Renshaw Inhibition Research Articles

Immobility and F-waves: Impact on lower motor neuron excitability.

Immobility of the upper limbs has been associated with reduction of F-wave frequency. However, there are no similar studies on lower limb (LL) F-waves. We investigated the impact of LL rest on F-wave and H-reflex parameters. The LLs of 14 healthy participants were studied after 90 minutes rest. F-waves (frequency, latencies, chronodispersion, and mean amplitude) and H-reflexes (latency and recruitment curve) were investigated bilaterally. In seven participants the protocol was repeated, but the temperature of one limb was reduced. Immobility only changed F-wave latencies, which increased significantly (mean value of 2 ms, P < .01). Limb cooling did not influence results. Contrary to what occurred in cervical lower motor neurons (LMN), LL LMNs did not show a reduced F-wave response to immobility, but their latency increased significantly. This could have been due to reduced Renshaw inhibition of small LMNs, thus facilitating their response to antidromic stimulation and causing delayed late responses.

Motor units as tools to evaluate profile of human Renshaw inhibition.

To uncover the synaptic profile of Renshaw inhibition on motoneurons, we stimulated thick motor axons and recorded from voluntarily-activated motor units. Stimuli generated a direct motor response on the whole muscle and an inhibitory response in active motor units. We have estimated the profile of Renshaw inhibition indirectly using the response of motor unit discharge rates to the stimulus. We have put forward a method of extrapolation that may be used to determine genuine synaptic potentials as they develop on motoneurons. These optimized techniques can be used in research and in clinics to fully appreciate Renshaw cell function in various neurological disorders. Although Renshaw inhibition (RI) has been extensively studied for decades, its precise role in motor control is yet to be discovered. One of the main handicaps is a lack of reliable methods for studying RI in conscious human subjects. We stimulated the lowest electrical threshold motor axons (thickest axons) in the tibial nerve and analysed the stimulus-correlated changes in discharge of voluntarily recruited low-threshold single motor units (SMUs) from the soleus muscle. In total, 54 distinct SMUs from 12 subjects were analysed. Stimuli that generated only the direct motor response (M-only) on surface electromyography induced an inhibitory response in the low-threshold SMUs. Because the properties of RI had to be estimated indirectly using the background discharge rate of SMUs, its profile varied with the discharge rate of the SMU. The duration of RI was found to be inversely proportional to the discharge rate of SMUs. Using this important finding, we have developed a method of extrapolation for estimating RI as it develops on motoneurons in the spinal cord. The frequency methods indicated that the duration of RI was between 30 and 40ms depending on the background firing rate of the units, and the extrapolation indicated that RI on silent motoneurons was ∼55ms. The present study establishes a novel methodology for studying RI in human subjects and hence may serve as a tool for improving our understanding of the involvement of RI in human motor control.

Direct central action of intramuscularly injected botulinum toxin: is it harmful or beneficial?

