On the probable absence of GABA receptors on the terminations of motor axon collaterals in the cat spinal cord

Summary When administered microelectrophoretically, GABA and the GABA-mimetic piperidine-4-sulphonic acid (P4S) appear to have no direct hyperpolarizing or depolarizing effect on the terminations of motor axon collaterals excited electrically in the ventral horn of the lumbar spinal cord of the cat. This lack of effect on axon terminals of motoneurones, which contrasts with the bicuculline-sensitive depolarization by P4S of the spinal terminals of primary afferent fibres, is consistent with previous reports of the probable absence of pharmacologically detectable GABA receptors on the spinal terminals of other central excitatory neurones, namely those of the red and lateral vestibular nuclei.     

Selective effects of (−)-baclofen on spinal synaptic transmission in the cat

Summary When ejected microelectrophoretically near spinal interneurones of cats anaesthetised with pentobarbitone and under conditions where postsynaptic excitability was maintained artificially at a constant level, (–), but not (+), -baclofen selectively reduced monosynaptic excitation by impulses in low threshold muscle (Ia and Ib) and cutaneous (A) afferents. Polysynaptic excitation of interneurones and Renshaw cells by impulses in higher threshold afferents was less affected, and baclofen had little or no effect on the cholinergic monosynaptic excitation of Renshaw cells. Glycinergic and gabergic inhibitions of spinal neurones were relatively insensitive to baclofen. These stereospecific actions of baclofen, produced by either a reduction in the release of excitatory transmitter or postsynaptic antagonism, suggest that Ia, Ib, and A afferents may release the same excitatory transmitter which differs from that of spinal excitatory interneurones.Microelectrophoretic (–), but not (+), -baclofen also reduced primary afferent depolarization of ventral horn Ia extensor afferent terminations produced by impulses in low threshold flexor afferents, without altering either the electrical excitability of the terminations or their depolarization by electrophoretic GABA or L-glutamate. This stereospecific action of baclofen is interpreted as a reduction in the release of GABA at depolarizing axo-axonic synapses on Ia terminals.     

Post-tetanic influences on primary afferent depolarization in the cat spinal cord

Summary In the spinal cord of pentobarbitone anaesthetised cats, increases in the electrical threshold of the terminations of extensor muscle group Ia afferent fibres, produced by tetanic stimulation of either the appropriate peripheral nerve or the central termination, were associated with parallel changes in the bicuculline-sensitive reduction in electrical threshold of the termination produced synaptically by impulses in flexor muscle low threshold afferent fibres (primary afferent depolarization, PAD) or by microelectrophoretic piperidine-4-sulphonic acid (P4S), an analogue of GABA. Since this post-tetanic hyperpolarization (PTH) could be produced by tetanic stimulation of a single termination centrally, and not by peripheral stimulation of heteronymous nerves, it presumably resulted from changes intrinsic to the tetanized termination. Increases in PAD and the effectiveness of P4S were probably associated with post-tetanic activation of an electrogenic Na⁺/K⁺ pump as the predominant cause of PTH, whereas decreases may have been largely the consequence of post-tetanic increases in intracellular Ca²⁺ levels. These results provide further evidence that GABA is the depolarizing transmitter at axo-axonic synapses upon primary afferent terminals, and that the underlying membrane conductance increase has a reversal potential at a more depolarized level than the resting potential.     

The dual effects of GABA and related amino acids on the electrical threshold of ventral horn group Ia afferent terminations in the cat

