Cuneate Nucleus Of Cat Research Articles

Edge Computing in Nature: Minimal pre-processing of multi-muscle ensembles of spindle signals improves discriminability of limb movements.

Multiple proprioceptive signals, like those from muscle spindles, are thought to enable robust estimates of body configuration. Yet, it remains unknown whether spindle signals suffice to discriminate limb movements. Here, a simulated 4-musculotendon, 2-joint planar limb model produced repeated cycles of five end-point trajectories in forward and reverse directions, which generated spindle Ia and II afferent signals (proprioceptors for velocity and length, respectively) from each musculotendon. We find that cross-correlation of the 8D time series of raw firing rates (four Ia, four II) cannot discriminate among most movement pairs (∼ 29% accuracy). However, projecting these signals onto their 1st and 2nd principal components greatly improves discriminability of movement pairs (82% accuracy). We conclude that high-dimensional ensembles of muscle proprioceptors can discriminate among limb movements-but only after dimensionality reduction. This may explain the pre-processing of some afferent signals before arriving at the somatosensory cortex, such as processing of cutaneous signals at the cat's cuneate nucleus.

Evolution of morphological and histochemical changes in the adult cat cuneate nucleus following forelimb denervation.

Morphological and histochemical changes were studied in the ipsilateral cuneate nucleus between one and 52 weeks after forelimb denervation in adult cats. The deafferented nucleus and neighboring fasciculus were noticeably reduced in size within four weeks and decreased further by 13 weeks. The intensity of acetylcholinesterase staining decreased within one week and was further reduced one month after nerve transections. This reduction in acetylcholinesterase staining was transient, approaching control levels within one year. Parvalbumin immunostaining was also altered by the nerve transections; on the deafferented side, the neuropil staining in the cuneate nucleus and fasciculus decreased, but the number of parvalbumin-positive cells was consistently greater than in the contralateral side. These cell counts returned to normal levels within one year. One month after the injury, cytochrome oxidase activity was reduced. This reduction persisted and was even more apparent after one year. In parallel, the cell clusters of the nucleus became progressively less distinct. These observations in an adult mammal indicate that peripheral nerve injury imposes molecular and morphological changes on second-order sensory neurons which evolve differentially with time. Although some changes developed rapidly after deafferentation, the onset of others was slower; and whereas some seemed irreversible, others eventually regressed. Taken together with the functional studies of others, these findings suggest that early molecular changes observed in cuneate neurons reflect adaptive reactions to lesion-induced alterations in afferent activity. Permanent deprivation of the normal input, however, would eventually lead to chronic, and perhaps irreversible, degenerative changes.

Single fiber studies of ascending input to the cuneate nucleus of cats: II. Postsynaptic afferents

The morphology of single postsynaptic afferent fibers terminating in the feline cuneate nucleus was investigated by using transport of Phasolus vulgaris leucoagglutinin from the cervical spinal cord and intraaxonal injections of horseradish peroxidase into identified postsynaptic fibers in the cuneate fasciculus. Injections of Phaseolus in C5 and C6 of both rhizotomized and non-rhizotomized cats gave similar results and confirmed previous observations with other techniques. In one animal with the smallest injection and the fewest labeled fibers in the cuneate nucleus, ten individual collaterals were reconstructed from serial sections. Most of these collaterals were at middle levels of the cuneate (from obex to about 4 mm caudal to it); they were largely confined to the rim and ventral regions of the nucleus, and their terminal fields were restricted rostrocaudally. Electrophysiologically identified fibers stained with horseradish peroxidase had large receptive fields on the ipsilateral forepaw, and latencies suggesting an oligosynaptic link to the periphery. Most of the collaterals from these fibers were also at middle cuneate levels and terminated mainly at the periphery of the nucleus but gave rise to larger terminal arbors, including sparse terminal branches to the core of the nucleus. Individual postsynaptic fibers differed in several respects from primary afferent fibers. While the spacing of collaterals of postsynaptic fibers was intermediate between that of G hair and Ia fibers, their arbors were larger than either, and could extend through the dorsoventral extent of the cuneate nucleus. The pattern of bifurcation of postsynaptic fibers resulted in stringier arbors which encompassed larger and less dense terminal fields than those of primary afferents. The number of boutons per collateral was intermediate between G hair and Ia fibers, but boutons of postsynaptic fibers were substantially smaller. These morphological differences are consistent with distinct functional roles for the two main ascending afferent systems, as suggested by electrophysiological data.

