Gernot S. Doetsch

Functional reorganization of adult raccoon somatosensory cerebral cortex following neonatal digit amputation

Amputation of a forepaw digit in raccoons 2-8 weeks of age produced dramatic changes in the functional organization of somatosensory cortex examined electrophysiologically 9-12 months later. The cortical region normally representing the digit that was amputated received widely overlapping input from the entire forepaw, with local disruption of somatotopic organization. Compared with normal animals, the receptive fields of cortical neurons in amputated animals were larger, often included both glabrous and hairy skin, sometimes involved discontinuous skin regions, and were much more variable in peripheral location as a function of recording distance across the cortex and of depth within the cortex.

Short-term plasticity in primary somatosensory cortex of the rat: rapid changes in magnitudes and latencies of neuronal responses following digit denervation

Recordings were made from neurons in primary somatosensory (SmI) forepaw cortex of rats to study the time course of changes in responses beginning immediately following denervation (ligation) of a single digit. Before denervation, neuronal receptive fields (RFs) defined by tactile stimulation varied in size from small regions of one digit to larger areas covering several digits and palmar pads. With electrical stimulation, most neurons responded best to one (on-focus) digit and less to other (off-focus) digits; on-focus stimulation yielded more spikes per stimulus and shorter spike latencies (Lmin) than did off-focus stimulation. After ligation of the on-focus digit, most neurons showed increased responsiveness to stimulating one or several off-focus digits and palmar regions of the forepaw: (1) tactile stimulation showed that the RFs of all but one neuron expanded to include previously “ineffective” skin regions, such as digits or palmar pads adjoining the original RF; (2) electrical stimulation usually evoked stronger responses from neighboring off-focus digits and sometimes elicited novel responses from previously ineffective digits — seven of ten neurons showed increases in spikes per stimulus, which tended to approach stable values within 60–90 min after denervation; three of ten neurons showed decreases in Lmin with time, but most revealed no significant changes. These results suggest that dynamic response properties, as well as RFs, of SmI cortical neurons can be modified rapidly by blocking afferent input from dominant on-focus skin regions. RFs expand and novel responses appear, with concomitant increases in response magnitude and, in some cases, decreases in response latency over time. These findings seem to reflect a rapid increase in synaptic efficacy of weak or previously ineffective inputs from cutaneous afferent nerve fibers.

Coding of stimulus location and intensity in populations of mechanosensitive nerve fibers of the raccoon: I. Single fiber response properties

The primary aim of this study was to determine and compare the receptive field (RF) characteristics and response properties of single mechanosensitive nerve fibers innervating the glabrous skin of the forepaw and hindpaw of the raccoon. The action potentials of 129 median nerve fibers and 61 posterior tibial nerve fibers were recorded in response to punctate mechanical stimuli varying in location and intensity. The stimuli were delivered to six standard test sites on digit 1 and the contiguous pads of each paw. Attempts were made to classify each fiber according to its rate of adaptation to sustained stimulation; the RF of each fiber was mapped using a standard series of stimulus intensities. The results indicated that the response properties of individual fibers were highly complex and depended on the location and intensity of stimulation. 1) The distributions of absolute threshold were not different for the median or tibial nerve fibers or for different classes of fibers based on adaptation rate. A distal to proximal increase in threshold was found for each paw, suggesting a corresponding gradient of sensitivity across the glabrous skin. 2) Threshold RF areas did not vary across either paw nor did they differ between the two paws. Suprathreshold RFs were quite large relative to expected tactile acuity and displayed complex features. 3) Response properties such as adaptation rate, on- and off-responses, were found to vary with both stimulus location and intensity. It was concluded that the responses of individual nerve fibers could not uniquely encode any stimulus parameter tested, and that the properties of single fibers could not account for apparent differences in tactile acuity across each paw or between the two paws.

