Tachykinins mediate changes in spinal reflexes after activation of unmyelinated muscle afferents in the rat.

The effect of intrathecally applied tachykinin antagonist D-NicLys1, 3-Pal3, D-Cl2Phe5, Asn6, D-Trp7.9, Nle11-substance P, spantide II, on the long-term increase of spinal cord excitability after activation of unmyelinated muscle afferents was studied in decerebrate, spinalized, unanaesthetized rats. A conditioning stimulus train (1 Hz, 20 s) that activated unmyelinated fibres in the gastrocnemius muscle nerve facilitated the flexor reflex for about 1 h, which was strongly blocked by pretreatment with spantide II (3 micrograms). The present results indicate that the facilitation of the flexor reflex by conditioning stimulation of a muscle nerve is mediated by tachykinins and possibly other neuropeptides which may be released from the central terminals of these unmyelinated afferents.     

On the role of NK-2 tachykinin receptors in the mediation of spinal reflex excitability in the rat.

The effects of intrathecal administration of neurokinin A, substance P and [Tyr5, D-Trp6,8,9 Arg10]neurokinin A-(4-10) (Men 10207), a specific NK-2 receptor antagonist, on the spinal nociceptive flexor reflex were studied in decerebrate, spinalized, unanesthetized rats. Intrathecal neurokinin A and substance P facilitate the flexor reflex in a similar manner. The reflex facilitation to intrathecal neurokinin A, but not substance P, is dose-dependently blocked by pretreatment with Men 10207. The NK-2 receptor antagonist by itself facilitates the flexor reflex with a potency about 10 times less than that of neurokinin A, indicating a partial agonistic property. Reversible depression of the flexor reflex, which is not due to nonspecific spinal blockade, is observed after 700 pmol Men 10207. Further increasing the dose of Men 10207 to 7 nmol for 20 s at an intensity that activates unmyelinated (C) fibers stimulation of peripheral nerves at 1 Hz for 20 s at an intensity that activates unmyelinated (C) fibers facilitates the ipsilateral flexor reflex. The duration of the facilitation after conditioning stimulation of the cutaneous sural nerve is several minutes and about 1 h after conditioning stimulation of the gastrocnemius muscle nerves. Pretreatment with Men 10207 (70-700 pmol) has no effect on facilitation by the sural nerve conditioning stimulation, but effectively blocks the long-term reflex facilitation to the gastrocnemius nerve stimulation. The present results indicate a distinct role for NK-2 tachykinin receptors in mediation of spinal reflex excitability in the rat. Neurokinin A may be involved in the long-term increase of spinal reflex excitability after activation of unmyelinated fibers innervating muscle.     

Recurrent inhibition from motor axon collaterals of transmission in the Ia inhibitory pathway to motoneurones

1. The effects of impulses in recurrent motor axon collaterals on reflex transmission from different types of primary afferents to motoneurones were investigated in the cat by conditioning of PSPs evoked in motoneurones.

2. IPSPs evoked by volleys in large muscle spindle (Ia) afferents were effectively decreased when preceded by an antidromic stimulation of ventral roots. Some IPSPs from group II muscle afferents and low threshold cutaneous afferents were also slightly depressed, while other PSPs were unaffected.

3. The depression of the IPSPs could be evoked by antidromic volleys, which produced neither conductance changes in the motoneurones nor depolarization of Ia afferent terminals.

4. The effect on the Ia IPSPs is most likely due to post-synaptic inhibition of the Ia inhibitory interneurones, evoked through α-motor axon collaterals and Renshaw cells. The depression of some IPSPs from flexor reflex afferents is explained by a convergence of excitatory effects from these afferents on the Ia inhibitory interneurones.

5. The results indicate a selective recurrent control from motor axon collaterals of the interneurones in the reciprocal Ia inhibitory pathway to motoneurones.

     

Parallel reflex pathways from flexor muscle afferents evoking resetting and flexion enhancement during fictive locomotion and scratch in the cat

