Effect of a polymorphism in the ND1 mitochondrial gene on human skeletal muscle mitochondrial function.

OBJECTIVE: A non-silent polymorphism in the mitochondrial coding region of the ND1 gene, a subunit of reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase is associated with resting metabolic rate (RMR) in 245 non-diabetic Pima Indians. The purpose of this investigation was to determine the effect of the ND1 gene polymorphism on mitochondrial function in 14 male Pima Indians. METHODS AND PROCEDURES: Seven subjects with an A at site 3547 of the ND1 gene (Ile at amino acid 81), and seven with a G at this site (Val) were studied. Mitochondria were isolated from 0.8 to 1.5 g of skeletal muscle obtained by needle biopsy of the lateral quadriceps muscle. In intact mitochondria, maximal (state-3) and resting (state-4) respiration rates were measured polarographically at 37 degrees C with a variety of single substrates or substrate combinations. Disrupted mitochondria were analyzed for maximal capacities through the entire electron transport chain (ETC) (NADH oxidase (NADHOX)), as well as through a segment of Complex I that is independent of the ND1 component (NADH-ferricyanide (NADH-FeCN) reductase). RESULTS: Mitochondria were well coupled and exhibited higher respiratory control ratios (RCRs) than rodent muscle. There were no differences between the two groups for any of the measured parameters. DISCUSSION: These results indicate that the cause of the observed association between RMR and the ND1 polymorphism is not related to in vitro mitochondrial function.

Processing of vibrotactile inputs from hairy skin by neurons of the dorsal column nuclei in the cat.

The capacity of single neurons of the dorsal column nuclei (DCN) for coding vibrotactile information from the hairy skin has been investigated in anesthetized cats to permit quantitative comparison first with the capacities of DCN neurons responding to glabrous skin vibrotactile inputs and second with those of spinocervical tract neurons responding to vibrotactile inputs from hairy skin. Dynamically sensitive tactile neurons of the DCN the input of which came from hairy skin could be divided into two classes, one associated with hair follicle afferent (HFA) input, the other with Pacinian corpuscle (PC) input. The HFA-related class was most sensitive to low-frequency (<50 Hz) vibration and had a graded response output as a function of vibrotactile intensity changes. PC-related neurons had a broader vibrotactile sensitivity, extending to > or =300 Hz and appeared to derive their input from the margins of hairy skin, near the footpads, or from deeper PC sources such as the interosseous membranes or joints. HFA-related neurons had phaselocked responses to vibration frequencies up to approximately 75 Hz, whereas PC neurons retained this capacity up to frequencies of approximately 300 Hz with tightest phaselocking between 50 and 200 Hz. Quantitative measures of phaselocking revealed that the HFA-related neurons provide the better signal of vibrotactile frequency up to approximately 50 Hz with a switch-over to the PC-related neurons above that value. In conclusion, the functional capacities of these two classes of cuneate neuron appear to account for behavioral vibrotactile frequency discriminative performance in hairy skin, in contrast to the limited capacities of vibrotactile-sensitive neurons within the spinocervical tract system.

Vibrotactile coding capacities of spinocervical tract neurons in the cat.

The response characteristics and tactile coding capacities of individual dorsal horn neurons, in particular, those of the spinocervical tract (SCT), have been examined in the anesthetized cat. Twenty one of 38 neurons studied were confirmed SCT neurons based on antidromic activation procedures. All had tactile receptive fields on the hairy skin of the hindlimb. Most (29/38) could also be activated transynaptically by electrical stimulation of the cervical dorsal columns, suggesting that a common set of tactile primary afferent fibers may provide the input for both the dorsal column-lemniscal pathway and for parallel ascending pathways, such as the SCT. All but 3 of the 38 neurons studied displayed a pure dynamic sensitivity to controlled tactile stimuli but were unable to sustain their responsiveness throughout 1s trains of vibration at vibration frequencies exceeding 5-10 Hz. Stimulus-response relations revealed a very limited capacity of individual SCT neurons to signal, in a graded way, the intensity parameter of the vibrotactile stimulus. Furthermore, because of their inability to respond on a cycle-by-cycle pattern at vibration frequencies >5-10 Hz, these neurons were unable to provide any useful signal of vibration frequency beyond the very narrow bandwidth of approximately 5-10 Hz. Similar limitations were observed in the responsiveness of these neurons to repetitive forms of antidromic and transynaptic inputs generated by electrical stimulation of the spinal cord. In summary, the observed limitations on the vibrotactile bandwidth of SCT neurons and on the precision and fidelity of their temporal signaling, suggest that SCT neurons could serve as little more than coarse event detectors in tactile sensibility, in contrast to DCN neurons the bandwidth of vibrotactile responsiveness of which may extend beyond 400 Hz and is therefore broader by approximately 40-50 times than that of SCT neurons.