Single fiber studies of ascending input to the cuneate nucleus of cats: I. Morphometry of primary afferent fibers

The morphology of afferent fibers ascending to the cuneate nucleus has been examined in this and the subsequent paper in order to quantify the pattern of arborization and bouton arrangement of selected classes of primary afferents and to compare these data with data from postsynaptic fibers ascending to the cuneate nucleus. Electrophysiologically identified G hair and Ia muscle afferent fibers in the cuneate fasciculus were intraaxonally injected with horseradish peroxidase. Cutaneous afferents terminated dorsal to proprioceptive afferents, especially at middle levels of the cuneate nucleus. The spacing of collaterals along G hair fibers was variable, but averaged 1.46 collaterals per mm; collateral density was higher at middle cuneate levels than in the rest of the nucleus. Collateral density of Ia fibers was lower than for G hair fibers and was lowest at caudal levels of the nucleus. Branches of G hair collaterals, though often initially diverging, usually converged to terminate in a single focus in the dorsal part of the nucleus. The probability of bifurcation of Ia collaterals decreased steadily at successive branch points. These collaterals branched less symmetrically than G hair collaterals, and terminated in the ventral cuneate with less dense arbors, stretched mediolaterally, but of comparable cross-sectional area. Individual G hair collaterals gave rise to more boutons than Ia collaterals; in both cases they were mostly of the en passant type. Boutons were restricted to distal branches of G hair collaterals, whereas boutons of Ia collaterals were also located on proximal branches. Bouton size was similar for the two classes of collaterals. The data reported here, in combination with the published literature, suggest that the collaterals of roughly 300 G hair fibers overlap at any given point at middle levels of the cuneate nucleus. This high degree of anatomical convergence is not predicted by the functional segregation described with electrophysiological mapping, implying the presence of intrinsic nuclear mechanisms enhancing response specificity.

Properties of proprioceptive neurons in the cuneate nucleus of the cat.

Fifty-two slowly adapting proprioceptive neurons in the cuneate nucleus of chloralose-anesthetized cats were studied. Recordings were made from 3 mm rostral to the obex to 5 mm caudal. The highest densities of proprioceptive neurons were found above and more than 3 mm caudal to the obex. Analysis of the spike trains produced with the forelimb held fixed revealed three basic periodic patterns. Neurons exhibiting these patterns were partitioned into three groups, referred to as the A, B, and C classes. Class A neurons (42%; 22/52) produced regular spike trains that were qualitatively similar to muscle spindle fibers. Interval distributions for this class were typically unimodal and slightly positively skewed. Adjacent intervals were frequently positively correlated. Spectral analysis suggested that 91% of class A spike trains had one to two periodic components. Class B neurons (21%; 11/52) had additional spikes interposed in their periodic discharge; these "interrupting" spikes did not significantly alter the timing of the dominant periodic discharge. Interval distributions were typically bimodal and adjacent intervals were negatively correlated. Spectral analysis suggested that two or more periodic components were present in their spike trains. Class C neurons (36%; 26/52) had spike trains with a basic rhymicity, but when this specific discharge was interrupted, the subsequent interval was near modal length; thus, they were "reset." Interval distributions were usually multimodal and adjacent intervals were frequently negatively correlated. Spectral analysis suggested that C spike trains usually had four or more periodic components. Estimates of information-carrying capacity of each class using a mean rate code and those of primary muscle spindle fibers suggested that a sizable information loss may occur in synaptic transmission. This potential loss was smaller for A-neurons (40%) than for B- (69%) or C-neurons (64%). Electrical stimulation of cutaneous structures influenced 55% (22/52) of the sample. All were members of the B and C classes. Responses were typically biphasic. The cutaneous receptive fields nearly always included a portion of the forepaw. No relationship was found between movement sensitivity and receptive field topography. Contralateral input was found in half (10/20) the neurons tested.

