate nucleus is mediated through the brain stem.     

Somatosensory properties of cuneocerebellar neurones in the main cuneate nucleus of the rat

Cells in the main cuneate nucleus (MCN) are known to provide a direct projection to the cerebellum, but the precise nature of the information these cells transmit to the cerebellum is unknown. The present study employed anatomical and electrophysiological procedures to determine the location of cuneocerebellar cells in the MCN, and their somatosensory properties in the rat. The location of neurones projecting to the cerebellum was determined with injections of the retrograde tracers, horseradish peroxidase or Fluoro-Gold in vermal and paravermal regions of the cerebellum. Topographically, the majority of retrogradely labelled cells in the MCN were found to lie primarily ventrolateral in the nucleus and rostral to the level of the obex. Single unit recordings from 69 well characterized MCN cells, identified as projection cells by antidromic activation from stimulation of the inferior cerebellar peduncle, were classified according to their responses to cutaneous stimulation and manipulation of joints and muscles. A slight majority of cells (37.7%) responded only to manipulation/stimulation of joints, and 30.4% of cells responded only to cutaneous stimulation. The remaining cells received convergent input from joint and cutaneous receptors. Cutaneous responsive cells all rapidly adapted to maintained stimuli, and had large receptive fields (RFs) that were generally located over the joints. These cells could be activated by passive movements of the forelimb that deformed the RF. They only discharged during movements and were silent during maintained limb positions. Cells responsive to punctate mechanical stimuli applied to the joint capsules, responded to passive movements of the forelimb, but typically only discharged towards the limits of joint movement, and adapted within a few seconds. Once adapted, small perturbations of joint position resulted in vigorous dynamic responses. The results indicate that the neurones in the MCN of the rat which project directly to the cerebellum are localized in the rostral half of the nucleus. They transmit predominantly dynamic information from joint and cutaneous receptors that are likely to be normally activated as a result of limb movements. These cells could signal information about evolving movements or disturbances of forelimb posture or stance.     

Somatosensory and auditory relay nucleus in the rostral part of the ventrolateral medulla: a morphological study in the cat

A nucleus that possibly relays both somatosensory and auditory information was identified in the well-known autonomic control region in the rostral part of the ventrolateral medulla (RVL) of the cat by four sets of experiments using the WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate) method. First, after injecting WGA-HRP into the dorsal column nuclei (DCN), anterograde and retrograde labeling was found bilaterally within and around a small cluster of medium-sized neurons in the RVL; more labeled neuronal cell bodies were seen in the cluster ipsilateral to the injection than in the contralateral cluster, whereas labeled axon terminals were distributed more densely on the contralateral side than on the ipsilateral side. The neuronal cluster in the RVL was located close to the ventrolateral surface of the medulla oblongata, constituting a short, slender column extending from a caudal level of the facial nucleus to the level of the rostral one-third of the inferior olive. This cluster of neurons was named the ventrolateral medullary nucleus (VLMN). In the second set of experiments, WGA-HRP was injected into the VLMN. Labeled neuronal cell bodies were seen in the reticular zone of the DCN bilaterally, with a slight dominance on the side contralateral to the injection, and further in the anteroventral division of the cochlear nuclei (CN) bilaterally, with a predominantly contralateral distribution. Labeled presumed axon terminals were seen bilaterally not only in the DCN and granular layer of the CN but also in the intercollicular region (IcR), lateral division of the posterior group of the thalamus (Pol), and medial geniculate nuclei (MG). Labeled terminals in the DCN were more numerous on the side ipsilateral to the injection than on the contralateral side, whereas those in other regions were distributed with a clear-cut contralateral dominance. In the third set of experiments, WGA-HRP injection into the CN resulted in anterograde and retrograde labeling in the VLMN. The labeling was bilateral, but more marked in the VLMN contralateral to the injection. In the fourth set of experiments, after WGA-HRP injection into the IcR, Pol, or MG, labeled neuronal cell bodies were located in the VLMN bilaterally with a dominant contralateral distribution. The results indicate that the VLMN possibly relays somatosensory and auditory information from the reticular zone of the DCN and anteroventral division of the CN to the IcR, Pol, and MG.     