Vibrotactile frequency discrimination in human hairy skin.

The human capacity for vibrotactile frequency discrimination has been compared directly for glabrous and hairy skin regions by means of a two-alternative, forced-choice psychophysical procedure in five subjects. Sinusoidal vibratory stimuli, delivered by means of a 4-mm-diam probe, were first used to obtain detection threshold values for the two skin sites, the finger tip and the dorsal forearm, at four standard frequencies, 20, 50, 100, and 200 Hz. Values confirmed previous results showing detection thresholds were markedly higher on hairy skin than on glabrous skin. For the discrimination task, each standard frequency, at an amplitude four times detection threshold, was paired with a series of comparison frequencies, and discrimination capacity then was quantified by deriving from psychometric function curves, measures of the discriminable frequency increment (Deltaf) and the Weber Fraction (Deltaf/f), which, when plotted as a function of the four standard frequencies, revealed similar capacities for frequency discrimination at the two skin sites at the standard frequencies of 20, 100, and 200 Hz but an equivocal difference at 50 Hz. Cutaneous local anesthesia produced a marked impairment in vibrotactile detection and discrimination at the low standard frequencies of 20 and 50 Hz but little effect at higher frequencies. In summary, the results reveal, first, a striking similarity in vibrotactile discriminative performance in hairy and glabrous skin despite marked differences in detection thresholds for the two sites, and, second, the results confirm that vibrotactile detection and discrimination in hairy skin depend on superficial receptors at low frequencies but depend on deep, probably Pacinian corpuscle, receptors for high frequencies.

Mechanosensory perception: are there contributions from bone-associated receptors?

1. The identity of the receptors and afferent nerve fibres that mediate the sense of touch varies somewhat with body location. Those that have been most intensively characterized are associated with the distal glabrous skin of the limbs and, in primates, mediate the sense of touch in the fingertips and palms. In this glabrous skin region, there appear to be three or four principal classes of tactile sensory nerves that fall into two broad groups. One group, the so-called slowly adapting (SA) receptors and afferent fibres, is responsive to static mechanical displacement of skin tissues and is made up of two classes, the type I (SAI) fibres that innervate Merkel receptors and the type II (SAII) fibres that innervate Ruffini endings. The second broad group displays a pure dynamic sensitivity to tactile stimuli and also falls into two principal classes, the rapidly adapting (RA) tactile fibres that are associated with Meissner corpuscle receptors and the Pacinian corpuscle (PC)-associated class of tactile afferent fibres. 2. In other regions of the skin, such as the hairy skin of the arms, legs and trunk, there are similar functional classes of tactile sensory nerves, although the receptor endings differ somewhat from those of the glabrous skin. 3. Receptors in close association with the long bones of the limbs include groups of Pacinian corpuscles distributed along the interosseous membranes. These are highly sensitive to dynamic forms of mechanical stimuli, in particular vibrotactile disturbances. However, despite their close association with bone, these receptors probably cannot be legitimately considered 'osseoreceptors'. 4. Both the periosteum and the bone marrow are richly supplied by nerve fibres. However, much evidence indicates that these are largely or entirely in the fine-diameter category of nerve fibres, whose roles may be confined to either nociception or to the efferent autonomic regulation of bone-associated blood vessels. 5. In conclusion, it remains uncertain whether any aspects of our innocuous touch or kinaesthetic senses, in either the limbs or in orofacial regions, can be ascribed to 'osseoreceptors' located in the periosteum or within the bone marrow itself.

Tactile neural mechanisms in monotremes.