Reflex actions of muscle afferents in hindlimb flexor nerves were examined on ipsilateral motoneurone activity recorded in peripheral nerves during midbrain stimulation-evoked fictive locomotion and during fictive scratch in decerebrate cats. Trains of stimuli (15–30 shocks at 200 Hz) were delivered during the flexion phase at intensities sufficient to activate both group I and II afferents (5 times threshold, T ). In many preparations tibialis anterior (TA) nerve stimulation terminated ongoing flexion and reset the locomotor cycle to extension (19/31 experiments) while extensor digitorum longus (EDL) stimulation increased and prolonged the ongoing flexor phase activity (20/33 preparations). The effects of sartorius, iliopsoas and peroneus longus muscle afferent stimulation were qualitatively similar to those of EDL nerve. Resetting to extension was seen only with higher intensity stimulation (5 T ) while ongoing flexor activity was often enhanced at group I intensity (2 T ) stimulation. The effects of flexor nerve stimulation were qualitatively similar during fictive scratch. Reflex reversals were consistently observed in some fictive locomotor preparations. In those cases, EDL stimulation produced a resetting to extension and TA stimulation prolonged the ongoing flexion phase. Occasionally reflex reversals occurred spontaneously during only one of several stimulus presentations. The variable and opposite actions of flexor afferents on the locomotor step cycle indicate the existence of parallel spinal reflex pathways. A hypothetical organization of reflex pathways from flexor muscle afferents to the spinal pattern generator networks with competing actions of group I and group II afferents on the flexor and extensor portions of this central circuitry is proposed.     

Development in neonatal rats of the sensory resetting of the locomotor rhythm induced by NMDA and 5-HT

 Developmental changes in the effects of quadriceps (Q) nerve stimulation on the locomotor rhythm induced by a mixture of N-methyl-d-aspartic acid and 5-hydroxytryptamine were examined using in vitro preparations from neonatal rats at postnatal days (P) 1–6. The effects of such stimulation on the rhythm were dependent both on stimulus strength and on the age of the animal. Low-intensity stimulation (≤3.0×T, where T=threshold for the monosynaptic reflex) during the flexor phase reset the rhythm via a prolongation of the flexor burst in most rats at P1–3, but via flexor burst truncation at P4–6. At any age, low-intensity stimulation during the extensor phase had no consistent effect on the ongoing rhythm. Activation of muscle afferents evoked via isometric contraction of the Q muscle caused effects similar to those obtained on low-intensity electrical stimulation in all age groups. In all age groups, high-intensity stimulation (≥5.0×T) caused resetting when delivered during the flexor phase via a prolongation of the flexor burst and during the extensor phase via a truncation of the extensor burst. These results suggest that the type of resetting evoked from low-threshold muscle afferents changes drastically during postnatal week1, while effects evoked from high-threshold afferents remain unchanged. Received: 13 May 1996 / Accepted: 17 September 1996     

Neural mechanisms underlying the clasp-knife reflex in the cat. II. Stretch-sensitive muscular-free nerve endings

1. The goal of this study was to determine the contribution of muscular free nerve endings to the clasp-knife reflex by comparing their response properties and reflex actions to the clasp-knife reflex. 2. The responses of single muscle afferents were examined in anesthetized cats using stretch and isometric contraction of ankle extensor muscles identical to those that evoked clasp-knife inhibition in decerebrated and dorsal spinal-hemisectioned cats. 3. Fifty-three stretch-sensitive mechanoreceptor afferents were identified as free nerve ending afferents based on their conduction velocities, location within the muscle, uniformity of response, and dissimilarity to other muscle proprioceptors. The afferent conduction velocities were in both the group III (56%) and group II (44%) range, including five fast-conducting group II afferents (greater than 55 m/s). 4. The stretch response of stretch-sensitive, free nerve endings (SSFNEs) showed several characteristic features: 1) afferents were excited only by large stretches that produced significant passive force; 2) afferent activity began after a brief delay and exhibited segmentation of discharge during ramp stretch, a maximum at the end of ramp stretch, and rapid and complete decay during static stretch, and 3) afferent response adapted to repeated stretches. These properties match those of clasp-knife inhibition described in the companion paper, except that the SSFNE segmentation and maximum were more pronounced and their decay during maintained stretch was more rapid. 5. Isometric contraction produced by electrical stimulation of the muscle nerve, which induced force-evoked inhibition in decerebrated and dorsal hemisectioned cats, also consistently excited SSFNEs. Stretch evoked greater excitation than contraction, indicating that both length and force contribute to SSFNE activity. 6. Stimulation of free nerve endings by squeezing the achilles tendon in cats exhibiting the clasp-knife reflex evoked powerful, homonymous inhibition and a flexion-withdrawal pattern of reflex action--that is, inhibition of extensor and excitation of flexor muscles throughout the hindlimb, which parallels the spatial divergence of the clasp-knife reflex. 7. Intrathecal application of capsaicin, which preferentially blocks the reflex actions of small afferent fibers, blocked clasp-knife inhibition in decerebrated, dorsal hemisectioned cats. 8. The similarities between the reflex actions and response properties of SSFNEs and the properties of the clasp-knife reflex suggest that SSFNEs mediate clasp-knife inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cutaneous nerve-evoked cholinergic inhibition of monosynaptic reflex in the neonatal rat spinal cord: involvement on M2 receptors and tachykininergic primary afferents.