Botulinum toxin has been clinically used for a variety of conditions ranging from cosmetic applications to post-stroke spasticity. Its potential central versus peripheral site of action has been a matter of debate, particularly as regards health and safety for the more indiscrimate cosmetic uses (Caleo & Schiavo 2009). Several animal studies indicated its direct central action after central (Akaike et al. 2013) or peripheral application of the toxin (Caleo & Schiavo, 2009). It is now becoming clear that some of its clinical benefits cannot be explained without assuming direct central effects (Filipovic et al. 2012). Most of the pain-relieving effects of the peripherally applied toxin have been interpreted as suppressing central sensitization. Its central action is plausible because botulinum toxin shares biological characteristics with tetanus toxin, which is widely recognized to have mainly central actions after peripheral application. In this issue of The Journal of Physiology, Marchant-Pauvert et al. (2013) provided physiological evidence that the toxin has direct central actions after intramuscular injection in post-stroke patients. They investigated the spinal recurrent Renshaw inhibition, which is known to be di-synaptic and would not have been affected by the injection without assuming a retrograde central effect. This paper has dual significance. First, it convincingly showed the first evidence of the direct central action in humans using a physiological technique. Secondly, their findings have an important clinical implication in treating stroke patients with botulinum neurotoxin A (BoNT-A), because of the importance of the premotor circuit involved (Renshaw cell) and because of the possibility of locally modulating the pattern of its connections. Recent clinical trials have witnessed drastic regaining of the active function of the limbs in some patients using a functional outcome measure (disability rating scale) (Marchand-Pauvert et al. 2013). In this issue of The Journal of Physiology, Marchand-Pauvert et al. (2013) show that the muscle paralysing agent BoNT-A increased the grasp power after injections into finger flexors followed by intensive rehabilitation of the treated limbs. This paradox, which has not been explained before, is now better understood by assuming a direct central action of BoNT-A, as revealed in their study. Spasticity is a syndrome of motor dysfunction caused by loss of upper motor neurons and maladaptive plasticity, involving massive synaptic reorganization at the spinal cord level. This may increase the deep tendon reflexes in late stages after stroke. Intensive rehabilitation after stroke has been the mainstay in treating the motor deficit, possibly enhancing the efficacy of indirect descending pathways from the unaffected cortices including the premotor area. However, the beneficial effect of rehabilitation is known to plateau around 6 months after stroke. One interpretation of this limitation is that abnormal spinal plasticity makes it impossible for the newly developed descending pathway to gain access to the lower motor neuron pools. It is plausible that direct spinal action of BoNT-A results not only in motor terminal degeneration but also in central synaptic reorganization after retrograde transport, so that the supraspinal descending pathways may re-establish contacts with lower motor neurons and their vicinity. Although this view needs to be tested in further animal and clinical studies, the technique of intramuscular BoNT-A injection followed by intensive rehabilitation may bring about a clinical means of central synaptic modification and a solution to the major healthcare burden to stroke survivors. Thus far, no serious adverse events have been reported in spasticity treatment with BoNT-A, despite its presumed direct central action.

Physiological effects of botulinum toxin in spasticity.

There is considerable evidence that injection of botulinum toxin (BTX) into muscles with spastic overactivity reduces resistance to passive movement in joints supplied by the injected muscles. The demonstration of improvement in active performance of the paretic limbs has been only anecdotal to date, and represents the most difficult challenge in research on BTX therapy in spastic paralysis. Data are reviewed that indicate several neurophysiological actions of BTX, other than the blocking of acetylcholine release at the neuromuscular ending: effects on the central nervous system, including retrograde axonal transport, reduced motoneuronal excitability, action on central synapses such as decreased Renshaw inhibition and increased presynaptic inhibition; action on gamma motoneuronal endings; action on most active terminals; spread of BTX to neighboring muscles; spread of BTX effects to remote muscles. Several of these neurophysiological actions are likely to contribute to improvement in active movements, as they may antagonize the primary mechanisms of functional impairment in patients with spastic paralysis: weakness, spastic cocontraction, spastic dystonia, and muscle shortening. We review the evidence for reduction of spastic cocontraction in both the injected muscle and its antagonist, and for improvement of antagonist weakness after BTX injection. The capacity of intramuscular BTX to reduce spastic dystonia and lengthen shortened muscles is also discussed based on prior literature. When injected into the more overactive of a pair of spastic antagonists around a joint, BTX should affect all the main mechanisms impairing active function around the joint.

Reciprocal and Renshaw (recurrent) inhibition are functional in man at birth

The aims were (1) to determine when in human postnatal development Group Ia reciprocal and Renshaw inhibition can be demonstrated; (2) to explore the relationship between the expression reciprocal inhibition and the disappearance of Group Ia excitatory reflexes between agonist and antagonist muscles. Studies were performed on 99 subjects, aged 1 day to 31 years, of whom 53 were neonates. A longitudinal study was also performed on 29 subjects recruited at birth and studied 3 monthly until 12 months of age. Reciprocal inhibitory and excitatory reflexes were recorded in the surface EMG of contracting biceps brachii (Bi), evoked by taps applied to the tendon of triceps brachii (Tri). Reciprocal excitatory reflexes were recorded in all but one neonate. Reciprocal inhibition was observed in 25% of neonates; evidence is provided that it was likely to have been masked by low threshold reciprocal excitation in the remaining neonates. Reciprocal inhibition was demonstrated in all subjects after 9 months of age. In four neonates there was depression of inhibition of Bi during co-contraction of Bi and Tri implying that Group Ia interneurones may be under segmental and suprasegmental control at birth. Renshaw cells, identified in human postmortem cervical spinal cord by their morphology, location and calbindin D28K immunoreactivity, were present at 11 weeks post-conceptional age (PCA) and by 35 weeks PCA had mature morphological characteristics. In four neonates reciprocal inhibitory responses in Bi disappeared when the tap to Tri evoked its own homonymous phasic stretch reflex, providing neurophysiological evidence for Renshaw inhibition of Group Ia inhibitory interneurones.