Bilateral effects of spinal overhemisections on the development of the somatosensory system in rats

Connections of the forepaw regions of somatosensory cortex (S1) were determined in rats reared to maturity after spinal cord overhemisections at cervical level C3 on postnatal day 3. Overhemisections cut all ascending and descending pathways and intervening gray on one side of the spinal cord and the pathways of the dorsal funiculus contralaterally. Bilateral lesions of the dorsal columns reduced the size of the brainstem nuclei by 41%, and the ventroposterior lateral subnucleus (VPL) of the thalamus by 20%. Bilateral lesions also prevented the emergence of the normal cytochrome oxidase barrel pattern in forepaw and hindpaw regions of S1. Injections of wheat germ agglutinin conjugated to horseradish peroxidase were placed in the forepaw region of granular S1 and surrounding dysgranular S1 contralateral to the hemisection. The VPL nucleus was densely labeled, whereas the adjoining ventroposterior medial subnucleus, VPM, representing the head, was unlabeled. Thus, there was no evidence of abnormal connections of VPM to forepaw cortex. Foci of transported label in the ipsilateral hemisphere appeared to be in normal locations and of normal extents, but connections in the opposite hemisphere were broadly and nearly uniformly distributed in sensorimotor cortex in a pattern similar to that in postnatal rats. Rats with incomplete lesions that spared the dorsal column pathway on the left side but not the right demonstrated surprisingly normal distributions of callosal connections in the nondeprived right hemisphere, even though the injected left hemisphere was deprived. Thus, the development of the normal pattern of callosal connections depends on dorsal column input and not on normal interhemsipheric interactions.     

Representation of the forepaw in the feline cuneate nucleus: a transganglionic transport study

The projection of forelimb nerves innervating the paw to the cuneate nucleus was studied in the cat by the transganglionic transport method. Exposure of a single digital nerve to the tracer (a conjugate of horseradish peroxidase to wheat-germ agglutinin) resulted in a longitudinal sequence of labeled patches throughout the extent of the nucleus. In the middle region the labeled patches coincided with the location of the cell clusters that are characteristic of this part of the nucleus. A very precise somatotopic termination pattern was found in the middle region of the nucleus. Afferent fibers from the palm were represented superficially close to the dorsal rim. The digits were represented in a mediolateral sequence, with the first digit in the dorsolateral part of the nucleus and the fifth digit in the dorsomedial part. The ventral surfaces of the digits were represented superficial to the dorsal surfaces. The dorsum of the paw was represented close to the center of the nucleus. A similar somatotopic organization, but much less detailed, was found in the rostral and caudal regions of the cuneate nucleus. These dissimilarities in somatotopic detail between the different cytoarchitectonic regions of the cuneate nucleus probably reflect differences in function between these regions.     

Medullary sources of projections to the kinesthetic thalamus in raccoons: external and basal cuneate nuclei and cell groups x and z

In raccoons and other mammals, a pathway for kinesthetic sensation (from muscles, fascia, tendons, and joints) reaches the anterodorsal cap of the ventrobasal thalamus and the anteriormost part of the somatic sensory cerebral cortex. To find the medullary component of this kinesthetic pathway in raccoons, small injections of horseradish peroxidase were made in the thalamus under guidance of simultaneous electrophysiological recording from kinesthetic projections. As determined by retrograde labeling following these injections, kinesthetic thalamic subregions receive projections as follows: caudomedial from cells in the external cuneate nucleus and its medial tongue, rostromedial from cells in basal cuneate nucleus, and rostrolateral from cells in cell group z and the reticular division of cell group x. Electrophysiological recording showed kinesthetic representations in each of these medullary regions. Labeled cells were also observed in the infratrigeminal subnucleus of the lateral reticular nucleus. Cats have kinesthetic projections to the thalamus from the basal cuneate and cell group z; raccoons (and monkeys) have these plus projections from the external cuneate and cell group x. This suggests that the kinesthetic projection system in raccoons and monkeys is expanded in correlation with their more dextrous use of the hand.     