Monotremes, perhaps more than any other order of mammals, display an enormous behavioural reliance upon the tactile senses. In the platypus, Ornithorhynchus anatinus, this is manifest most strikingly in the special importance of the bill as a peripheral sensory organ, an importance confirmed by electrophysiological mapping that reveals a vast area of the cerebral cortex allocated to the processing of tactile inputs from the bill. Although behavioural evidence in the echidna, Tachyglossus aculeatus, suggests a similar prominence for tactile inputs from the snout, there is also a great reliance upon the distal limbs for digging and burrowing activity, pointing to the importance of tactile information from these regions for the echidna. In recent studies, we have investigated the peripheral tactile neural mechanisms in the forepaw of the echidna to establish the extent of correspondence or divergence that has emerged over the widely different evolutionary paths taken by monotreme and placental mammals. Electrophysiological recordings were made from single tactile sensory nerve fibres isolated in fine strands of the median or ulnar nerves of the forearm. Controlled tactile stimuli applied to the forepaw glabrous skin permitted an initial classification of tactile sensory fibres into two broad divisions, according to their responses to static skin displacement. One displayed slowly adapting (SA) response properties, while the other showed a selective sensitivity to the dynamic components of the skin displacement. These purely dynamically-sensitive tactile fibres could be subdivided according to vibrotactile sensitivity and receptive field characteristics into a rapidly adapting (RA) class, sensitive to low frequency (

Impulse propagation over tactile and kinaesthetic sensory axons to central target neurones of the cuneate nucleus in cat.

Paired, simultaneous recordings were made in anaesthetized cats from the peripheral and central axons of individual tactile and kinaesthetic sensory fibres. The aim was to determine whether failure of spike propagation occurred at any of the three major axonal branch points in the path to their cuneate target neurones, and whether propagation failure may contribute, along with synaptic transmission failures, to limitations in transmission security observed for the cuneate synaptic relay. No evidence for propagation failure was found at the two major axonal branch points prior to the cuneate nucleus, namely, the T-junction at the dorsal root ganglion, and the major branch point near the cord entry point, even for the highest impulse rates (approximately 400 impulses s(-1)) at which these fibres could be driven. However, at the highest impulse rates there was evidence at the central, intra-cuneate recording site of switching between two states in the terminal axonal spike configuration. This appears to reflect a sporadic propagation failure into one of the terminal branches of the sensory axon. In conclusion, it appears that central impulse propagation over group II sensory axons occurs with complete security through branch points within the dorsal root ganglion and at the spinal cord entry zone. However, at high rates of afferent drive, terminal axonal propagation failure may contribute to the observed decline in transmission security within the cuneate synaptic relay.

Transmission security for single, hair follicle-related tactile afferent fibers and their target cuneate neurons in cat.

Transmission from single, identified hair follicle afferent (HFA) nerve fibers to their target neurons of the cuneate nucleus was examined in anesthetized cats by means of paired recording from individual cuneate neurons and from fine, intact fascicles of the lateral branch of the superficial radial nerve in which it is possible to identify and monitor the activity of each group II fiber. Selective activation of individual HFA fibers was achieved by means of focal vibrotactile skin stimulation. Forearm denervation precluded inputs from sources other than the monitored HFA sensory fiber. Transmission characteristics were analyzed for 21 HFA fiber-cuneate neuron pairs in which activity in the single HFA fiber of each pair reliably evoked spike output from the target neuron at a fixed latency. As the cuneate responses to each HFA impulse often consisted of 2 or 3 spikes, in particular at HFA input rates up to approximately 20 imp/s, the synaptic linkage displayed potent amplification and high-gain transmission, characteristics that were confirmed quantitatively in measures of transmission security and cuneate spike output measures. In response to vibrotactile stimuli, the tight phase locking in the responses of single HFA fibers was well retained in the cuneate responses for vibration frequencies up to approximately 200 Hz. On measures of vector strength, the phase locking declined across the synaptic linkage by no more than approximately 10% at frequencies up to 100 Hz. However, limitations on the impulse rates generated in both the HFA fibers their associated cuneate neurons meant that the impulse patterns could not directly signal information about the vibration frequency above 50-100 Hz. Although single HFA fibers are also known to have secure synaptic linkages with spinocervical tract neurons, it is probable that this linkage lacks the capacity of the HFA-cuneate synapse for conveying precise temporal information, in an impulse pattern code, about the frequency parameter of vibrotactile stimuli.

Characterization of tactile afferent fibers in the hand of the marmoset monkey.