Recurrent excitation of motoneurons in the isolated spinal cord of newborn rats detected by whole-cell recording

Motoneurons in the isolated spinal cord of newborn rats (1- to 6-day-old) were visualized using infrared videomicroscopy. Whole-cell recordings were performed from the neurons under observation. Stimulation of a sciatic nerve which adjoined ventral roots elicited postsynaptic currents (PSCs) in 28 out of 88 motoneurons. When membrane potentials were changed, some PSCs reversed at around −70 mV, which was compatible with the chloride equilibrium potential calculated. Thus, they were considered to be recurrent inhibitory, namely Renshaw inhibition. On the other hand, we detected PSCs which reversed at +3.3 mV on average. They were interpreted as excitatory based on the level of the reversal potential which was similar to that of orthodromic excitatory PSCs. To determine the origin of the antidromic excitatory inputs, the effect of d-tubocurarine (10 μM) on the PSCs was examined. In three out of five motoneurons, the excitatory currents were eliminated. Therefore, it was concluded that the excitatory inputs, if not all, are mediated via the axon collaterals. Furthermore, it was found that the locations of motoneurons receiving the recurrent inhibitory and the excitatory PSCs were different in the spinal cord.

Decorrelating actions of Renshaw interneurons on the firing of spinal motoneurons within a motor nucleus: a simulation study.

A simulation of spinal motoneurons and Renshaw cells was constructed to examine possible functions of recurrent inhibition. Recurrent inhibitory feedback via Renshaw cells is known to be weak. In our model, consistent with this, motoneuron firing was only reduced by a few pulses per second. Our initial hypothesis was that Renshaw cells would suppress synchronous firings of motoneurons caused by shared, dynamic inputs. Each motoneuron received an identical pattern of noise in its input. Synchrony coefficients were defined as the average motoneuron population firing relative to the activity of selected reference motoneurons; positive coefficients resulted if the motoneuron population was particularly active at the same time the reference motoneuron was active. With or without recurrent inhibition, the motoneuron pools tended to show little if any synchronization. Recurrent inhibition was expected to reduce the synchrony even further. Instead, it reduced the variance of the synchrony coefficients, without a comparable effect on the average. This suggests-surprisingly-that both positive and negative correlations between motoneurons are suppressed by recurrent inhibition. In short, recurrent inhibition may operate as a negative feedback mechanism to decorrelate motoneurons linked by common inputs. A consequence of this decorrelation is the suppression of spectral activity that apparently arises from correlated motoneuron firings due to common excitatory drive. Without recurrent inhibition, the power spectrum of the total motoneuron pool firings showed a peak at a frequency corresponding to the largest measured firing rates of motoneurons in the pool. Recurrent inhibition either reduced or abolished this peak, presumably by minimizing the likelihood of correlated firing among pool elements. Renshaw cells may act to diminish physiological tremor, by removing oscillatory components from aggregate motoneuron activity. Recurrent inhibition also improved coherence between the aggregate motoneuron output and the common drive, at frequencies above the frequency of the "synchronous" peak. Sensitivity analyses demonstrated that the spectral effect became stronger as the duration of inhibitory synaptic conductance was shortened with either the magnitude or the spatial extent of the inhibitory conductances increased to maintain constant net inhibition. Overall, Renshaw inhibition appears to be a powerful way to adjust the dynamic behavior of a neuron population with minimal impact on its static gain.

Soleus H reflex extinction in controls and spastic patients: ordered occlusion or diffuse inhibition?