Summary Amino acids were administered microelectrophoretically near the unmyelinated terminations of extensor muscle Ia afferent terminations stimulated electrically in the vicinity of lumbar motoneurones in anaesthetized cats. The predominant effect of one group (structurally related to GABA, poor substrates for in vitro amino acid uptake systems) was a reduction in the threshold (depolarization). The second group (including GABA and structural analogues which are substrates for GABA transport systems in vitro) had biphasic effects, an initial reduction being followed by an increase in threshold. The third group (structurally unrelated to GABA, substrates for amino acid uptake systems) only increased Ia termination thresholds.Reductions in termination thresholds, but not increases, were associated with diminution of synaptically evoked primary afferent depolarization, and were decreased by bicuculline methochloride. Many amino acids increased the electrical resistance of the intraspinal medium near the orifices of the barrels of seven barrel micropipettes, and for L-histidine, one of the third group of amino acids, both this effect and the increased threshold of terminations were reversibly modified by microelectrophoretic ouabain.These observations suggest that GABA-mimetics depolarize Ia terminations by interacting with bicuculline-sensitive receptors similar to those at hyperpolarizing gabergic synapses upon spinal interneurones. In addition, under the experimental conditions used, these and other amino acids increase termination thresholds, probably in the absence of any change in membrane conductance, an effect resulting from alterations in the ionic constitution of the extracellular medium around the orifices of micropipettes ejecting amino acids consequent upon the ouabain-sensitive co-transport of amino acids and sodium ions into neurones and glia.     

The differential effects of baclofen on segmental and descending excitation of spinal interneurones in the cat

Summary Intravenous baclofen (1–6.25 mg kg^-1) substantially reduced the monosynaptic excitation of neurones in the intermediate nucleus of the cat spinal cord by impulses in group I extensor muscle primary afferent fibres, but had little or no effect on excitation by stimulating fibres of the ipsilateral dorsolateral funiculus or the contralateral red nucleus. Relatively low concentrations of baclofen thus appear not to influence the release of excitatory transmitter from the terminals of rubrospinal, corticospinal and long descending propriospinal fibres, in contrast to the reduction of the release of primary afferent transmitters.     

Prolonged GABAB receptor-mediated synaptic inhibition in the cat spinal cord: an in vivo study

In pentobarbitone-anaesthetised spinal cats, a comparison was made of the effects of intravenous bicuculline hydrochloride, a GABA_A-receptor antagonist, and several (-)-baclofen (GABA_B-receptor) antagonists (CGP 35348, 46381, 56999A) on the prolonged inhibition of extensor-muscle monosynaptic reflexes, recorded from lumbar ventral roots, by brief or continuous tetanic stimulation of low-threshold afferent fibres of hindlimb flexor muscles. Two components of brief tetanus inhibition were detected. Whilst possibly of similar central latency, the inhibition associated with GABA_B receptors had a longer time course than that reduced by bicuculline. Furthermore, whereas bicuculline reduced primary afferent depolarization, generated by the inhibitory volleys, and detected as dorsal-root potentials, such potentials were generally enhanced by intravenous baclofen antagonists. The inhibition of reflexes during and after continuous (333 Hz) tetanic flexor-nerve stimulation appeared to be predominantly associated with the activation of GABA_B receptors. In the period following continuous tetanic flexor-nerve stimulation, during which monosynaptic extensor reflexes were reduced in amplitude, the action potentials of the intraspinal terminations of extensor-muscle group-Ia afferent fibres were reduced in duration, as detected by the time course of the recovery of the threshold to extracellular microstimulation following the arrival of an orthodromic impulse. A reduction in termination action-potential duration also accompanied the reduction by microelectrophoretic (-)-baclofen of the release of excitatory transmitter from group-Ia terminations, both presynaptic effects being blocked by microelectrophoretic baclofen antagonists. However, the reduction of the duration of the action potential of individual group-Ia terminations, which followed continuous flexor-nerve stimulation, was not sensitive to the baclofen antagonist CGP 55845A, but was diminished by bicuculline methochloride. Intravenously administered bicuculline hydrochloride, however, had little or no effect on the inhibition of reflexes following continuous flexor-nerve stimulation. These observations are discussed in the context of possible intraspinal pathways and pre- and postsynaptic mechanisms for GABA_A and GABA_B receptor-mediated inhibition of the monosynaptic excitation of spinal motoneurones and of the functional significance of central GABA_B receptor-associated inhibitory processes, given the relatively minimal effects on motor activity and behaviour produced by baclofen antagonists that penetrate the mammalian blood-brain barrier. Received: 2 July 1997 / Accepted: 30 January 1998     

