Student elective USA, November 1992-January 1993.
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Biomedical subjects
Publications and source records attributed to A R Gibson.
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Somatosensory responses of cells in the dorsal accessory olive are suppressed following stimulation of the magnocellular red nucleus. Since the magnocellular red nucleus of the cat does not project directly to the dorsal accessory olive, the present experiments were designed to identify indirect pathways that might mediate suppression of olivary responsiveness. Wheat germ agglutinin-horseradish peroxidase was used to compare the location of magnocellular red nucleus terminals with the locations of cells providing input to the rostral dorsal accessory olive. Cells projecting to forelimb rostral dorsal accessory olive can be divided into two main groups: one group comprises a column of large cells located in the ventral caudal cuneate nucleus extending into lamina VI of C1 and C2, and a second group comprises smaller cells located in the ventral rostral cuneate nucleus. Terminations of fibers originating in the magnocellular red nucleus were found to target both groups of cells projecting to the dorsal accessory olive. Therefore, it is possible that the responsiveness of olivary cells is influenced via these terminations. Stimulation of sensorimotor cortex has also been shown to inhibit olivary responsiveness. Terminations from sensorimotor cortex target the same regions of cells that project to the dorsal accessory olive as those of the magnocellular red nucleus, and a similar, perhaps identical, anatomical substrate may serve to modulate olivary sensitivity by the two descending systems.
Cruciate paralysis is a clinical entity in which patients with trauma to the anterior cervicomedullary junction present with weakness of the upper extremity greater than that of the lower extremity. The underlying mechanism of this paralysis is commonly thought to be selective damage affecting the upper-extremity nerve fibers in the pyramidal decussation. The authors examined the anatomical basis of cruciate paralysis in six New World squirrel monkeys and two Old World cynomolgus monkeys. No evidence for a differential decussation of fore-limb and hind-limb fibers was found. Thus, there is no obvious anatomical explanation for cruciate palsy. The results do suggest two alternative explanations for cruciate paralysis: 1) selective damage to neural areas involving the internuncial cells, the central gray area, and the cuneate nucleus, or 2) injury to the ventral corticospinal tract.
1. The sensory responsiveness of cells in the inferior olive is known to be suppressed during certain phases of active movement. These experiments were designed to test the possibility that activity in the rubrospinal pathway contributes to this suppression. We recorded from cells sensitive to light touch located in one of the divisions of the inferior olive, the rostral dorsal accessory olive (rDAO), in cats anesthetized with pentobarbitol sodium. Responsiveness to peripheral stimuli was tested during and after trains of conditioning stimuli delivered to the rubrospinal pathway. 2. All 44 cells in our sample of rDAO neurons showed an inhibition of responsiveness to peripheral stimuli after conditioning stimulation of the rubrospinal pathway. Typical conditioning trains consisted of 0.2-ms pulses at 200 Hz for 100 ms. The mean current required for a reduction in firing probability to 0.5 was 31 microA. Slight increases in intensity often completely inhibited responses to peripheral stimuli. 3. Inhibition of responsiveness showed a delayed time course. Peak inhibition occurred approximately 50 ms after the last pulse in the conditioning train. In many cases there was no demonstrable inhibition during the conditioning train. Increases of train frequency, train duration, or stimulus intensity produced stronger and broader periods of olivary inhibition. 4. The lowest threshold points for eliciting rDAO inhibition coincided with either the magnocellular red nucleus (RNm) or the rubrospinal tract (RST). Stimulation at RST sites produced inhibition of responses in the contralateral but not in the ipsilateral rDAO. Transection of the RST in the upper brain stem blocked the inhibition produced by red-nucleus stimulation without altering the inhibition produced by tract stimulation caudal to the transection. The inhibitory effects thus appear to be caused by activation of the rubrospinal pathway. 5. The inhibitory timing observed in this study may be appropriate for explaining the suppression of olivary responsiveness to contact that has been observed in awake animals. Bursts of movement-related, red nucleus discharge often cease approximately 50 ms before the end of movement. This timing would allow peak inhibition to develop at approximately the time of contact with an object at the end of a goal-directed limb movement.