Extinction of the soleus H reflex at higher stimulus intensities is commonly attributed to retrograde conduction of action potentials in motor axons. This study was designed to gain further insight into the mechanisms underlying the extinction. The decrease of the H reflex was quantified in a group of controls and spastic patients, with and without depression of the H response by continuous tendon vibration. Response amplitudes were normalized as a percentage of the maximal M wave amplitude. Stimuli were normalized as a multiple of the M wave threshold. After normalization, the mean M recruitment curves, and similarly the fractions of motor axons activated, were equal in each group. In contrast, the mean H reflex amplitudes at the M threshold were different. The mean H reflex decrease, between 1.0 and 1.5 times the M threshold, was found to be the same fraction of the maximal H reflex amplitude in each group. The largest motor fibres, belonging to the largest motoneurones, are traditionally thought to have the lowest threshold for electrical excitation. Collision or retrograde inactivation should therefore preferentially affect the largest motoneurones, employed in only the largest H reflexes, at the lowest stimulus intensities. Our results are contrary to this hypothesis. Renshaw and/or Ib inhibition is likely to play a role in the initial decrease of the H reflex at higher stimulus intensities.

The simple frequency response of human stretch reflexes in which either short‐ or long‐latency components predominate.

1. The stretch reflexes of the human abductor digiti minimi (ADM) and biceps brachii muscles were compared using small-amplitude sinusoidal stretching at 10-50 Hz and recording the surface EMG. The stimulus was applied either to the relevant proximal phalanx or to the biceps tendon while the muscle studied was contracting; the same amplitude was used for all frequencies (range 0.5-2 mm for ADM, 0.1-1 mm for biceps). 2. As the frequency increased, the response of ADM decreased while that of biceps increased. Neither muscle showed a minimum at 20-25 Hz, as previously found for wrist muscles and attributed to an interaction between short- and long-latency components of the reflex. 3. For both muscles, the phase of the response lagged behind the stimulus by an amount which increased approximately linearly with frequency, without the gross inflexion found for wrist muscles. Such linearity would be found for a system dominated by a fixed time delay; its value sets the slope. The slope for biceps was half that for ADM. The values of reflex delay calculated from the slope of the phase plots agreed reasonably with the absolute latencies of the responses evoked by tap or ramp stimulation. Part of the difference between the muscles was due to differences in peripheral conduction time, since ADM lies more distally. Most of it, however, was due to different reflexes being involved, with biceps being predominantly controlled by short-latency pathways and ADM by long-latency pathways. 4. For both muscles, the phase lag at any given frequency was less than that expected from the reflex latency, determined from the slope of the phase plot. Thus, sensory transduction and central transmission had produced a phase advance in the reflex. The 'neural phase advance' of biceps was appreciably larger than that of ADM, and more than would be expected from the behaviour of its spindle afferents. The excess is suggested to be due to the action of Renshaw inhibition, which ADM may lack. 5. The results were substantiated by recording from single motor units in biceps. Stretching at the present amplitudes had rather little effect on the overall rhythmic behaviour, as shown by interspike interval histograms. However, cycle histograms showed that the discharge was modulated reasonably sinusoidally by the stretching, whatever its frequency (i.e. the probability of the occurrence of a spike varied over the cycle). Cyclic changes were also found in autocorrelograms and amplitude spectra of the spike trains.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinal and supraspinal mechanisms contribute to the silent period in the contracting soleus muscle after transcranial magnetic stimulation of human motor cortex

In the voluntarily activated muscle, transcranial magnetic stimulation (TMS) of motor cortex produces subsequently to the motor evoked potential (MEP) a silent period (SP) in the electromyogram. We studied the time course of soleus motoneuron (MN) pool excitability after conditioning TMS by Hoffmann reflex (HR) testing, to determine whether inaccessibility of MNs after corticospinal input contributes to the SP. Coincidently with the early part of the SP, and only in the contracting soleus, MN depression was obtained that covaried with the degree of preinnervation, and with the size of the preceding MN discharge. However, MN excitability recovered significantly prior to the end of the SP. It is concluded that in the contracting soleus spinal mechanisms (most likely Renshaw inhibition and MN afterhyperpolarization) contribute to the early part of the SP, while the late part of the SP is supraspinal (probably cortical) in origin.