Baclofen: reduction of presynaptic calcium influx in the cat spinal cord in vivo

 In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, microelectrophoretically administered (–)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (–)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (–)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (–)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (–)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (–)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (–)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (–)-baclofen and the different sensitivities of transmitter release at various central synapses. Received: 30 May 1996 / Accepted: 11 September 1996     

The depolarization of feline ventral horn group Ia spinal afferent terminations by GABA

Summary The unmyelinated terminal regions of extensor muscle Ia afferent fibres were stimulated electrically near lumbar motoneurones in anaesthetised cats using 300 s pulses of less than 1 A passed through the central NaCl barrel of seven barrel micropipettes. Such terminations were identified by anodal blocking factors of less than four and the latency of the antidromic impulse recorded in the appropriate peripheral muscle nerve.Although the effects of microelectrophoretically administered GABA were occasionally complex, the most consistent finding was a reduction in termination threshold followed by an increase. Both this reduction in threshold by GABA, and that produced by tetanic stimulation of low threshold flexor afferents (PAD) were diminished by microelectrophoretic bicuculline methochloride. This GABA antagonist alone elevated the threshold of some terminations but did not reduce the depolarizing action of either potassium or L-glutamate. Furthermore, since reductions in threshold by GABA, but not by either potassium or L-glutamate, were associated with a decrease in PAD, GABA appears to increase terminal membrane conductance.Since neither GABA nor bicuculline methochloride influenced the threshold or afferent depolarization of non-terminal regions of Ia fibres, these results are consistent with the function of GABA as a depolarizing transmitter at gabergic axoaxonic synapses upon the terminals of Ia afferent fibres synapsing with motoneurones.     

Cortically evoked pre-and postsynaptic inhibition of impulse transmission to the dorsal spinocerebellar tract

Summary Synaptic actions evoked from primary afferents and the sensorimotor cortex in neurones of the dorsal spinocerebellar tract were investigated: 1. Stimulation of the anterior lobe of the cerebellum produced a small IPSP in only one but not in the other six neurones examined. 2. IPSPs were induced not only from group I fibres (in 41% of group I neurones) but also from cutaneous and/or high threshold muscle afferents (in 37%). 3. Stimulation of the contralateral sensorimotor cortex evoked IPSPs in 80% of group I neurones. The IPSP had a latency of 10–15 msec and lasted for 40–100 msec. EPSPs were evoked from the cortex in a small number of neurones. 4. Effects from the cortex were compared with those from primary afferents in individual neurones. The cortical IPSPs were induced independently of whether the neurone received monosynaptic EPSP from extensor or flexor group I fibres. The cortical IPSPs (or EPSPs) occurred more frequently in neurones which exhibited polysynaptic IPSPs (or EPSPs) from primary afferents. 5. The few FRA neurones encountered were all excited from the cortex.Excitability measurements of primary afferent terminals in or near Clarke's column showed that a terminal depolarization is evoked from the cortex in group Ib but not in Ia afferents.The relative importance of post-and presynaptic inhibition of transmission to the DSCT is discussed.     

Baclofen antagonism by 4-amino-3-(5-methoxybenzo[b]furan-2-yl) butanoic acid in the cat spinal cord

When administered microelectrophoretically, 4-amino-3-(5-methoxybenzo[b]furan-2-yl)butanoic acid (MBFG) reversibly reduced the presynaptic depression by (−)-baclofen of the monosynaptic excitation of spinal interneurones by impulses in muscle low-threshold afferent fibres of the cat as well as the postsynaptic depression by (−)-baclofen of the firing of these neurones. MBFG, as an antagonist of (−)-baclofen, may be useful in investigating the structure-activity relationships of central and peripheral baclofen receptors.     