Classical studies of the cat rubrospinal tract describe dense terminations in spinal laminae V-VII and an absence of any significant projection to lamina IX. In contrast, our recent studies, utilizing the anterograde transport of wheat germ agglutinin conjugated with horseradish peroxidase, have demonstrated a consistent and circumscribed area of label in lamina IX at caudal cervical segments. The present study was undertaken to determine the distribution of rubrospinal terminals among motor neurons in lamina IX as well as to identify the likely target muscles of those motor neurons located near rubrospinal terminals. We injected wheat germ agglutinin-horseradish peroxidase into the red nucleus and unconjugated horseradish peroxidase into selected forearm muscles of the same side of the body. The locations of rubrospinal terminals showing anterograde label on one side of the spinal cord could then be compared with the locations of motor neurons showing retrograde label on the opposite side of the cord. The results demonstrated a clear focus of rubrospinal terminals in the lateral and dorsal portions of the ventral horn beginning at C8 and extending through rostral T1. No other segments of the spinal cord showed a focus of rubrospinal terminations in lamina IX. Retrogradely labeled motor neurons from the muscle injections showed that the rubrospinal terminals overlap extensively with motor neuronal pools supplying distal forearm muscles. Several lines of evidence indicate that the terminals are from rubrospinal fibers and are not due to transneuronal transport.
The rostral dorsal accessory olive (rDAO) contains a detailed somatosensory map of the entire contralateral body surface. The rDAO projects to the anterior interpositus nucleus (NIA) directly as well as indirectly by way of Purkinje cells in cerebellar cortex. NIA maintains a topographic relation to different levels of the spinal cord through a relay in the magnocellular red nucleus (RNm) and, thus, contains a motor somatotopy. By using bidirectional transport of WGA-HRP, we demonstrate that the sensory somatotopy of rDAO aligns with the motor somatotopy of NIA. It is likely that rDAO information supplied to the cerebellum from a specific part of the body is used to influence movements restricted to that same body part.
Afferent and efferent connections of the limb specific divisions of the cat magnocellular red nucleus (RNm) were traced using the bidirectional transport of wheatgerm agglutinin-horseradish peroxidase complex (WGA-HRP). Injection sites within forelimb or hindlimb RNm regions were identified by microelectrode recording and confirmed by the position of labeled rubrospinal terminals. Additional injections into structures that project to, or receive input from, RNm confirmed the somatotopic organization of these pathways. The forelimb region of RNm receives input from the posteriolateral part of the anterior interpositus nucleus (NIA) and the intermediate part of the posterior interpositus nucleus (NIP). The hindlimb region of RNm receives input from anteriomedial NIA and medial NIP. Terminals of NIA cells densely fill all of RNm, but terminals of NIP cells form a half shell on the medial, ventral, and posterior borders of RNm without encroaching on RNm's lateral edge or central core. Forelimb and hindlimb RNm are reciprocally connected with the caudal cuneate and gracile nuclei respectively. There is little or no input to RNm from the medial or lateral cerebellar nuclei. Forelimb RNm, which also contains a face representation, projects to the lateral reticular nucleus, cell group f of the inferior vestibular nucleus, the facial nucleus, the main sensory nucleus of the trigeminal nerve, the caudal cuneate nucleus, the parvicellular reticular formation, and cervical segments of the spinal cord. A few fibers from forelimb RNm project directly to motor neurons in the lower cervical cord. Hindlimb RNm projects to only the lateral reticular nucleus, gracile nucleus, and lower spinal segments. Forelimb and hindlimb RNm project to different regions of the lateral reticular nucleus with some overlap.
Single unit recording in awake monkeys was used to search for functional differences between the two divisions of the red nucleus, and anatomical tracing of WGA-HRP was used to investigate inputs to the two divisions. We studied a total of 323 units in 4 red nuclei of two monkeys. Recording sites were identified in histological sections by the locations of lesions and the reconstruction of electrode tracks. Of the units in the RNm 98.5% discharged in high frequency bursts during movement. Only 52% showed reliable responses to somatosensory stimulation, and the responses observed were weaker than the movement-related discharge. None of the units recorded in the RNp showed strong movement-related discharge, and 51% were completely unresponsive during both motor and sensory tests. A dorsolateral group of medium-sized cells that overlaps the rostral half of the main RNm and the caudal pole of RNp appears to represent an extension of the magnocellular region. Retrograde transport of WGA-HRP indicated that some of these cells are rubrospinal neurons. Furthermore, the discharge properties of dorsolateral neurons are like the main RNm neurons, except for lower discharge rates and smaller spike amplitudes. Mouth movements are strongly represented in the dorsolateral region. Anterograde transport of WGA-HRP from the motor cortex demonstrated dense terminal label in RNp as contrasted with light label in RNm. Retrograde transport of WGA-HRP from RNm labeled many more cells in the cerebellar interpositus nucleus than in motor cortex. We concluded that input to RNm from the cerebellum is the likely source of the strong movement-related activity recorded from cells in the RNm. The absence of appreciable movement-related activity in parvicellular red nucleus provides a clear functional distinction between this division and the magnocellular division of the red nucleus.