Cramps: A sign of motoneurone ‘bistability’ in a human patient

In a patient suffering from severe long-lasting cramps, cramps were triggered in the triceps surae by volleys in homonymous Ia afferents (elicited by electrical stimulation or by tendon taps) and were interrupted by antidromic invasion and Renshaw inhibition of triceps surae motoneurones (evoked by a single maximal stimulation of motor axons). This result suggests that the mechanisms which generate the cramps are intrinsic to α-motoneurone somata. A similar on-off switching of a self-sustained motor discharge has been observed in the decerebrate cat and recognized to depend on ‘bistability’ of the motoneuronal membrane. We propose that the same mechanism may be at the origin of the cramp discharge.

Recurrent and reciprocal inhibition of the human monosynaptic reflex shows opposite changes following intravenous administration of acetylcarnitine

A long-latency, long-lasting increase in the recurrent inhibitory effect on the soleus monosynaptic (Hoffmann, H) reflex was induced after intravenous administration of L-acetylcarnitine, a substance known to process central cholinergic activity. This effect was paralleled by disappearance of the H reflex inhibition (functionally disinhibition) induced by stimulation of Ia afferent fibres from the tibialis anterior (reciprocal inhibition) and gastrocnemius medialis muscle. Magnitude and time course of the L-acetylcarnitine-induced effects were significantly correlated. The data suggest that (1) the L-acetylcarnitine depression of the reciprocal inhibition is mediated by excitation of Renshaw cells impinging on Ia interneurones (INs), and (2) the inhibitory effect of GM Ia afferents onto Sol is mediated by INs subjected to Renshaw inhibition. The results point to the similarity in the wiring of the 'output stage' circuit between cat and humans, and provide a method for testing this network in man.

Monosynaptic Ia excitation and recurrent inhibition from quadriceps to ankle flexors and extensors in man.

1. Ia projections and recurrent inhibition from quadriceps to tibialis anterior and soleus motoneurones were investigated in man. 2. Changes in the firing probability of individual voluntarily activated motor units were studied following electrical stimulation of the femoral nerve or quadriceps tendon tap. 3. Femoral nerve stimulation evoked an early increase in the firing probability of tibialis anterior units. This excitation was also evoked by a tendon tap, had a low threshold and its central delay was estimated to be the same as that of the homonymous monosynaptic Ia excitation. These findings strongly suggest that the femoral nerve-induced excitation is Ia in origin and mediated through a monosynaptic pathway. 4. The frequency of heteronymous Ia excitation from quadriceps was about the same to both ankle flexor and extensor units (79 and 70% respectively). 5. In 80% of both tibialis anterior and soleus units the Ia excitation was followed by a decrease in firing probability. This inhibition had a short latency and a long duration (up to 40 ms); it always appeared with the quadriceps reflex discharge and increased with it. These findings suggest that this decrease in firing probability is due to the Renshaw inhibition evoked by the quadriceps motoneurone discharge. 6. Both the Ia excitation and the following inhibition of tibialis anterior and soleus units were also observed when the stimulation was applied to the nerve of the vastus lateralis (a pure knee extensor). 7. The functional significance of these identical projections from quadriceps to both ankle flexor and extensor motoneurones is discussed with regard to the requirements of bipedal stance and gait.

Further evidence for Renshaw inhibition in man. A combined electrophysiological and pharmacological approach

Experiments involving the acute administration of a central cholinergic substance ( l-acetylcarnitine) were performed on 6 healthy subjects to obtain additional evidence that the electrophysiological method developed by Bussel and Pierrot-Deseilligny in 1977 does actually assess recurrent inhibition in man. In all the subjects, the drug further decreased the amplitude of a test H reflex (H′) following a conditioning H reflex (H1). The amount of this supplementary inhibition was found to be related to the size of H1 reflex. Experimental evidence is also presented that H′ reflex supplementary depression is not contaminated by homonymous Ib effects. It is concluded that the method effectively tests the excitability of Renshaw cells in man.