The mechanisms of a cutaneous nerve-evoked inhibition of monosynaptic reflex were investigated in an isolated spinal cord-peripheral nerve preparation of the neonatal rat. Conditioning stimulation of the saphenous nerve, with five pulses at 50 Hz and a strength sufficient to activate C fibers, evoked an inhibition lasting about 20 s of the monosynaptic reflex that was elicited by stimulation of the nerve branch to quadriceps femoris muscle and recorded from the L3 ventral root. This inhibition of monosynaptic reflex was potentiated by an anticholinesterase, edrophonium, and mostly blocked by atropine. Application of acetylcholine, muscarine, bethanechol, carbachol, arecoline and oxotremorine induced an inhibition of monosynaptic reflex. From the effects of muscarinic antagonists, pirenzepine, AF-DX 116, and 4-diphenylacetoxy-N-methylpiperidine on the agonist-evoked and primary afferent-evoked inhibition of monosynaptic reflex it was concluded that the muscarinic receptors involved in the cutaneous nerve-evoked inhibition of monosynaptic reflex are of M2 type. When monosynaptic reflexes were evoked by two successive stimuli with intervals of 15 ms to 1 s, the second response was smaller than the first. This depression of monosynaptic reflex became less pronounced when the reflex was reduced by application of oxotremorine or arecoline or by conditioning stimulation of primary afferents, suggesting that the inhibition of monosynaptic reflex is presynaptic in nature. The late phase of the cutaneous nerve-evoked inhibition of monosynaptic reflex (5-20 s after conditioning stimulation) was markedly depressed by a tachykinin antagonist, spantide. Perfusion of the spinal cord with capsaicin (1 microM) for 1 h also abolished the late phase of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tonic suppression of reflex transmission in low spinal cats

Summary Transmission in various spinal hindlimb reflex pathways arising from muscle, cutaneous and joint afferents, was investigated in acute low spinal (Th10) cats before and after lesions at more caudal levels in the lumbar segments. Lesions of the ipsilateral dorsolateral funiculus (DLF) resulted in increased mono- and polysynaptic ventral root discharges. With conditioning of monosynaptic reflexes it was demonstrated that the DLF lesion enhanced transmission in reflex pathways from group II and III muscle afferents. The DLF lesion also resulted in increased dorsal root potentials from cutaneous, joint and group III muscle afferents. These reflex enhancements could not be obtained with lesions rostral to L2, but developed with lesions in L2 and to some extent in L3, but no further effect was obtained by adding lesions caudal to L3. Ventral extension of the DLF lesion gave hardly any increase of reflex transmission. It is postulated that the investigated reflex pathways may be tonically inhibited in the acute low spinal state by propriospinal neurones with cell bodies in the L2–L3 segments and with axons descending in the dorsolateral funiculus.Abbreviations LF Lateral funiculus - DLF dorsolateral funiculus - FRA flexor reflex afferents - DRP dorsal root potential - PAD primary afferent depolarization - PBSt Nerves: posterior biceps and semitendinosus - ABSm anterior biceps and semimembranosus - Sur sural - G-S gastrocnemius and soleus - Pl plantaris - FDHL flexor digitorum and hallucis longus - j posterior knee joint - DP deep peroneus - SP superficial peroneus - Sart sartorius - Q quadriceps     

D-Arg1, D-Trp79, Leu11-substance P (spantide) does not antagonize substance P-induced hyperexcitability of the nociceptive flexion withdrawal reflex in the rat

The effect of D-Arg^-1, D-Trp^7,9, Leu¹¹-substance P (SP) (spantide), a putative SP antagonist, on SP-induced facilitation of the flexion reflex was examined. The drugs were injected intrathecally (i.t.) in decerebrate, spinalized, unanaesthetized rats. Substance P (10 ng) caused an increase in reflex magnitude for about 5 min. Spantide (10 ng and 100 ng) also caused a facilitation of the reflex that was similar to SP. Spantide (10 ng) plus SP (10 ng) also had a similar excitatory effect. One microgramme of spantide totally blocked the flexion reflex, which could not be reversed by SP, L-glutamate, L-aspartate or naloxone. It is concluded that spantide does not have an antagonistic effect on SP-induced changes in spinal reflex excitability. Some of the effects of i.t. spantide observed in behavioural studies may be due to a non-specific spinai motor block. It is suggested that the flexion reflex in the decerebrate, spinalized rat is a useful physiological model in studies of the effects of algesic and analgesic drugs at spinal level.     