Progressive changes in cutaneous trigger zones for sensation referred to a phantom hand: a case report and review with implications for cortical reorganization

The dominant model of cortical plasticity induced by peripheral denervation suggests that a physiologically-reorganized cortical area can acquire new perceptual meaning, including a change in the peripheral referral of sensation. An alternative view is that such an area may retain its former perceptual significance, even though it becomes responsive to new peripheral inputs. To examine evidence related to this issue, a clinical case is presented documenting the time course of changes in phantom limb sensation in a patient with accidental amputation of a hand. About 24 h after injury, a vivid phantom hand was present; tactile stimulation revealed cutaneous trigger zones on the arm, stimulation of which elicited sensation referred to specific fingers of the phantom. While the phantom hand percept remained fairly stable over time, the trigger zones expanded progressively in size during the next 1-8 weeks but had contracted and changed location considerably about one year later. At all times studied, the trigger zones were topographically related to specific fingers and other parts of the phantom hand. The implications of these and other recent clinical findings for cortical reorganization are discussed, and the following tentative conclusions are drawn. (1) A phantom percept is mediated by central neural networks which remain functionally intact after amputation. (2) Cutaneous trigger-zones mapped in humans correspond to novel receptive fields of cortical neurons mapped in animals following peripheral denervation. (3) Cortical reorganization induced by denervation does not produce a major change in perceptual meaning or peripheral reference. In the present case, stimulation of new trigger zones (receptive fields) on the patients arm presumably activated a reorganized cortical hand area but evoked sensation still referred to the (now missing) hand. Hence, physiological cortical remapping is not necessarily accompanied by functional respecification.

Physiological changes in the somatosensory forepaw cerebral cortex of adult raccoons following lesions of a single cortical digit representation

The purpose of this study was to determine whether restricted lesions within primary somatosensory (SmI) cortex cause changes in the functional organization of cortical areas bordering on the site of injury. Focal ablations of cortical tissue were made in the representational area for digit 3 within the SmI forepaw cortex of adult raccoons. Electrophysiological mapping experiments done 15-17 weeks later showed that significant alterations had occurred in the response properties of clusters of neurons within those representational zones adjoining the lesion--the zones for digit 2, digit 4, and the palmar pads. These three cortical areas were modified by the appearance of new, usually weaker secondary inputs and changes in some properties of the normal primary inputs from the forepaw. (i) Many neurons responded to stimulation of previously ineffective skin regions; the new inputs often originated from digit 3 but frequently involved other digits or the pads as well. (ii) Neuronal receptive fields (RFs), mapped at a standard suprathreshold stimulus intensity, were larger than normal. (iii) Skin type and submodality sensitivity typically were less specific than normal; more neurons had RFs that included both glabrous and hairy skin or claws and displayed mixtures of responsiveness to skin touch, hair deflection, or claw touch. (iv) The representation of RF location, skin type, and submodality sensitivity was more variable as a function of horizontal and vertical distance through the cortex. In general, the physiological changes were found to degrade the somatotopic order and response specificity of the intact cortical areas adjoining the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactivity for GAD and Three Peptides in Somatosensory Cortex and Thalamus of the Raccoon

Immunocytochemical methods were used to determine the distributions of glutamic acid decarboxylase (GAD), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), and somatostatin (SOM) in the primary somatosensory cortex and somatosensory thalamus of adult raccoons. The cortex showed extensive immunoreactivity for GAD, revealing a large population of GABAergic neurons. GAD-labeled cells were numerous in all cortical layers, but were most concentrated in laminae II-IV. The cells were nonpyramidal and of varying morphology, typically with somata of small or medium size. GAD-immunoreactive puncta, presumably synaptic terminals, were widespread and often appeared to end on both GAD-negative and GAD-positive neurons. Immunoreactivity for the peptides was much less extensive than that for GAD, with the number of labeled neurons for VIP > CCK > SOM. Peptidergic cells were preferentially located in the upper and middle cortical layers, especially laminae II and III. The cells were nonpyramidal, often bitufted or bipolar in morphology, and small to medium in size. Their processes formed diffuse plexuses of fibers with terminal-like varicosities that occasionally surrounded nonpeptidergic neurons. The thalamus showed a clearly differentiated pattern of immunoreactivity for GAD, but little or no labeling for the three peptides. Nuclei adjoining the ventral posterior lateral (VPL)/ventral posterior medial (VPM) complex--including the reticular nucleus--contained many GAD-positive neurons and fibers. In contrast, the VPL and VPM nuclei displayed considerably less GAD immunoreactivity, somewhat surprising given the raccoons highly developed somatosensory system. However, the ventral posterior inferior (VPI) nucleus revealed rather dense GAD labeling, perhaps related to a specialized role in sensory information processing. Thus, the primary somatosensory cortex of the raccoon showed patterns of immunoreactivity for GAD and peptides that were similar to those of other species; the somatosensory thalamus revealed a distinctive profile of GAD immunoreactivity, with labeling that was light to moderate in the VPL/VPM complex and relatively extensive in VPL.