Changes in human alpha-motoneurone excitability following mechanical muscle stimuli

Short mechanical stretches given to partially activated human abductor digiti minimi muscle (ADM) evoke early (M1) and late (M2) reflex responses. Transcranial magnetic brain stimuli were used to evoke compound muscle action potentials in ADM and hence to estimate motoneuronal excitability at various times after mechanical stimuli. There was no evidence that Ia volleys produce additional facilitation in motoneurones of muscles which are already voluntarily activated. However, the inhibitory phase between M1 and M2 was associated with a reduction in size of muscle responses from brain stimuli. This may reflect reduced Ia input, polysynaptic Ia inhibition or Renshaw inhibition.

Distribution of single-axon recurrent inhibitory post-synaptic potentials in a single spinal motor nucleus in the cat.

1. The distribution of recurrent Renshaw inhibition was examined in the medial gastrocnemius motor nucleus of the cat by measurement of single-axon recurrent inhibitory post-synaptic potentials (recurrent i.p.s.p.s) in motoneurones supplying medial gastrocnemius produced by single impulses of antidromically stimulated single motor axons supplying the same muscle. 2. Stimulated motor-axon-recorded-motoneurone pairs were classified as 'close' if both contributed their axons to the same portion of the ventral roots (L7 rostral, L7 caudal or S1). Alternatively, they were classified as 'distant' if their axons were in different portions of these ventral roots. 3. Both the incidence and amplitude of 'close-pair' recurrent i.p.s.p.s were shown to be significantly larger than the corresponding values for 'distant-pair' recurrent i.p.s.p.s. 4. The results provided evidence of a strong topographic effect on the distribution of recurrent Renshaw inhibition within a single spinal motor nucleus. This finding is discussed in relation to the roles of topographic and species specificity in determining the organization of recurrent inhibition and to the partitioned distribution of monosynaptic Ia excitation in single motor nuclei.

Recurrent inhibition of cat phrenic motoneurons

These experiments were performed to re-examine the presence of a recurrent inhibitory pathway to phrenic motoneurons in cats. Following intracellular staining of 49 phrenic motoneurons with horseradish peroxidase, initial axon collaterals were demonstrated in six axons (12%). Intracellular recording and averaging of the synaptic responses evoked by stimulation of the phrenic roots with an intensity subthreshold for axons of the examined motoneurons revealed (in spinalized cats with dorsal roots cut) inhibitory postsynaptic potentials (i.p.s.p.s) in 11/28 (40%) motoneurons (amplitude, 115 +/- 69 (SD) microV; latency, 3.0 +/- 0.6 msec; duration from 12 to 25 msec). In the vicinity of the phrenic nucleus, Renshaw-like units were extracellularly recorded, which fired high-frequency bursts of action potentials following the stimulation of the phrenic roots (burst duration, 8 to 21 msec). Antidromic activation of the C5 phrenic root reduced the firing probability of fibers in the C6 root. The duration of the reduced firing probability corresponded to the duration of both the i.p.s.p.s and the Renshaw units' firing period. It is concluded that Renshaw inhibition is present in phrenic motoneurons. The inhibitory effects of this recurrent pathway may be greater than judged from the small amplitude of the i.p.s.p.s recorded in individual motoneurons, particularly when the whole phrenic pool is activated and when motoneurons are near threshold. It is suggested that one of the functions of the pathway is to control phrenic motoneurons supplying the dorsal part of the diaphragm through the C6 root when the more ventral part of the diaphragm is strongly activated.

Distribution of oligosynaptic group I input to the cat medial gastrocnemius motoneuron pool.