Three hundred and thirty-four neurones located in the magnocellular division of red nucleus (r.n.m.) were studied in three alert macaque monkeys. These cells had low discharge rates at rest and produced high frequency bursts during movement. Single cells were selectively active for movement of one body part, and a motor somatotopy was evident. From dorsal to ventral we encountered cells related to movements of the face, contralateral upper limb, contralateral lower limb and, in one case, the tail. Free-form tests indicated that 76% of upper-limb cells were preferentially related to hand and finger movements, and 84% of lower limb cells were preferentially related to foot and toe movements. Quantitative tests of movement relations were based on depths of modulation in discharge rate recorded while the monkeys operated several devices that served as manipulanda in a tracking task; each device elicited a different movement. We conducted 220 tests on eighty-one cells using eleven devices. The modulation in discharge rate exceeded a 50 pulses/s criterion level in seventy-nine cases; eleven were well related to proximal movements, twenty-two to movements of the digits and forty-six to a co-ordinated hand movement elicited by a device called the twister. Both unidirectional and bidirectional patterns of bursting were frequent. A few cells showed reciprocal patterns consisting of a large increase in rate for one direction of movement and a small decrease for the other. The bursts in discharge preceded movement onset (97% of 132 cases) by an average of 135 ms. Electromyographic activity in forearm muscles preceded movement by about 55 ms. In some cases we recorded from a single cell while the monkey operated two, three or four devices. Depth of modulation on the twister device was twice that on a proximal device in nine cases whereas one case showed a proximal device preference; five cases showed overlap. Comparison between twister and digits yielded ten cases of twister preference, four of digit preference and twenty cases of overlap. A directional preference was found for ten out of eleven cells responsive during active movement restricted to the metacarpo-phalangeal joints, and in all cases the preferred direction was extension. Responses to natural somatosensory stimulation were weak or absent for the majority of cells. When present, sensory fields were confined to the same limb but were frequently out of register with motor fields.(ABSTRACT TRUNCATED AT 400 WORDS)
Correlation and regression analyses were performed on thirty-three of the magnocellular red nucleus cells described in the previous paper. We sought to test for reliable relations between the parameters of individual tracking movements and corresponding bursts of neural discharge. High correlations were found between the following burst and movement parameters: (i) burst latency versus movement latency; (ii) burst duration versus movement duration; (iii) burst frequency versus movement velocity and (iv) number of spikes in the burst versus movement amplitude. Cells were ranked according to the average of the duration, velocity and amplitude correlation coefficients. The top twenty cells had average correlation coefficients ranging from 0.69 to 0.88 for their preferred movement. These cases were judged most likely to reveal the control functions of the red nucleus, and the following points refer to this sample. Burst onset led movement onset by 118 +/- 23 ms, and burst offset led movement offset by 50 +/- 38 ms. Burst duration increased as the duration of the movement increased (r = 0.87 +/- 0.11). The duration of the burst was approximately equal to movement duration (slope of 0.99 +/- 0.16) plus a constant (72 +/- 34 ms) throughout a broad range. Average discharge rate during the burst increased with average movement velocity (r = 0.69 +/- 0.15). The slope of the relation was 0.36 +/- 0.21 (pulses/s)/(deg/s) of joint rotation. The regression lines had consistent upward offsets (56 +/- 15 pulses/s) that exceeded the spontaneous discharge rate (17 +/- 10 pulses/s). The number of spikes in the burst increased with movement amplitude independent of velocity (r = 0.72 +/- 0.11). The slope of the relation was 0.62 spikes/deg and the offset was 13 +/- 4 spikes. The preferred movement was co-ordinated hand in fifteen cases, digit in three, elbow in one and shoulder in one. When these cells were tested with an alternate movement, the failure rate (cases in which a burst did not accompany a movement) increased from 1.4 to 20%, and the correlation coefficients generally were low and lacked significance. Cells in the top twenty had directionally specific responses, low variance in lead time, large depths of modulation (41-118 pulses/s) and low failure rates. Cells that failed to show strong parametric correlations often had one or more of the former attributes. It appears that high parametric correlations with individual movements are particularly restrictive criteria of relatedness.(ABSTRACT TRUNCATED AT 400 WORDS)