The marmoset monkey, Callithrix jacchus, has increasingly been the subject of experiments for the analysis of somatosensory system function in simian primates. However, as response properties of the mechanoreceptive afferent fibers supplying the skin have not been characterized for this primate, the present study was undertaken to classify fibers innervating the glabrous skin of the marmoset hand and determine whether they resembled those described for other mammalian species, including cat, macaque monkey, and human subjects. Forty-seven tactile afferent fibers with receptive fields (RFs) on the glabrous skin of the hand were isolated in fine median and ulnar nerve strands. Controlled tactile stimuli, including static indentation and skin vibration, were used to classify fibers. Twenty-six (55%) responded to static indentation in a sustained manner and were designated slowly adapting (SA) fibers, while 21 (45%) were selectively sensitive to the dynamic components of the stimulus. The SA fibers had well-defined boundaries to their RFs, lacked spontaneous activity in most cases (23/26 fibers), had an irregular pattern of discharge to static skin indentation, and displayed graded response levels as a function of indentation amplitude, attributes that were consistent with the properties of slowly adapting type I (SAI) fibers described in other species. The dynamically sensitive afferent fibers could be subdivided into two distinct functional classes, based on their responses to vibrotactile stimulation. The majority (15/21) responded best to lower frequency vibration (~10-50 Hz) and had small RFs, whereas the second class responded preferentially to higher frequency vibration (50-700 Hz) with maximal sensitivity at ~200-300 Hz. These two classes resembled, respectively, the rapidly adapting (RA) and Pacinian corpuscle-related (PC) fiber classes found in other species, and like them, responded to vibration with tightly phase-locked patterns of response over a wide range of frequencies. The results demonstrate that the functional classes of tactile afferent fibers that supply the glabrous skin in the marmoset monkey appear to correspond with those described previously for the cat and macaque monkey, and are similar to those supplying the human hand and fingers, although the SA fibers in the human hand appear to fall into two classes, the SAI and SAII fibers. With the increasing use of the marmoset monkey as a primate model for somatosensory system studies, these data now allow tactile neurons identified at central locations, such as the cerebral cortex and thalamus, to be classified in relation to inputs from the peripheral classes identified in the present study.

Functional characteristics of the parallel SI- and SII-projecting neurons of the thalamic ventral posterior nucleus in the marmoset.

The functional organization of the primate somatosensory system at thalamocortical levels has been a matter of controversy, in particular, over the extent to which the primary and secondary somatosensory cortical areas, SI and SII, are organized in parallel or serial neural networks for the processing of tactile information. This issue was investigated for the marmoset monkey by recording from 55 single tactile-sensitive neurons in the lateral division of the ventral posterior nucleus of the thalamus (VPL) with a projection to either SI or SII, identified with the use of the antidromic collision technique. Neurons activated from the hand and distal forearm were classified according to their peripheral source of input and characterized in terms of their functional capacities to determine whether the direct thalamic input can account for tactile processing in both SI and SII. Both the SI- and SII-projecting samples contained a slowly adapting (SA) class of neurons, sensitive to static skin displacement, and purely dynamically sensitive tactile neurons that could be subdivided into two classes. One was most sensitive to high-frequency (> or =100 Hz) cutaneous vibration whose input appeared to be derived from Pacinian sources, while the other was sensitive to lower frequency vibration (< or =100 Hz) or trains of rectangular mechanical pulse stimuli, that appeared to receive its input from rapidly adapting (RA) afferent fibers presumed to be associated with intradermal tactile receptors. There appeared to be no systematic differences in functional capacities between SI- and SII-projecting neurons of each of these three classes, based on receptive field characteristics, on the form of stimulus-response relations, and on measures derived from these relations. These measures included threshold and responsiveness values, bandwidths of vibrational sensitivity, and the capacity for responding to cutaneous vibrotactile stimuli with phase-locked, temporally patterned impulse activity. The analysis indicates that low-threshold, high-acuity tactile information is conveyed directly to both SI and SII from overlapping regions within the thalamic VP nucleus. This direct confirmation of a parallel functional projection to both SI and SII in the marmoset is consistent with our separate studies at the cortical level that demonstrate first, that tactile responsiveness in SII largely survives the SI inactivation and second, that SI responsiveness is largely independent of SII. It therefore reinforces the evidence that SI and SII occupy a hierarchically equivalent network for tactile processing.