Phosphinic acid derivatives as baclofen agonists and antagonists in the mammalian spinal cord: an in vivo study

The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre-and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35 348, 36 742, 46 381, 52 432, 54 626 and 55 845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABA_A agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre-and postsynaptic inhibitory effects of 3-aminopropyl-methyl-osphinic acid (CGP 35 024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35 024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABA_B receptors. Spinal pre-and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55 845 and 46 381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.     

Baclofen antagonism by 2-hydroxy-saclofen in the cat spinal cord

When administered microelectrophoretically, a sulphonic acid derivative of baclofen, 3-amino-2-(4-chlorophenyl)-2-hydroxy-propylsulphonic acid, reversibly reduced the presynaptic reduction by (-)-baclofen of the monosynaptic excitation of spinal interneurones by impulses in low threshold primary afferent fibres of the cat as well as the postsynaptic depression by (-)-baclofen of the firing of these neurones. This compound, 2-hydroxy-saclofen, may be useful in assessing the physiological significance of central baclofen receptors.     

Differential action of (−)-baclofen on the primary afferent depolarization produced by segmental and descending inputs

Summary The purpose of the present series of experiments was to analyze, in anesthetized and paralyzed cats, the effects of (-)-baclofen and picrotoxin on the primary afferent depolarization (PAD) generated in single Ib afferent fibers by either intraspinal microstimulation or stimulation of the segmental and descending pathways. PAD was estimated by recording dorsal root potentials and by measuring the changes in the intraspinal activation threshold of single Ib muscle afferent fibers. The PAD elicited by stimulation of group I muscle or cutaneous afferents was readily depressed and often abolished 20–40 min after the intravenous injection of 1–2 mg/kg (-)-baclofen. In contrast, the same amounts of (-)-baclofen produced a relatively small depression of the PAD elicited by stimulation of the brainstem reticular formation (RF). The monosynaptic PAD produced in single Ib fibers by intraspinal microstimulation within the intermediate nucleus was depressed and sometimes abolished following the i.v. injections of 1–2 mg/kg (-)-baclofen. Twenty to forty minutes after the i.v. injection of picrotoxin (0.5–1 mg/kg), there was a strong depression of the PAD elicited by stimulation of muscle and cutaneous afferents as well as of the PAD produced by stimulation of the RF and the PAD produced by intraspinal microstimulation. The results obtained suggest that, in addition to its action on primary afferents, (-)-baclofen may depress impulse activity and/or transmitter release in a population of last-order GABAergic interneurons that mediate the PAD of Ib fibers. The existence of GABA_b autoreceptors in last-order interneurons mediating the PAD may function as a self-limiting mechanism controlling the synaptic efficacy of these interneurons.     

An in vivo electrophysiological investigation of group Ia afferent fibres and ventral horn terminations in the cat spinal cord

An extracellular microstimulation technique has been used to investigate and compare the properties of group I primary afferent myelinated fibres in the dorsal column and group Ia unmyelinated terminations in the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium. Fibres were distinguished from terminations on the basis of location, anodic blocking factor and sensitivity to GABA_A mimetics. The recovery curves of threshold following an orthodromic impulse provided an estimate of both action potential duration and rate of repolarization. The action potentials of group Ia terminations were of briefer duration (by a factor of approximately 2) with more rapid rates of repolarization (factor of approximately 3) than those of the myelinated fibres. The prolongation of termination but not fibre action potentials by microelectrophoretic tetraethylammonium and 4-aminopyridine indicated the presence of voltage-activated potassium channels in the termination membrane. Differences in the effects on Ia termination action potentials of depolarizations (reductions in threshold) associated with a preceding action potential, synaptically released GABA, microelectrophoretic piperidine-4-sulphonic acid or dl-homocysteic acid suggest that an increase in termination membrane conductance is the major factor in the reduction of transmitter release during the activation of presynaptic GABA_A receptors.     