Peripheral and spinal inputs to physiologically identified thalamic and nonthalamic relay neurons in cat cuneate nucleus.

A single-unit population study of the feline cuneate nucleus was carried out to identify principal neuron types, their distribution within the nucleus, pattern of peripheral activation, and receptive field characteristics. Units were also tested for response to isolated dorsal column or dorsolateral funicular electrical stimulation. The nucleus was explored in a uniform pattern, and sample size was optimized by applying the search stimulus shocks to the dorsal spinal cord. Single units were defined as spinal afferents, cuneothalamic-relay (CTR) neurons, and non-cuneothalamic-relay (non-CTR) neurons. The following features were observed: The distribution within the nucleus of specific cell types agreed with cytoarchitectural studies: Spinal afferent fibers were superficial and caudal; 22% of neurons were CTR neurons; CTR neurons were most dense in the middle of the nucleus and were largely separate from non-CTR neurons. Of the 58 neurons tested for response to isolated dorsal column and dorsolateral funicular stimulation, 24% were activated from both tracts. Convergent input from the off-focus periphery (defined as other than the ipsilateral forelimb) was detected in both CTR and non-CTR neurons, most commonly from the contralateral forepaw. Several neurons were activated from three limbs. Thirty-seven percent of units were unresponsive to hair movement, touch, muscle palpation, or movement of joints. Compared to spinal fibers and non-CTR neurons, CTR neurons were most likely to have an identifiable input.

Intracellular staining study of the feline cuneate nucleus. I. Terminal patterns of primary afferent fibers.

The terminal arborizations of single identified cutaneous hair follicle and slowly adapting type I receptors and muscle (Ia) afferents have been studied in the cuneate nucleus of cats after intra-axonal injection of horseradish peroxidase. Penetrations were mainly at the middle and caudal levels of the nucleus--i.e., from obex to approximately 7 mm caudal to it. Following histochemical processing, the injected axons, along with their collateral branches and synaptic terminals, were visualized and examined with light and electron microscopy. Cutaneous afferents in middle cuneate (from obex to approximately 4 mm caudal to it) issued collateral branches, along the rostrocaudal axis of the nucleus, at intervals between 100 and 1,000 microns. The terminal field of each collateral's branches encompassed an area elongated largely rostrocaudally and virtually confined to the dorsal part of the middle cuneate. Although adjacent collaterals had nonoverlapping terminal arborizations, each one could give rise to separate foci of terminations. Muscle afferents differed, on the whole, from cutaneous afferents in the location and extent of collateral branching and terminal arborizations. However, because muscle fibers terminated primarily in the ventral region of the cuneate, but nevertheless exhibited sparser terminations in the dorsal part of the middle cuneate, there was some spatial overlap between zones of muscle and cutaneous projection. Synaptic boutons of cutaneous afferent fibers contained round clear vesicles, contacted dendritic profiles (sometimes more than one), and were postsynaptic to small boutons containing polymorphic vesicles. In contrast, boutons of muscle afferent fibers contacted somatic and dendritic profiles and were not postsynaptic to other boutons. The results are in general agreement with previous anatomical and electrophysiological work; however, the extent of the terminal field of single collateral branches may provide for a greater convergence of different receptor classes and of receptive fields on neurons in the middle cuneate than estimated by previous electrophysiological investigations.

Intracellular staining study of the feline cuneate nucleus. II. Thalamic projecting neurons