Hierarchical equivalence of somatosensory areas I and II for tactile processing in the cerebral cortex of the marmoset monkey.

Responsiveness of the first somatosensory area (SI) of the cerebral cortex was investigated in the marmoset monkey (Callithrix jacchus) in association with cooling-induced, reversible inactivation of the second somatosensory area, SII. The aim was to determine whether SI responsiveness to peripheral tactile stimulation depends on SII and therefore whether SI and SII in the marmoset occupy hierarchically equivalent positions in a parallel organizational scheme for thalamocortical tactile processing as appears to be the case in nonprimate mammals. Inactivation of SII was achieved when the temperature over SII was lowered to < or =12 degrees C, as indicated by abolition of the SII-evoked potentials generated by brief tap stimuli to the hand or foot, and by abolition of tactile responses in single SII neurons located at the margin beneath the block. The effect of SII inactivation on SI-evoked potentials was examined in 16 experiments by simultaneous recording of the SI- and SII-evoked potentials. SI-evoked potentials were never abolished and remained unaffected in 11 cases. In three experiments there was a small reduction in amplitude and inconsistent effects in the remaining two. Responsiveness to controlled tactile stimuli was examined quantitatively in 31 individual SI neurons of different functional classes before, during, and after the inactivation of SII. Tactile responsiveness in individual SI neurons was never abolished by SII inactivation, remaining unchanged in 20 neurons (65%) while undergoing some reduction in the remaining 11 SI neurons (35%). This reduction of tactile responsiveness in one-third of SI neurons is most likely attributable to a removal of a facilitatory influence emanating from SII, based on the observation that background activity of the affected neurons was also reduced. Furthermore, phase locking of SI responses to vibrotactile stimulation was unchanged when SII was inactivated. The retention of responsiveness in SI neurons when SII was inactivated by cooling in the marmoset demonstrates that tactile inputs can reach SI without traversing an indirect, serially organized path through SII. The present results, together with our previous observations that responsiveness in the majority of SII neurons survived SI inactivation, demonstrate that there is a parallel organization of the SI and SII areas for tactile processing in the marmoset monkey and that SI and SII occupy hierarchically equivalent positions in a parallel processing network. There is therefore no longer justification for the view that there are fundamental differences in the organization of thalamocortical tactile processing for SI and SII between simian primates, in general, and other mammals.

Haplogroup-associated differences in neonatal death and incidence of low birth weight at elevation: a preliminary assessment.

OBJECTIVE: We sought to assess reproductive fitness differences between mitochondrial deoxyribonucleic acid haplogroups at high altitude. STUDY DESIGN: This study considers differences in outcomes of conception, birth weight, and neonatal mortality rates for 62 women classified according to haplogroups (B or non-B). RESULTS: The number of low-weight births (<2500 g) for the non-B group was significant (P =.019). Mothers in the non-B group reported more spontaneous abortions (P =.171) and stillbirths (P =.301). The difference in conceptions per woman between groups was significant (P =.036). However, no difference in infants alive at 1 month of age was evident. Neonatal death was significant (P =.017). The odds of an unsuccessful outcome among mothers in the B group was compared with mothers in the non-B group and was significant (P =.029). The chance of an adverse outcome, that is, fetal or infant death before 1 month, for mothers in the B group was between 11.1% and 88.7% lower than for mothers in the non-B group. CONCLUSIONS: The neonatal mortality rate for the non-B group was significantly elevated relative to the B group. The molecular basis for these observations is not clear.

Bidirectional communication of sensory afferent information in a peripheral nerve of the cat forelimb.