Increase in group II excitation from ankle muscles to thigh motoneurones during human standing

In standing subjects, we investigated the excitation of quadriceps (Q) motoneurones by muscle afferents from tibialis anterior (TA) and the excitation of semitendinosus (ST) motoneurones by muscle afferents from gastrocnemius medialis (GM). Standing with a backward lean stretches the anterior muscle pair (TA and Q) and they must be cocontracted to maintain balance. Equally, forward lean stretches the posterior muscle pair (GM and ST) and they must be cocontracted. We used these conditions of enhanced lean to increase the influence of γ static motoneurones on muscle spindle afferents, which enhances the background input from these afferents to extrafusal motoneurones. The effects of the conditioning volleys on motoneurone excitability was estimated using the modulation of the on-going rectified EMG and of the H reflex. Stimulation of afferents from TA in the deep peroneal nerve at 1.5–2 × MT (motor threshold) evoked early group I and late group II excitation of Q motoneurones. Stimulation of afferents in the GM nerve at 1.3–1.8 MT evoked only late group II excitation of ST motoneurones. The late excitation produced by the group II afferents was significantly greater when subjects were standing and leaning than when they voluntarily cocontracted the same muscle pairs at the same levels of activation. The early effect produced by the group I afferents was unchanged. We propose that this increase in excitation by group II afferents reflects a posture-related withdrawal of a tonic inhibition that is exerted by descending noradrenergic control and is specific to the synaptic actions of group II afferents.     

Contribution of group III and IV muscle afferents to multisensorial spinal motor control in cats

The contribution of group III and IV muscle afferents to multisensorial segmental reflex pathways was investigated by testing for spatial facilitation between these afferents and non-nociceptive segmental afferents from skin, muscles and joints on postsynaptic potentials (PSPs) in alpha-motoneurones recorded in anaemically decapitated high spinal cats. Group III and IV muscle afferents were activated by intraarterial injection of potassium chloride (320 mM) or bradykinin triacetate (81 microM). Skin, joint and group I-II muscle afferents were stimulated by graded electrical stimulation of various nerves. Conditioning by stimulation of group III and IV muscle afferents spatially facilitated the transmission in segmental reflex pathways from low- to medium-threshold cutaneous and joint afferents as well as from lb and group II muscle afferents. Both excitatory and inhibitory pathways from these afferents were facilitated. Monosynaptic excitation and disynaptic antagonistic inhibition from group Ia afferents remained unaffected. It is concluded that the spatial facilitation observed between group III and IV muscle afferents and the other afferents indicate a convergence from group III and IV muscle afferents and the other afferents on common interneurones in segmental flexor reflex pathways. Under physiological conditions they thus contribute to the multisensorial feedback of the flexor reflex pathways. Pathophysiologically, the observed convergence may aggravate muscle weakness and atrophy of muscles induced by group III and IV muscle afferents.     

Medium-latency reflex response elicited from the flexor carpi radialis by radial nerve stimulation

The H reflex obtained from the flexor carpi radialis muscle by median nerve stimulation is a well-known monosynaptic reflex. However, the origin of the late responses is still contentious. Radial nerve stimulation was performed through the spiral groove, and EMG recording was obtained from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. An M response followed by an F response was achieved from the ECR by radial nerve stimulation; the antagonistic FCR muscle elicited a late response. A total of 25 cases were included in this study. In 22 of these cases, a response with a latency of 40.97 ± 5.35 ms was obtained from the FCR by radial nerve stimulation. When extension of the hand was restricted, the response disappeared in five of nine cases. Application of cold markedly suppressed the response and prolonged the latency of the FCR medium-latency reflex response (FCR-MLR). Oral tizanidine considerably suppressed the FCR-MLR response. Two out of eight cases did not exhibit any response. No response could be recorded from a patient with complete amputation of the right hand. The FCR-MLR is the reflex caused by stretching of the FCR muscle from radial nerve stimulation, and it is greatly influenced by group II afferents.     