Differential effects of (−)-baclofen on Ia and descending monosynaptic EPSPs

Summary 1. In cats anesthetized with alpha-chloralose, population synaptic responses of motoneurons produced by stimulation of group I afferents were recorded from ventral roots with a sucrose gap or extracellularly from the motor pool. These responses were depressed, and often abolished, following the intravenous injection of 1–3 mg/kg of (–)-baclofen, a presumed GABA_b agonist. 2. The monosynaptic population responses of motoneurons produced by stimulation of the ipsilateral ventromedial funiculus (VMF), the bulbar reticular formation or the vestibular nucleus, were also depressed following the administration of (–)-baclofen, but to a lesser degree than responses produced by stimulation of group I fibers. 3. Depression of the synaptic actions of Ia and of descending fibers following the administration of (–)-baclofen occurred without significant changes in the presynaptic volley recorded from the cord dorsum. However, in 3/4 experiments the intraspinally recorded Ia terminal potential was reduced following the injection of (–)-baclofen. The VMF terminal potentials were also depressed, but to a lesser degree. 4. Intracellular recordings from spinal motoneurons indicate that the (–)-baclofen-induced depression of the monosynaptic Ia- and VMF-EPSPs occurred without important changes in the time course of EPSP decay. This suggests that with the amounts used, postsynaptic changes were not contributing significantly to the EPSP depression. 5. It is suggested that (–)-baclofen depresses synaptic transmission probably by activation of GABA_b receptors located at the intraspinal terminations of Ia and descending fibers. The lower sensitivity of VMF actions to (–)-baclofen would be accounted for by a relatively low density of baclofen receptors in descending fiber terminals.     

Effects of γ-aminobutyrate and bicuculline on primary afferent depolarization of cutaneous fibres in the cat spinal cord

The excitability of single cutaneous primary afferent fibres (sural nerve) was tested by focal stimulation in the dorsal horn of the cat spinal cord, and recording the antidromically conducted action potential in the peripheral nerve. To induce primary afferent depolarization, which is an expression of presynaptic inhibition, the superficial peroneal nerve was stimulated. The primary afferent depolarization was measured as the concomitant excitability change in the antidromically excited sural fibre. This primary afferent depolarization was reduced by 32% during microelectrophoretic release of bicuculline methochloride near the microstimulation electrode in the dorsal horn. Microelectrophoresis of γ-aminobutyrate increased excitability in sural nerve fibres which correlated with the primary afferent depolarization induced by stimulation of the superficial peroneal nerve.The results suggest a possible role for γ-aminobutyrate in presynaptic inhibition of cutaneous afferent fibres in the cat.     

Comparison of effects of monoamines on transmission in spinal pathways from group I and II muscle afferents in the cat

Summary The actions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT; serotonin) were compared with those of L-3,4-dihydroxyphenylalanine methyl ester (Methyl-L-DOPA) on transmission to spinal interneurones in mid-lumbar (L4 and L5) segments of the cat spinal cord. The drugs were applied ionophoretically and their effects were tested on monosynaptic field potentials evoked by nerve impulses in hindlimb group I and group II muscle afferent fibres and on responses of interneurones with synaptic input from these fibres. Of field potentials recorded at various locations, both NA and 5-HT depressed those evoked from group II fibres in the intermediate and ventral horn regions of the spinal cord but not, or only occasionally, in the dorsal horn. Field potentials of group I origin were not depressed. The tested interneurones were located where group II field potentials were affected. NA, 5-HT and Methyl-L-DOPA depressed responses to electrical stimulation of group II fibres but not responses evoked by group I fibres. The depression consisted of an increase in the latency and a decrease in the number of action potentials evoked by the stimuli. All three drugs were also found to decrease the amplitude of intracellularly recorded monosynaptic EPSPs of group II origin but not of monosynaptic EPSPs evoked in the same neurones by group I fibres. Interneuronal firing induced by DL-homocysteic acid was depressed as effectively as responses to electrical stimulation of peripheral nerves. The possibility of presynaptic and/or postsynaptic mechanisms of the selective depression of synaptic actions of group II origin are discussed.     