Comparison of reorganization of the somatosensory system in rats that sustained forelimb removal as neonates and as adults

Studies of sensory pathways in several species indicate that the extent and form of reorganization resulting from deafferentation early in life vs. adulthood are not the same. The reasons for such differences are not well understood. To gain further insight into age-dependent mechanisms of reorganization, this study compared the consequences of neonatal vs. adult forelimb amputation in rats at multiple levels of the sensory pathway, including primary somatosensory cortex, brainstem, and dorsal root ganglia. At the cortical level, the average area of the functional forelimb-stump representation from rats amputated as adults was significantly smaller (P < 0.05) than that of neonatally amputated rats (4.3 +/- 1.3 mm(2) vs. 6.6 +/- 1.5 mm(2), respectively). At the brainstem level, neonatally amputated rat cuneate neurons possessed the following responsivities: 20% stump responsive, 40% responsive to both stump and hindlimb, 30% responsive to another body region, and 10% unresponsive. In contrast, cuneate neurons of adult amputated rats were 70% stump responsive, 2% responsive to both stump and hindlimb, and 30% unresponsive. A significantly (P < 0.001) greater percentage of the C(6)-C(8) dorsal root ganglia neurons of adult amputated rats were unresponsive to peripheral stimulation vs. neurons from neonatally amputated rats (48% vs. 16%, respectively). These results indicate that the reorganization that occurs in response to forelimb amputation at birth vs. adulthood is distinctly different at each of these levels of the dorsal column-medial lemniscal pathway. Possible mechanisms to account for these differences are considered.     

Nucleus z in the rat: spinal afferents from collaterals of dorsal spinocerebellar tract neurons

Proprioceptive information from the hindlimb of the cat is now known to be relayed to the somatosensory thalamus and cortex via axons in the dorsolateral fasciculus and a medullary relay in nucleus z. The aim of this study was to identify nucleus z in the rat, to locate the cells of origin of spinal afferents to nucleus z, and to determine whether they are collaterals of the dorsal spinocerebellar tract. The location and extent of nucleus z were studied by filling the axon terminals of collaterals of the dorsal spinocerebellar tract (dsc) with horseradish peroxidase (HRP), which was injected into the inferior cerebellar peduncle. Nucleus z in the rat was found to be similar in location to nucleus z in other mammals. It was located just below the dorsal surface of the medulla, bounded laterally by the rostral pole of the cuneate nucleus and medially by the nucleus of the solitary tract. The cells of origin of the spinal afferents to nucleus z were studied by using the retrograde transport of HRP. They were located in Clarke's column (dorsal nucleus) and in lamina 10 of the dorsal horn. They were similar in location and morphology to neurons giving rise to the dorsal spinocerebellar tract, but were smaller in average diameter. A double retrograde labeling technique was used to determine whether the spinal afferents to nucleus z are collaterals of neurons giving rise to the dsc. It was estimated that up to 92% of the spinal afferents to nucleus z were collaterals of dsc neurons, while approximately 3% of all dsc neurons gave rise to collaterals terminating in nucleus z.     

Studies on the evolution of multiple somatosensory representations in primates: the organization of anterior parietal cortex in the New World Callitrichid, Saguinus