We have recorded from 306 neurons in the inferior olive of six alert cats. Most of the cats were trained to perform a simple task with the forelimb. We observed the neural responses to a wide variety of cutaneous and proprioceptive stimuli, as well as responses during spontaneous and learned active movements. Neurons responsive to somatosensory stimulation were found in all parts of the inferior olive, and they were roughly evenly divided between those responsive to cutaneous stimulation and those responsive to proprioceptive stimulation. In the dorsal accessory olive all neurons were responsive to somatosensory stimulation. In the medial accessory nucleus 88% and in the principal olive 74% of cells were responsive to somatosensory stimulation. Cells responsive to cutaneous stimulation usually had small receptive fields, commonly on the paw. These cells had low-threshold responses to one or more forms of cutaneous stimulation and typically fired one spike at the onset of the stimulus on 80% or more of stimulus applications. Cells responsive to proprioceptive stimulation most commonly responded to passive displacements of a limb. These cells were often very sensitive, responding to linear displacements of less than 1 cm in one specific direction. No cells in our sample responded reliably during active movement by the animal. Only 21% of cells responding to passive proprioceptive stimulation showed any modulation during active movement, and the modulation was weak. Likewise, cells responsive to cutaneous stimulation generally failed to respond when a similar stimulus was produced by an active movement by the animal. Exceptions to this were stimuli produced during exploratory movements or when the receptive field unexpectedly made contact with an object during active movement. Electrical stimulation applied in the inferior olive failed to evoke movements or to modify ongoing movement. Our results are consistent with the hypothesis that inferior olivary neurons function as somatic event detectors responding particularly reliably to unexpected stimuli.
A TMB reaction with increased sensitivity and lower artifact can be obtained by dividing the Mesulam reaction into two stages. Use of the modified reaction with HRP conjugated wheat germ agglutinin (WGA-HRP) yields a powerful technique for anterograde and retrograde tracing.
The occurrence of pustular folliculitis in eight people after the use of health-spa whirlpools is described for the first time in Australia. The lesions were discovered ad identified during the peak season in two resorts in the Snowy Mountains area near Jindabyne, New South Wales. Pseudomonas aeruginosa, identified as serotype 0:6, was isolated from pus swabs of the lesions, water in the spa pools and pool filters.
We examined the somatosensory properties of 391 neurons in the inferior olive in 20 cats that were anesthetized with barbiturate or decerebrated. A response consisted of a single spike with a variable number of wavelets followed by a long refractory period. Neurons responsive to natural somatosensory stimuli were recorded in all olivary subdivisions. The dorsal accessory olive (DAO) contained the highest proportion of responsive units (96%), compared with 66% for the medial accessory olive (MAO) and 43% for the principal olivary (PO) nucleus. Within the rostral DAO we found a refined cutaneous map of the entire contralateral body surface. In the caudal DAO responsiveness to manipulation of deep tissues became prominent, and both individual limbs and bilateral pairs were represented. In the medial region of the PO responsiveness to taps predominated and bilaterally symmetrical fields were frequent. The lateral PO was unresponsive under the conditions of these experiments. The MAO was distinguished by a greater complexity of receptive field and by a preponderance of deep over cutaneous modality. The lateral part of caudal MAO contained cells with interesting spatial patterns of excitation and inhibition, whereas most cells in the rostral MAO had purely excitatory fields. A teleceptive area receiving visual and auditory input was recognized in the medial MAO and nearby structures such as the dorsal cap. Contact and proprioceptive signals arriving via climbing fibers may provide the cerebellum with information necessary to relate the body to external objects.
Neural activity of the red nucleus was studied in monkeys trained to operate devices requiring shoulder, elbow, wrist, hand, or finger movements. Single cell activity was more closely related to movements of the hand and fingers than to movements of the other joints. Discharge consistently preceded movements by a constant time interval; duration of discharge was highly correlated with the duration of movement; and discharge rate was highly correlated with movement velocity. These data suggest a role for the rubrospinal pathway in the initiation and control of hand movements.
Exclusion diets may have a practical place in determining the precipitating dietary factors in certain clinical conditions. We present an exclusion diet which is based on the exclusion of food commonly known to cause food allergies, and the exclusion of food which contains salicylates, benzoates, tartrazine, yeast, and penicillin. This provided a basis for challenge with these additives and natural chemicals. Preliminary information in urticaria suggests a use for this diet in some allergic conditions.
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