Light and electron microscopy of contacts between primary afferent fibres and neurones with axons ascending the dorsal columns of the feline spinal cord

In addition to primary afferent fibres, the dorsal columns of the cat spinal cord contain ascending second-order axons which project to the dorsal column nuclei. The aim of the present study was to obtain morphological evidence that certain primary afferent axons form monosynaptic contacts with cells of origin of this postsynaptic dorsal column pathway. In ten adult cats, neurones with axons ascending the dorsal columns were retrogradely labelled with horseradish peroxidase using a pellet implantation method in the thoracic dorsal columns. In the lumbosacral regions of the same animals, primary afferent fibres were labelled intra-axonally with ionophoretic application of horseradish peroxidase. Tissue containing labelled axons was prepared for light and combined light and electron microscopy. Ultrastructural examination demonstrated that slowly adapting (Type I), hair follicle, Pacinian corpuscle and group Ia muscle spindle afferents formed monosynaptic contacts with labelled cells and light microscopical analysis suggested that they also received monosynaptic input from rapidly adapting (Krause) afferents. This evidence suggests that sensory information from large-diameter cutaneous and muscle spindle afferent fibres is conveyed disynaptically via the postsynaptic dorsal column pathway to the dorsal column nuclei. Some of the input to this pathway is probably modified in the spinal cord as the majority of primary afferent boutons forming monosynaptic contacts were postsynaptic to other axon terminals. The postsynaptic dorsal column system appears to constitute a major somatosensory pathway in the cat.     

A pharmacological study of the inhibition of ventral group Ia-excited spinal interneurones

Summary In cats anaesthetized with pentobarbitone a pharmacological investigation was made of the inhibition by volleys in afferent fibres and ventral roots of physiologically identified Ia interneurones in the ventral horn.The recurrent inhibition of Ia interneurones by Renshaw cells, and the mutual inhibition between Ia interneurones, were suppressed by electrophoretic strychnine and are presumably mediated by glycine. Short latency and duration inhibitions by impulses in muscle and cutaneous afferents were also suppressed by strychnine.Electrophoretic GABA inhibited the firing of Ia interneurones and the effects of bicuculline methochloride suggested that this amino acid mediates longer latency and duration inhibition produced by afferent impulses of muscle and cutaneous origin.     

Location and morphology of dorsal spinocerebellar tract neurons that receive monosynaptic afferent input from ankle extensor muscles in cat hindlimb

1. The present experiments were carried out to investigate the morphology and somatotopic location of dorsal spinocerebellar tract (DSCT) neurons that receive monosynaptic group 1 afferent input from hindlimb ankle extensor muscles in the cat. 2. Intracellular recordings were obtained from DSCT neurons throughout the rostrocaudal extent of the L3 dorsal root entry zone of the spinal cord. DSCT neurons, physiologically identified as receiving monosynaptic group I input from the ankle extensor muscles, were injected with horseradish peroxidase (HRP) and subsequently reconstructed under the light microscope. 3. In contrast to previous HRP studies of DSCT neurons, these cells were found to have extremely extensive and complex dendritic trees, that often extend beyond the region of Clarke's column. Dendrites were found to extend into the white matter of the dorsal columns, and/or into the spinal gray matter in a ventrolateral direction. The large dendritic spread of DSCT neurons was found to occupy up to 60% or more of the cross-sectional area of Clarke's column. 4. DSCT neurons receiving monosynaptic group I input from the single functional group of ankle extensor muscles were not found to be confined within a specific transverse region of Clarke's column, in contrast to a previous proposal. Instead, these cells could be found throughout Clarke's column. 5. The present results demonstrate that DSCT neurons, physiologically identified as receiving group I muscle afferent input, exhibit dendritic trees that are considerably more extensive and morphologically complex than indicated by previous studies. In addition, the present results do not support a previous proposal of a strict somatotopic arrangement for DSCT neurons and their dendritic envelopes within Clarke's column in the transverse plane.