To characterize the oligosynaptic group I afferent input to the cat medial gastrocneumius (MG) motoneuron pool, the medial branch of the tibial nerve (MTIB: flexor digitorum and hallucis longus, popliteus, tibialis posterior and interosseous nerves), the nerves to flexor digitorum and hallucis longus (FDHL), or the nerves to the quadriceps muscles (QUAD) were stimulated at submaximal group I strength while recording intracellularly from MG motoneurons. Since previous work indicates that stimulation of these nerves at group I strength produces no significant monosynaptic Ia excitation or Renshaw inhibition of MG motoneurons, group I effects were assumed to be predominantly, though not exclusively, due to the action of Ib-fibers. Evidence supporting this assumption is presented in the following paper. MTIB, FDHL, and QUAD postsynaptic potentials (PSPs) were most commonly inhibitory. Since the MTIB, FDHL, and QUAD nerves are composed predominantly of fibers innervating muscles with extensor action, their inhibitory effect on MG motoneurons is consistent with previous findings that stimulation of Ib-afferents in nerves to extensor muscles produces di- and trisynaptic inhibition of extensor motoneurons. However, excitatory effects were observed in about one third of the motoneurons, indicating that oligosynaptic group I input is not homogeneously distributed within the MG motoneuron pool. Variations in QUAD, FDHL, and MTIB PSP pattern and amplitude were correlated with variations in the PSP pattern evoked by stimulation of the sural nerve: excitatory oligosynaptic group I PSPs generally appeared in motoneurons receiving excitatory cutaneous (sural nerve) input, whereas inhibitory PSPs generally appeared in motoneurons receiving some inhibitory cutaneous input and were largest in motoneurons receiving predominantly inhibition from the sural nerve. These variations in QUAD, FDHL, and MTIB PSP pattern and amplitude were not due to variations in resting potential and were only partly due to variations in intrinsic motoneuron properties or motoneuron "type." Our results indicate that activation of these cutaneous and group I muscle afferents can exert similar effects on the MG motoneuron pool. Moreover, the presence of a strong correlation between the distributions of cutaneous and oligosynaptic group I PSPs within a single motoneuron pool is consistent with the results of previous studies that have shown that some of the input to motoneurons from these peripheral afferents is mediated through common interneurons.

Autogenetic inhibition of extensor gamma‐motoneurones revealed by electrical stimulation of group I fibres in the cat.

Forty functionally single gamma-efferents (20-42 m/s) to the triceps surae were isolated in ventral root filaments of the decerebrated and paralysed cat in order to study the effects of group I muscle afferents on their own fusimotor neurones. All the efferents studied were spontaneously active. During splitting the continuity of the efferent fibre was preserved so that the destination of the target muscle of the efferent could be determined by antidromic stimulation of the muscle nerve using the collision block technique. Thereafter the filament was cut so that the reflex response, uncontaminated by antidromic impulse invasion, could be recorded from the central end. Sixteen of forty gamma-efferents to the triceps were inhibited by repetitive stimulation (range -3 to -40 impulses/s) of the homonymous nerve within the group I range. Raising the stimulus strength above the group II threshold produced no further increase in inhibition. Twelve of these sixteen cells were also tested by stretching the triceps; ten showed marked inhibition, and two were not influenced. In ten of the sixteen inhibited cells, the autogenetic inhibition at maximum group I stimulus strength was larger than the maximum antidromic inhibition elicited by stimulation of the remainder of the cut ventral roots L7 and S1. Since both effects were additive, it is concluded that Renshaw inhibition is at least not solely responsible for the autogenetic inhibition. Consistent with this assumption is the observation that some cells receiving electrically evoked autogenetic inhibition were not susceptible to inhibition induced by small-amplitude vibration of the triceps. Since small-amplitude vibration is known to excite most of the Ia afferents of the vibrated triceps, Ib afferents must be involved in the autogenetic fusimotor inhibition. A contribution of Ia afferents to the autogenetic inhibition (via alpha-motoneurones and Renshaw cells or via Ib inhibitory interneurones) seems likely since inhibition, induced by small-amplitude vibration, was detectable in many of the cells receiving autogenetic group I inhibition. All of these cells were susceptible to antidromic inhibition. Ten of the forty cells tested responded with tonic facilitation to the homonymous nerve stimulation. Some arguments favour the view that static gamma-motoneurones are involved in the low-threshold autogenetic inhibition. The results strongly support earlier work suggest a regulatory function of low-threshold muscle receptors on their own gamma-motoneurones.

Benzodiazepines enhance the bicuculline-sensitive part of recurrent Renshaw inhibition in the cat spinal cord

The effects of intravenous diazepam and midazolam on recurrent Renshaw inhibition of lumbar motoneurones were studied in unanaesthetized spinal cats. Both benzodiazepines enhanced the bicuculline-sensitive, late part of recurrent inhibition without affecting its strychnine-sensitive, early component. The results support the view that some Renshaw cells are GABAergic and extend the potentiating effect of benzodiazepines to a spinal GABAergic synapse that mediates postsynaptic inhibition.