Kinaesthetic information is derived from both muscle and joint nerves. However, the segregation, at peripheral levels, of inputs from these sources is by no means clear cut. In the present report, we demonstrate the complexity of peripheral innervation of joint and muscle structures in the cat's forearm, in particular, with evidence for bidirectional signalling for different classes of kinaesthetic afferents within a peripheral nerve segment. Three-way simultaneous recordings were carried out in the anaesthetized cat from single kinaesthetic afferents in three nerves that were freed from nearby tissue in the distal forearm, but remained in continuity. These were the wrist-joint nerve and two components of the indicis proprius nerve, one that projects proximally from the muscle to join the deep radial nerve, the other a distal extension of this nerve that runs through and beyond its own muscle to the region of the wrist-joint capsule where it forms an anastomosis with the wrist-joint nerve. Single-unit recording from the intact nerves demonstrated that some spindle afferent fibres from the indicis proprius muscle may take an "ectopic" path to the central nervous system, conveying their signals over an initial centrifugal path via the distal extension of the indicis proprius nerve, before looping back to project centripetally via the "classic" wrist-joint nerve. As some wrist-joint afferents themselves may project "ectopically" via the distal and then proximal segment of the indicis proprius nerve (rather than via the wrist-joint nerve), the recordings demonstrate that, within the distal segment of the indicis proprius nerve, there is bidirectional traffic of kinaesthetic afferent signals, with wrist-joint impulses travelling centripetally and muscle afferent signals travelling centrifugally. The findings emphasize the complexity of signalling that may be present in sensory nerves, on account of the "ectopic" paths taken by some afferents, and the need to activate deep inputs of joint or muscle origin by natural stimulation of the appropriate receptors in order to examine selectively the central actions and processing of either source of input.

Signalling of static and dynamic features of muscle spindle input by external cuneate neurones in the cat.

1. The present experiments examined the capacity of external cuneate nucleus (ECN) neurones in the anaesthetized cat to respond to static and vibrotactile stretch of forearm extensor muscles. The aim was to compare their signalling capacities with the known properties of main cuneate neurones in order to determine whether there is differential processing of muscle spindle inputs at these parallel relay sites. 2. Static stretch (<= 2 mm in amplitude) and sinusoidal vibration were applied longitudinally to individual muscle tendons and responses recorded from single ECN neurones. The muscle-related ECN neurones that were sampled displayed a high sensitivity to both static and dynamic components of stretch, including muscle vibration at frequencies of 50-800 Hz, consistent with their dominant input being derived from primary spindle afferent fibres. 3. In response to ramp-and-hold muscle stretch, ECN neurones resembled their main cuneate counterparts in the pattern of their responses and in quantitative response measures. Their coefficients of variation in interspike intervals during steady stretch ranged from approximately 0.3 to 0.7, as they do in main cuneate responses, and their stimulus-response relations were graded as a function of stretch magnitude with low variability in responses at a fixed stretch amplitude. 4. In response to muscle vibration, ECN activity was tightly phase locked to the vibration waveform, in particular at frequencies of <= 150 Hz, where vector strength measures (R) were high (R >= 0.8) before declining as a function of frequency, with R values of approximately 0.6 at 300 Hz and <= 0.4 at 800 Hz. Both the qualitative and quantitative aspects of ECN responsiveness to the vibro-stretch disturbances were indistinguishable from those of the main cuneate neurones. 5. The results demonstrate a high transmission fidelity for muscle signals across the ECN and no evidence for differential synaptic transmission across the parallel main and external cuneate nuclei. Earlier limitations observed in the capacity of cerebellar Purkinje cells to respond to primary spindle inputs must therefore be imposed at synapses within the cerebellum.

Organization of somatosensory areas I and II in marsupial cerebral cortex: parallel processing in the possum sensory cortex.

Organization of somatosensory areas I and II in marsupial cerebral cortex: parallel processing in the possum sensory cortex. Controversy exists over the organization of mammalian thalamocortical somatosensory networks. An issue of particular contention is whether the primary and secondary somatosensory areas of cortex (SI and SII) are organized in a parallel or serial scheme for processing tactile information. The current experiments were conducted in the anesthetized brush-tail possum (Trichosurus vulpecula) to determine which organizational scheme operates in marsupials, which have taken a quite different evolutionary path from the placental species studied in this respect. The effect of rapid reversible inactivation of SI, achieved by localized cortical cooling, was examined on both evoked potential and single neuron responses in SII. SI inactivation was without effect on the amplitude, latency, and time course of SII-evoked potentials, indicating that the transient inputs responsible for the SII-evoked potential reach SII directly from the thalamus rather than traversing an indirect serial route via SI. Tactile responsiveness was examined quantitatively before, during, and after SI inactivation in 16 SII neurons. Fourteen were unchanged in their responsiveness, and two showed some reduction, an effect probably attributable to the loss of a facilitatory influence exerted by SI on a small proportion of SII neurons. The temporal precision and pattern of SII responses to dynamic forms of mechanical stimuli were unaffected, and temporal dispersion in the SII response bursts was unchanged in association with SI inactivation. In conclusion, the results establish that, within this marsupial species, tactile inputs can reach SII directly from the thalamus and are not dependent on a serially organized path through SI. A predominantly parallel organizational scheme for SI and SII operates in this representative of the marsupial order, as it does in a range of placental mammals including the cat and rabbit, the tree shrew and prosimian galago, and at least one primate representative, the marmoset monkey.