Morphological and physiological features of thalamic projecting neurons in the middle region of the cuneate nucleus of cats (from obex to 4 mm below it) have been studied, using intracellular recording and iontophoresis of horseradish peroxidase. All cuneothalamic neurons in the present sample) responded to movement of hairs on wrist, paw, or digits. However, approximately 50% of the neurons could be activated by other types of stimulation (e.g., light or maintained pressure on the skin, movement of claws, etc.). No clear differences were apparent in the physiological responses correlated with the varied dendritic pattern of stained neurons. Dendritic arborizations of most cuneothalamic neurons were more extensive than assumed previously, from Golgi impregnated material. As a consequence, only a few neurons have dendrites ramifying within a restricted region--i.e., corresponding to a typical cluster of the middle cuneate nucleus. Dendrites extending in various directions and spanning a distance up to 500 microns provide cuneothalamic neurons with the ability to receive input from relatively widespread areas. Collateral branches of axons of cuneothalamic neurons were observed in 50% of the stained neurons. Most of these collaterals terminated ventrally within the cuneate nucleus. Extensive collateral arborizations were observed in the dorsal as well as the ventral cuneate. These results, together with those reported in the previous paper, suggest complex interactions of afferent inputs on cuneothalamic neurons. In particular, such neurons are likely to be influenced by convergent input from different receptor classes and, because of their axonal collaterals, probably affect the excitability of other neurons, projecting or intrinsic, in their immediate vicinity or in other nuclear regions.

Liminal and supraliminal response characteristics of mechanoreceptive neurons in the cuneate nucleus of cat.

The response characteristics of mechanoreceptive neurons (RA, SA, and PC) innervating the foot pad of cat were determined in the cuneate nucleus. The mechanical stimuli were single sinusoidal pulses of varying frequency (20, 60, 150, and 240 Hz), and vibratory trains of varying frequency (80 and 240 Hz) and duration (50, 100, and 400 ms). Thresholds and stimulus-response functions were determined with single pulses. Absolute thresholds (1 impulse/train), tuning thresholds (1 impulse/cycle), and atonal intervals (the range between absolute and tuning thresholds) were determined with vibratory stimulus trains. When tested with single pulses the thresholds resembled those of primary afferents in all unit populations. The stimulus-response function of PC units but not of all RA units were comparable to those of primary afferents. Noxious conditioning stimulation did not influence the thresholds of cuneate mechanoreceptors in the tested sample (N = 6). Mostly PC units were tested with vibratory trains. Absolute thresholds were not dependent on stimulus duration, which is a consistent finding with peripheral units. In contrast to peripheral units, the tuning thresholds in most PC units were elevated with increasing stimulus duration. The variability in the range of atonal intervals was much larger than in the periphery. Thus, it seems that both the type of the tactile signal and the type of the studied mechanoreceptive neuron are critical parameters in determining whether the response characteristics of neurons in the cuneate and in the periphery are identical or not.

Detection by HPLC-EC of primary amines recovered in aqueous push-pull perfusates from cat cuneate nucleus.

A method is described for the quantitative detection of primary amines - particularly free amino acids - recovered in aqueous push-pull perfusates obtained from the cat cuneate nucleus. Isoindole derivatives of primary amine groups are formed by precolumn reaction with o-phthalaldehyde and mercaptoethanol. Derivatized sample components are separated and detected using HPLC with electrochemical detection. Of 22 amino acids standards studied individually, 12 were detectable under the conditions described. Variability of elution times and detector output peak heights were less than 2% and less than 10%, respectively. Concentration curves were linear to the 10 picomole order of magnitude. For cuneate nucleus perfusates, samples recovered during continuous peripheral somatosensory stimulation contained detectable derivative levels elevated above those of control samples. Sources of error in data interpretation are discussed.

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.

Differences in glial and neuronal labeling following [ 3H]proline or [ 3H]leucine injections into the dorsal column nuclei of cats