Because members of the New World family, Callithricidae, are generally regarded as the most primitive of monkeys, we studied the organization of somatosensory cortex in the tamarin (Saguinus) in hopes of better understanding differences in the organization of anterior parietal cortex in primates and how these differences relate to phylogeny. In most prosimian primates only one complete representation of cutaneous receptors has been found in the region of primary cortex, S-I, while in all Old and New World monkeys studied to date, two cutaneous representations exist in distinct architectonic fields, areas 3b and 1. In detailed microelectrode mapping studies in anesthetized tamarins, only one complete representation responsive to low-threshold cutaneous stimulation was evident in the S-I region. This topographic representation was in a parietal koniocortical field that architectonically resembles area 3b of other monkeys, and the general somatotopic organization of the field was similar to that of area 3b of other monkeys. Cortex rostral to the single representation was generally unresponsive to somatosensory stimuli, or required more intense stimulation for neural activation. Cortex caudal to the representation, in the region of area 1 of other monkeys, was generally either unresponsive or responded to only high-threshold stimulation, although some recording sites were activated by low-threshold tactile stimulation. The present evidence, together with that from previous studies, suggests that the single, complete body surface representation in Saguinus is homologous to the S-I representation found in some prosimians (Galago, Perodicticus) and the area 3b cutaneous representation found in New World Cebidae (Aotus, Saimiri, and Cebus) and Old World Macaca. Cortex rostral to S-I in Saguinus has the appearance of areas 3a and 4 of other primates. The cortex caudal to S-I in Saguinus, while resembling area 1 in some ways, does not have all of the features of area 1 of other monkeys. In particular, the field was not easily activated by low-threshold cutaneous stimuli, as area 1 is in other monkeys, and therefore a second cutaneous representation of all body parts was not demonstrated. Thus, cortex in the expected location of area 1 of Saguinus was not as responsive as area 1 of other monkeys, and it somewhat resembled the high-threshold fringe zones found caudal to S-I in anesthetized prosimians and some nonprimates. The results raise the possibility that the area 1 cutaneous representation that is characteristic of other New World monkeys and Old World monkeys evolved from a less responsive precursor along the caudal border of S-I in early monkeys.     

Topographical organization of pathways from somatosensory cortex through the pontine nuclei to tactile regions of the rat cerebellar hemispheres

The granule cell layer of the cerebellar hemispheres contains a patchy and noncontinuous map of the body surface, consisting of a complex mosaic of multiple perioral tactile representations. Previous physiological studies have shown that cerebrocerebellar mossy fibre projections, conveyed through the pontine nuclei, are mapped in registration with peripheral tactile projections to the cerebellum. In contrast to the fractured cerebellar map, the primary somatosensory cortex (SI) is somatotopically organized. To understand better the map transformation occurring in cerebrocerebellar pathways, we injected axonal tracers in electrophysiologically defined locations in Sprague-Dawley rat folium crus IIa, and mapped the distribution of retrogradely labelled neurons within the pontine nuclei using three-dimensional (3-D) reconstructions. Tracer injections within the large central upper lip patch in crus IIa-labelled neurons located centrally in the pontine nuclei, primarily contralateral to the injected side. Larger injections (covering multiple crus IIa perioral representations) resulted in labelling extending only slightly beyond this region, with a higher density and more ipsilaterally labelled neurons. Combined axonal tracer injections in upper lip representations in SI and crus IIa, revealed a close spatial correspondence between the cerebropontine terminal fields and the crus IIa projecting neurons. Finally, comparisons with previously published three-dimensional distributions of pontine neurons labelled following tracer injections in face receiving regions in the paramedian lobule (downloaded from http://www.rbwb.org) revealed similar correspondence. The present data support the coherent topographical organization of cerebro-ponto-cerebellar networks previously suggested from physiological studies. We discuss the present findings in the context of transformations from cerebral somatotopic to cerebellar fractured tactile representations.     

Functional relationship between somatosensory cortex and specialized afferent pathways in the monkey

Previous work showed that the primate dorsal funiculus (DF) was necessary for tactile discrimination which entailed movement. The extra-DF spinal afferent fibers, by contrast, were sufficient for discrimination of tactile stimuli which did not require movement. This study investigated the association between various cortical regions and the specialized tactile roles of the separate afferent systems. Monkeys learned two sets of tasks, one of which was dependent on DF integrity, and the other was capable of mediation by the extra-DF pathways. The cortical distribution and processing of DF and extra-DF information has been defined here by whether or not these tasks were affected by lesions in the respective regions. Lesions in area 3b led to impairment of both tasks, but more severe and longer-lasting impairment of the DF tests. Lesions in areas 1, 5, or 7 were without effect on either type of function. Ablation of the forelimb region in area 2 selectively damaged only the DF discriminations. These results, in combination with the results of others which are considered here, suggest that (i) both the DF and the extra-DF tactile information converge into area 3b; (ii) the extra-DF information is then projected diffusely to widespread regions of the cortex which enables it to survive limited parietal ablations; and (iii) the DF information is transmitted compactly to a focal region in area 2.