Signalling of static and dynamic features of muscle spindle input by cuneate neurones in the cat.

1. The capacity of cuneate neurones to signal information derived from muscle spindle afferent fibres about static stretch or vibration of forearm extensor muscles was examined electrophysiologically in anaesthetized cats. 2. Static stretch (>= 2 mm in amplitude) and sinusoidal vibration (at frequencies of 50-800 Hz) were applied longitudinally to individual muscle tendons by means of a feedback controlled mechanical stimulator, and responses were recorded from individual cuneate neurones and from individual spindle afferent fibres. 3. Cuneate neurones sampled were located caudal to the obex and displayed a sensitivity to both vibration and static stretch of forearm muscles that was consistent with their input arising from primary spindle endings. In response to static muscle stretch, they displayed graded and approximately linear stimulus-response relations, and a stability of response level at fixed lengths that was consistent with these neurones contributing discriminative information about static muscle stretch. 4. In response to sinusoidal muscle vibration the cuneate neurones also showed graded stimulus-response relations (in contrast to spindle afferents which at low vibration amplitudes attain a plateau response level corresponding to a discharge of 1 impulse on each vibration cycle). Lowest thresholds were at 100-300 Hz and bandwidths of vibration sensitivity extended up to approximately 800 Hz. 5. Temporal precision in cuneate responses to muscle vibration was assessed by constructing phase scatter and cycle histograms from which measures of vector strength could be calculated. Cuneate responses displayed somewhat poorer phase locking (and lower vector strengths) than spindle afferent responses to vibration (a reflection of uncertainties associated with synaptic transmission). Nevertheless, the remarkable feature of cuneate responses to muscle vibration is the preservation of tight phase locking at frequencies up to 400-500 Hz, which presumably enables these central neurones to contribute accurate temporal information for the kinaesthetic sense in a variety of circumstances involving dynamic perturbations to skeletal muscle.

Central projection of proprioceptive information from the wrist joint via a forearm 'muscle' nerve in the cat.

1. Peripheral nerves arising in joint capsules are known to contain a 'contaminating' contribution from muscle afferent fibres. In the present report we provide the first electrophysiological evidence that some joint afferent fibres may take an 'ectopic' path to the central nervous system via a nearby muscle nerve. 2. Experiments were conducted in anaesthetized cats in which a distal extension of the indicis proprius nerve was observed to project beyond its own muscle to the dorsal surface of the wrist joint capsule which is also supplied by the 'classic' wrist joint nerve, a branch of the dorsal interosseous nerve. Both the proximal and distal segments of the indicis proprius nerve were exposed for recording, by means of silver hook electrodes, while each segment remained in continuity. 3. Individual wrist joint afferent fibres with receptive fields on the dorsal surface of the joint capsule could be identified electrophysiologically within the distal segment of the indicis proprius nerve. In each of these cases the same fibre could also be identified at the proximal recording site. The identity of each of these simultaneously recorded units was established (1) by the short fixed interval between their times of spike occurrence, (2) from the exact correspondence of the capsular receptive field for the simultaneously recorded spikes, and (3) by the unfailing correlation in the presence, or absence, of the distally and proximally recorded spikes in association with either manual or controlled stimulation of the wrist joint capsule. Most joint afferent fibres identified with this projection path were in the group II range of conduction velocities and had conventional properties but group III fibres also appeared to be represented. 4. The present demonstration that some joint afferent fibres may be located within 'muscle' nerves emphasizes the importance of activating deep inputs, of joint or muscle origin, by adequate stimulation of the peripheral receptors in order to examine selectively the central actions of either source of input. Electrical stimulation of the peripheral nerves may lead to interpretative ambiguities.

An intact peripheral nerve preparation for monitoring inputs from single muscle afferent fibres.