The differential incorporation of the amino acids proline and leucine by cells in the cat cuneate nucleus was investigated with electron microscopic autoradiography. Following [ 3H]leucine injections into the cuneate nucleus, all neurons located in either its clusters or non-clusters portion were densely labeled. In contrast, following [ 3H]proline injections, no neurons, regardless of their size and shape, were densely labeled in the clusters region. In the non-clusters region, some smaller neurons were labeled, but only at a moderate density. At all [ 3H]proline injection sites outside the area damaged by the pipette, the only densely-labeled cells were macroglial cells, both astrocytes and oligodendrocytes. Some densely labeled macroglial cells were also found at [ 3H]leucine injection sites, but fewer than at [ 3H]proline injection sites. Microglial cells were at most only sparsely labeled at both sites. These results suggest that most of the ‘small cells’ which were densely labeled by [ 3H]proline in earlier light-microscopic experiments ( Künzle & Cuénod, 1973; Felix & Künzle, 1974; Berkley, 1975; Groenewegen & Voogd, 1977) are macroglial cells. The preferential incorporation of [ 3H]proline by macroglial cells in the cuneate nucleus could be taken to indicate that proline serves as a neurotransmitter in the cuneate nucleus, either directed towards or produced by its neurons. Although the results of other experiments so far do not support this suggestion, they are insufficient to eliminate it. It is also possible that the unusual [ 3H]proline uptake pattern reflects regional variations in neuronal or glial metabolic needs. These and a number of other possible explanations for proline's incorporation pattern are discussed but none of them is as yet more appropriate than the others. Whatever the explanations prove to be, the results have implications for the use of proline in auto-radiographic tracing studies of neuronal projections. As shown earlier, unlike [ 3H]leucine, [ 3H]proline alone cannot always be relied upon to demonstrate all of the projections of a group of neurons. In addition, although neurons in the clusters region of the cuneate nucleus fail to be densely labeled by [ 3H]proline, dense labeling still can be observed in one of the terminal targets of the cuneate nucleus, the inferior olive ( Berkley, 1975). This result suggests that, along with neurons, glial cells may also be involved in the transfer of certain incorporated amino acids from one region of the brain to another.

Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus.

The effects of diazepam, flunitrazepam, phenobarbitone and baclofen on excitatory as well as on pre- and postsynaptic inhibitory processes in the cuneate nucleus were studied in decerebrate cats. Afferent presynaptic inhibition in the cuneate nucleus, evoked by volleys in the median nerve, and assessed by the size of the positive cuneate surface potential (P wave), the dorsal column reflex (DCR), and the increased excitability of primary afferent terminals of the ulnar nerve, was markedly enhanced by diazepam (0.1-3.0 mg/kh i.v.) and flunitrazepam (0.01-0.3 mg/kg i.v.), slightly enhanced by lower doses of phenobarbitone (3-20 mg/kg i.v.), but depressed by baclofen (1-10 mg/kg i.v.). Diazepam, flunitrazepam and phenobarbitone also increased postsynaptic inhibition in the cuneate nucleus which was measured by the decrease after conditioning volleys in the median nerve of the short-latency lemniscal response to cuneate stimulation. The GABA receptor blocking agent, picrotoxin, antagonized the effects of diazepam on pre- and postsynaptic inhibition in a surmountable way. After thiosemicarbazide (TSC), an inhibitor of GABA synthesis, both pre- and postsynaptic inhibition were greatly reduced and the augmenting effect of diazepam on both types of inhibition was nearly abolished. Aminooxyacetic acid (AOAA), an inhibitor of GABA degradation, slightly enhanced pre- and postsynaptic inhibition; the effects of diazepam were unaffected by AOAA. Diazepam, flunitrazepam and phenobarbitone did not alter the resting excitability of primary afferent endings or of cuneo-thalamic relay (CTR) cells in the cuneate nucleus. After higher doses (30 mg/kg i.v.) of phenobarbitone pre- and postsynaptic inhibition, which were enhanced by 10 mg/kg of this drug, tended to return to pre-drug values or below. Phenobarbitone, in contrast to benzodiazepines, also depressed in a dose-dependent way the N wave, which is an index of the orthodromic excitation of the CTR cells. Baclofen strongly depressed the cuneate N wave, decreased the excitability of CTR cells, reduced pre- and postsynaptic inhibition, but had no effect on the resting excitability of primary afferent endings. Our findings suggest the following modes of action of the above mentioned drugs: 1. benzodiazepines enhance selectively the GABA-mediated pre- and postsynaptic inhibition in the cuneate nucleus; 2. phenobarbitone slightly enhances pre- and postsynaptic inhibition only in a narrow dose range, and in addition reduces the excitatory processes in the cuneate nucleus; 3. baclofen seems to depress the excitation of cuneate relay cells and interneurones postsynaptically; the depression of relay cells is probably nonspecific.

Antagonism of gamma-aminobutyric acid and glycine by convulsants in the cuneate nucleus of cat.