Functional properties of nerve fibers innervating cutaneous corpuscles within cephalic skin of the Texas rat snake

Abstract The functional properties of specialized cutaneous corpuscles found within the cephalic integument of the Texas rat snake were studied. The surface morphology of each of these end organs consisted of a rimmed, crater-like structure with a prominent peg protruding from the center of the crater. These surface features were directly associated with an underlying corpuscle which evaginated into the epidermis as a dermal papilla. The inner portion of the corpuscle contained a number of central cells with variously oriented cytoplasmic processes. Three or four myelinated nerve fibers were found near the base of the corpuscle; each fiber became unmyelinated as it entered the corpuscle and then divided into two or three smaller branches which terminated near the apex of the end organ. To determine whether or not these corpuscles might be specialized mechanoreceptors, the functional properties of 146 single maxillary nerve fibers innervating the corpuscle-rich supralabial scales of the Texas rat snake were studied. Twenty-one of these fibers (14%) were exclusively sensitive to mechanical stimulation of corpuscles, and were classified as “corpuscle units”; the other 125 fibers (86%) responded to mechanical stimulation of skin surrounding the corpuscles. Each corpuscle fiber was found to innervate from four to 13 individual corpuscles, with a mean of eight end organs per fiber. The adequate stimulus of these receptor units was lateral deflection of the central peg protruding from the crater of each corpuscle. Initial displacement of the peg from its vertical axis evoked a single “on” spike discharge; no response was elicited during sustained pressure exerted against the peg. When the peg was allowed to rebound to its original position, a single “off” impulse was usually elicited. Each fiber was optimally excited by moving mechanical stimuli across the surface of all corpuscles innervated by that fiber; the number of evoked spikes was directly related to the number of corpuscles stimulated. No directional preference for stimulus movement was found. All receptor units faithfully discharged one impulse during each cycle of a 256-Hz vibratory stimulus. Both the morphologic and electrophysiologic data indicated that the cutaneous corpuscles are structurally and functionally unique mechanoreceptors.

Distribution of neurons immunoreactive for parvalbumin and calbindin in the somatosensory thalamus of the raccoon.

The aim of this study was to assess the distribution of neurons immunoreactive for parvalbumin (PV), calbindin (CaBP), glutamic acid decarboxylase (GAD), and γ‐aminobutyric acid (GABA) in the somatosensory thalamus of the raccoon and to compare these features to those of other species, especially primates. Immunohistochemistry was used to study the location of these neurons in the ventroposterior nucleus (VP), ventroposterior inferior nucleus (VPI), posterior group of nuclei (Po), and reticular nucleus (Rt). A consistent differential pattern of PV‐positive (PV+) and CaBP‐positive (CaBP+) cells was found in the somatosensory thalamus. Many PV+ neurons were observed in VP and Rt, but very few were found in VPI or Po. In contrast, CaBP+ neurons were distributed throughout VP, VPI, and Po but were very sparse or absent in Rt. In the VP nucleus, PV+ cells were distributed in clusters separated by interclusteral regions with a sparse distribution of PV+ cell bodies. The distributions of PV+ and CaBP+ cells tended to be complementary to each other in VP; regions with a high density of PV+ neurons had a low density of CaBP+ cell bodies. Double‐labeling experiments revealed very few neurons in which PV and CaBP immunoreactivities were colocalized. Cells immunoreactive for GAD or GABA were found in PV‐dense clusters of VP; fewer GABAergic neurons were present in the CaBP‐dense interclusteral regions of VP and in VPI and Po. GAD+ and GABA+ neurons were most prominently distributed in Rt. We conclude that the distributions of PV+ and CaBP+ cell bodies in the raccoon somatosensory thalamus are very similar to those in primates. The density of GABAergic neurons in the somatosensory thalamus of the raccoon is less than that in the cat and monkey, but the relative distribution of GABAergic neurons in the different somatosensory nuclei is very similar to that in the cat and monkey. These results are discussed in relation to findings in other species and are related to the functions of lemniscal and nonlemniscal somatosensory pathways. J. Comp. Neurol. 388:120–129, 1997.