A preparation is described that permits the monitoring of activity from individual muscle afferent nerve fibres in an intact peripheral nerve in the forelimb of the cat. The nerve is a fine branch of the deep radial that supplies the indicis proprius muscle. When it is freed from nearby tissue over a length of 2-5 cm and placed in continuity over a silver hook electrode, it becomes possible to identify and monitor the impulse activity from each muscle afferent fibre activated by stretch or vibration applied to the muscle tendon or by focal mechanical stimulation of the muscle at the presumed site of individual spindle receptors. With this preparation it is possible to examine the central actions and security of transmission at central synaptic targets for single, identified muscle afferent fibres arising in the cat's forearm.

Quantitative analysis of cuneate neurone responsiveness in the cat in association with reversible, partial deafferentation.

1. Partial deafferentation, based on peripheral nerve section or local anaesthetic blockade, has been reported to induce both immediate loss of responsiveness and/or immediate reorganization in receptive fields of neurones in the somatosensory system. In the present study, in anaesthetized cats, we have used a rapid, reversible deafferentation procedure based on cold block of the median nerve in order to evaluate quantitatively the response characteristics of cuneate neurones (n = 39) before, during and after partial deafferentation. 2. The first hypothesis tested was that cuneate neurones with input from ulnar or superficial radial nerve fields in the vicinity of the median nerve field should undergo, in association with median nerve blockade, an increased level of responsiveness to tactile stimuli within the ulnar or radial nerve zone, and an expansion of their cutaneous receptive fields. However, among eighteen cuneate neurones of this type, there was no evidence for any systematic enhancement of responsiveness nor, in at least sixteen of the eighteen neurones, any evidence for receptive field expansion. 3. The second hypothesis tested was that cuneate neurones whose input came from both the median nerve and another peripheral nerve source should undergo, in association with median nerve blockade, an increase in responsiveness to the remaining input and an expansion of the receptive field into the field of that remaining nerve source. However, in none of thirteen neurones of this type tested was there evidence of such a change. 4. The third hypothesis was that cuneate neurones whose control' receptive fields were within the median nerve zone of deafferentation should show an emergence of novel receptive fields and responsiveness from areas around the field of innervation of the median nerve. However, in none of eight neurones of this type was there evidence for such changes in adjacent skin areas. 5. In conclusion, with the use of cold block of the median nerve for partial deafferentation, the present study has confirmed previous findings of denervation-related loss of responsiveness in dorsal column nuclei neurones. The conflicting findings in studies of central nervous system plasticity indicate the need to understand better factors that do and do not lead to acute central changes.

The effects of neonatal median nerve injury on the responsiveness of tactile neurones within the cuneate nucleus of the cat.

1. The capacity of cuneate neurones to attain normal functional properties following neonatal median nerve injury was investigated with single neurone recording in anaesthetized cats, 12-24 months subsequent to a controlled crush injury. Effectiveness of the peripheral nerve injury was confirmed by the abolition of the median nerve compound action potential following the crush. 2. Cuneate recording was carried out after denervation of the forearm, apart from the median nerve, to ensure that neurones studied had receptive fields within the distribution zone of the regenerated median nerve. Controlled and reproducible tactile stimuli were used to evaluate the functional capacities of neurones to determine whether they were consistent with those reported earlier for cuneate neurones in cats that had normal peripheral nerve development. 3. Twenty-two cuneate neurones with well-defined tactile receptive fields within the distribution zone of the regenerated median nerve were classified according to their adaptation characteristics and functional properties. Slowly adapting neurones responded throughout static skin indentations and had graded and approximately linear stimulus-response relations over indentation ranges up to 1.5 mm. Rapidly adapting neurones responded to the dynamic phases of skin indentations and could be divided into two broad classes, one most sensitive to vibrotactile stimuli at 200-400 Hz which appeared to receive a predominant input from Pacinian corpuscle receptors, and a non-Pacinian group that included neurones most sensitive to skin vibration at 5-50 Hz which appeared to receive glabrous skin input from the rapidly adapting class of afferent fibres. 4. Based on the stimulus-response relations and on measures of phase locking in the responses to vibrotactile stimuli, it appears that the functional properties of cuneate neurones activated from the field of a regenerated median nerve subsequent to a neonatal nerve crush injury were consistent with those reported previously for 'control' cuneate neurones. The results indicate that cuneate neurones can acquire normal tactile coding capacities despite the disruption caused by prior crush injury to their peripheral nerve source.