1. Some convulsant substances have been applied to single neurones in the cat cuneate nucleus by microiontophoresis. Numerical values were derived for the effectiveness and selectivity of the substances as antagonists of gamma-aminobutyric acid (GABA) and glycine. 2. (+)-Bicuculline methochloride was the most effective GABA antagonist and it also excited many neurones. It antagonized GABA in 93% of experiments but also antagonized glycine in 41% of experiments. In most experiments the antagonism of GABA was greater than the antagonism of glycine resulting in an overall selective antagonism of GABA that was statistically significant. Nevertheless, in only about one quarter of the individual experiments was the GABA antagonism substantial and the selectivity clearcut. 3. (+)-Bicuculline and picrotoxin were less easily applied to neurones by microiontophoresis and were found to antagonize GABA in 30% and 35% of experiments, respectively. They also antagonized glycine in 25% and 30% of experiments, respectively. Overall, neither substance could be shown to be selective, statistically, although in the few individual experiments where the GABA antagonism was substantial the antagonism was clearly selective. 4. (+)-Tubocurarine antagonized GABA in 59% and glycine in 32% of experiments and it also excited many neurones. Penicillin antagonized GABA in 33% of experiments without antagonizing glycine. Neither antagonist caused any substantial antagonisms of GABA and neither showed significant selectivity overall. (-)-Bicuculline methochloride, leptazol and bemegride antagonized GABA or glycine in less than 10% of experiments, although (-)-bicuculline methochloride excited most neurones. 5. Strychnine antagonized glycine in every experiment while antagonizing GABA in only 5% of experiments. In each individual experiment the antagonism of glycine was substantial and clearly selective, resulting in a statistically significant selectivity overall. 6. It is concluded that the selective glycine antagonist strychnine is considerably better than the presently available GABA antagonists for distinguishing between responses to GABA and glycine, when the antagonists are applied by microiontophoresis.

Population analysis of single units in the cuneate nucleus of the cat

Population analysis has been used to investigate the properties of cells in the cuneate nucleus of the chloralose-anesthetized cat. Postsynaptic units were grouped on the basis of the maximum frequency following to ipsilateral superficial radial nerve stimulation, the degree of convergence onto cells from central and peripheral sources, and the response to natural stimulation of the ipsilateral forelimb. The groups were analyzed further on the basis of depth in the brainstem, initial spike latency, and variability in the initial spike latency in response to stimulation of the ipsilateral forelimb. Maximum order to the data resulted when the cells were grouped on the basis of maximum frequency following ability. The possible role of the defined cell groups in production of primary afferent depolarization (PAD) was examined by constructing simulated PAD time course curves. Both a rapidly rising time course curve, typical of ipsilateral forelimb activation, and a slowly rising curve, typical of “off-focus” activation, could be obtained by linearly summing unit depolarizations in a temporal pattern defined by measured spike latencies to the appropriate input. This, and other evidence, suggest that the observed properties of cuneate inhibition can be accounted for by the activity of cells within the cuneate nucleus. A wiring diagram for cuneate inhibition circuitry is presented.

Effects of projected cortical epileptiform discharges on unit activity in the cat cuneate nucleus

Recordings of single cells in the cuneate nucleus were made during cortical epileptiform activity. Spontaneous and evoked spiking activity of relay cells was primarily inhibited by the corticofugal epileptiform discharge. Most interneurons were inhibited, but a large proportion also showed an early excitatory corticofugal input. The EPSPs and IPSPs induced by corticofugal discharges were seen in intracellular and quasi-intracellular recordings of cuneate neurons. The observation of IPSPs, and the effectiveness of corticofugal input in inhibiting unit injury discharges and glutamate-induced firing, showed that corticofugal inhibition in cuneate was at least partially postsynaptic. Most cuneate neurons studied during cortical ictal episodes discharged in a fashion consistent with their responses to cortical interictal activity; i.e., units that had been inhibited were inhibited during the ictus and those that had been excited fired during the cortical seizure. Some units were gradually recruited by corticofugal input during seizure, but since most such units were interneurons, cuneate did not provide a positive feedback to the cortical focus. The corticocuneate pathway appeared to provide a negative feedback circuit which may be used to modulate transmission of sensory input.