Population response characteristics of neurons in anterior motorsensory cerebral cortex (field 6) of the domestic cat

Summary In cats anesthetized with chloralose, extracellular recordings were obtained from neurons within cytoarchitectonic field 6aβ of motorsensory cerebral cortex. Hunting stimuli were electrical shocks delivered successively to the central footpad of each of the four paws. Many neurons were encountered which did not respond to such stimulation; however, 96 excitable neurons were isolated and studied. Unlike the situation in fields 4γ and 3b, all of the excitable neurons in field 6aβ were members of the samem subset, responsive to electrical stimulation of each paw; 7% were identified as pyramidal tract cells. Likem neurons elsewhere, those in field 6aβ were distributed throughout the lower two-thirds of the cortex, and were concentrated in layer V. In contrast to field 4γ and 3b,m neurons in field 6aβ showed uniformly lower discharge probabilities, fewer spikes per discharge, and longer initial spike latencies following electrical shocks to the paws. All neurons except one were sensitive to hair and/or tap stimulation, and about two-thirds responded to visual and/or auditory input as well. The neurons had wide, bilateral cutaneous receptive fields, and no evidence for somatotopic organization was found within the cortical tissue sampled. To describe the population response patterns of them neurons, time-depth spike density surfaces were constructed for each input. All the response patterns following electrical stimulation of each paw showed peaks of activity within layer V; the patterns differed mainly in the absolute timing of the discharge. As in fields 4γ and 3b, maximumm neuron activity was roughly correlated in time with the surface-positive phases of the concomitant cortical evoked potentials. In contrast to fields 4γ and 3b, no clear modulatory influences onm neurons from neighboring cortical neuronal subsets were detected following cutaneous stimulation. The present data are consistent with the view that ‘continuous’ gradients of neuronal subsets extend through different cytoarchitectonic fields of motorsensory cortex, with wide-field neurons predominating anteriorly and small-field neurons, posteriorly.

Response properties of mechanosensitive nerve fibers innervating cephalic skin of the texas rat snake.

Abstract The response properties of 146 single maxillary nerve fibers innervating the cephalic integument of 11 Texas rat snakes were studied. Twenty-one of these fibers (14%) were exclusively activated by mechanical stimulation of specialized cutaneous corpuscles. The remaining 125 fibers (86%) were excited by mechanical deformation of skin surrounding, but not including, the specialized corpuscles; these “noncorpuscle units” were placed into three classes on the basis of adaptation rate. (i) Sixty-eight percent of the fibers were rapidly adapting units, discharging only during the moving phase of skin deformation. All rapidly adapting units gave “on” responses, and 46% also gave “off” responses; 72% of these units were able to faithfully discharge one impulse during each cycle of a 256-Hz vibratory stimulus. The rapidly adapting units had the highest stimulus thresholds ( X = 590.6 mg ) and the smallest receptive fields ( X = 12.0 mm 2 ). (ii) Twenty-six percent of the fibers were slowly adapting units, discharging during both the dynamic and static phases of skin deflection. All slowly adapting units gave “on” responses, but only 22% gave “off” responses; 31% of the units were able to respond faithfully during each cycle of vibratory stimulation at a frequency of 256 Hz. The slowly adapting units had the lowest stimulus thresholds ( X = 453.0 mg ) and the largest receptive fields ( X = 18.3 mm 2 ). (iii) Six percent of the fibers had adaptation rates and other response properties intermediate between those of the other two fiber types, and were classified as intermediately adapting units. The receptive fields of most noncorpuscle fibers within each class were relatively small, and were confined to one or two supralabial scales.