Effects of projected cortical epileptiform discharges on field potentials in the cat cuneate nucleus

The effects of cortical epileptiform discharges on cuneate nucleus were investigated by studying cuneate field potentials evoked by corticofugal input. Cortical events triggered a negative-positive field potential sequence on the cuneate surface analogous to that evoked by forepaw nerve stimulation. Interaction of nerve-evoked potentials in the corticofugally induced positivity resulted in an amplitude decrease of the nerve potential, especially of its positive wave. Laminar analysis of the corticofugally evoked field potential suggested that its surface positive wave consisted of two components generated at different depths in cuneate; these two components were discussed as possible field potential signs of presynaptic and postsynaptic inhibition in cuneate. The influence of corticofugal discharges on transmission of sensory information through the cuneate nucleus was determined to be inhibitory, for nerve-evoked field potentials in the cuneate output pathway (medial lemniscus) were depressed during cortical epileptiform events.

On the pharmacology of the gamma-aminobutyric acid receptors on the cuneo-thalamic relay cells of the cat.

1. gamma-Aminobutyric acid (GABA) and glycine applied by iontophoresis were equipotent depressants of cuneo-thalamic relay neurones isolated from the middle third of the cuneate nucleus of cats either decerebrated or anaesthetized with sodium pentobarbitone.2. Glycine 13+/-2 nA and GABA 20+/-2 nA were equipotent depressors of hair cells (n=22) and, bicuculline applied by iontophoresis caused a parallel shift to the right of the GABA but not the glycine log-current response curves. The GABA equipotent dose-ratio was 2.0+/-0.2 for bicuculline currents of approximately 144 nA lasting about 11 min in cells excited either transynaptically by peripheral stimulation or postsynaptically by glutamate.3. Although a maximal bicuculline current seldom caused a significant shift of the glycine-log current response curve, many of our records show the onset of the glycine response to be slowed by doses in excess of 84 nA.4. Bicuculline also antagonized depressions by beta-guanidinopropionic acid, and delta-aminovaleric acid which mimicked the action of GABA.5. When tested on the same neurone, bicuculline and picrotoxin applied by iontophoresis were equipotent and their effects appear to be additive.6. The GABA sensitivity was not modified by repetitive (5 or 6) doses of i.v. bicuculline (0.2 mg/kg).7. The antagonism of GABA by bicuculline and picrotoxin appears to be of sufficient specificity to enable the separate roles of GABA and glycine as putative inhibitory transmitters of cuneo-thalamic relay cells to be determined.

Thalamic and cerebellar influence on single units of the cat cuneate nucleus

The activity of single units was extracellularly recorded from cuneate nucleus in cats anesthetized with Nembutal. Stimulation by trains of four impulses, 300/sec, of nonspecific thalamic nuclei and cerebellar fastigial nuclei could modify the spontaneous and evoked activity of both interneurons and relay cells. The peripherally evoked and spontaneous activity of CTR neurons were depressed for 150–200 msec after thalamic and cerebellar stimuli in, respectively, 40 and 30% of the cells while the antidromic lemniscal potential was never affected by these stimuli. Both excitatory and inhibitory effects were detected on cuneate interneurons after thalamic and cerebellar stimulations. The nonspecific thalamic nuclei stimulation evoked potentials in 70% of the interneurons and the fastigial nuclei in 40%. Most of the analyzed interneurons showed a characteristic convergence of peripheral and central (cortical, thalamic, reticular, cerebellar) excitatory and inhibitory effects. In interaction experiments both cerebellar and thalamic (conditioning) stimuli could inhibit the activity evoked by different test (cortical, reticular, and peripheral nerves) stimuli, at intervals of 10–200 msec. Inhibitory effects between cerebellar and thalamic stimulations were also observed. These results show that both nonspecific thalamus and cerebellum presynaptically control the sensory cuneate nucleus transmission through the effect exerted on the cuneate interneurons. This effect is considered to be mediated by the brain stem reticular formation.