Reflex pathways from group II muscle afferents

The interneuronally mediated reflex actions evoked by electrical stimulation of group II muscle afferents in low spinal cats have been reinvestigated with intracellular recording with motoneurones to knee flexors and ankle extensors. The results of Eccles and Lundberg (1959) have been confirmed and extended. There was wide convergence from flexors and extensors of group II excitation to flexor and group II inhibition to extensor motoneurones. Some quantitative differences in the effect from the different nerves are described. Latency measurements suggest that the minimal linkage is disynaptic in the excitatory interneuronal pathways and trisynaptic in the inhibitory pathways. Disynaptic group II EPSPs were found in 14% of the ankle extensor motoneurones but were much more common in unanaesthetized high spinal cats (Wilson and Kato 1965). From these results and corresponding ones on flexors (Holmqvist and Lundberg 1961) it is postulated that secondary afferents in addition to the weak monosynaptic connexions (Kirkwood and Sears 1975) have disynaptic excitatory pathways and trisynaptic inhibitory pathways to both flexor and extensor motoneurones. It is proposed that the group II actions of the flexor reflex pattern characterizing the anaesthetized low spinal cat are due to suppression of the inhibitory pathway to flexor motoneurones and the excitatory pathway to extensor motoneurones. In some ankle extensor motoneurones the disynaptic group II EPSPs occurred in combination with IPSPs from the FRA (including group II and III muscle afferents). The possibility is considered that these group II EPSPs are mediated by an interneuronal group II pathway with little or no input from group III muscle afferents but probably from extramuscular receptors. In other ankle extensor motoneurones group II EPSPs were combined with EPSPs from group III muscle afferents, cutaneous afferents and joint afferents. It is postulated that these group II EPSPs are mediated by an interneuronal pathway from the FRA which also supply interneuronal pathways giving inhibition to extensor or/and flexor motoneurones and excitation to flexors as postulated by Eccles and Lundberg (1959) and Holmqvist and Lundberg (1961).     

Spinal substance P and N-methyl-D-aspartate receptors are coactivated in the induction of central sensitization of the nociceptive flexor reflex.

We have studied the effects and interactions of the neurokinin-1 receptor antagonist CP-96,345 and the N-methyl-D-aspartate receptor/channel blocker MK-801, both applied intravenously, on the flexor reflex and on the facilitation of the flexor reflex by conditioning stimulation of cutaneous C-afferents in decerebrate, spinalized, unanesthetized rats. The flexor reflex was evoked by subcutaneous electrical stimuli applied to the sural nerve innervation area 1/min at an intensity that activated C-fibers and was recorded as electromyogram from the ipsilateral hamstring muscles. The magnitude of the baseline flexor reflex was usually highly stable in the course of the experiments without experimental manipulations. The same stimulus was used as a conditioning train (0.9 Hz, 20 shocks) and caused a brief facilitation of the flexor reflex, which was maximal 0.5 and 1 min after stimulation (255.1 +/- 23.6% over baseline). During the course of the conditioning stimulus train, the reflex magnitude was gradually increased (wind-up). MK-801 (0.1 and 0.5 mg/kg) consistently depressed the polysynaptic flexor reflex. At a dose of 0.5 mg/kg, but not 0.1 mg/kg, MK-801 reduced the wind-up and blocked the facilitation of the flexor reflex induced by the conditioning stimulus by 90%. The facilitatory effect of 7 pmol intrathecal substance P was also partially reduced by MK-801. CP 96,345 (1 and 3 mg/kg) did not depress the flexor reflex, but dose-dependently antagonized reflex facilitation by the conditioning stimulus train, similarly to its antagonism of intrathecally applied 7 pmol substance P-induced facilitation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Convergence of nociceptive and non-nociceptive inputs onto spinal reflex pathways to the tibialis anterior muscle in humans

The interaction of low-threshold mechanoreceptive and nociceptive inputs onto spinal neurones probably plays a major role in the pathophysiology of the clinical sign of allodynia. This phenomenon was investigated by modulation of the early component of the flexor reflex (FR) in the tibialis anterior (TA) muscle, elicited by electrical stimulation of the medial plantar nerve at the sole of the foot, by homotopically applied painful heat in humans. This early reflex with an electrical threshold of 2.7-fold the detection threshold and a mean afferent conduction velocity of 49 m s^?1 is a non-nociceptive FR. When applying conditioning painful heat (46 °C) to the sole of the foot this reflex was significantly increased by a factor of 3.4 (non-painful electrical stimuli; n = 5) and 2.0 (painful electrical stimuli; n = 11). The onset latencies were significantly shortened from 74.2 to 64.0 ms and 69.6 to 63.7 ms, respectively. A late nociceptive FR was also facilitated. While the Hoffmann reflex (HR) in the TA muscle was nearly abolished by painful heat, the HR in the soleus (SO) muscle remained unchanged. These data suggest a convergence of low-threshold mechanoreceptive and nociceptive inputs onto spinal reflex pathways in humans, probably at an interneuronal level in humans.     

Properties and distribution of peripherally evoked presynaptic hyperpolarization in cat lumbar spinal cord

1. The action of peripheral nerve volleys on the polarization of presynaptic terminals of inactive sensory fibres in cat lumbar spinal cord has been investigated by recording (a) the dorsal root potential (DRP), (b) intracellular changes in polarization of single preterminal axons (PAD or PAH), and (c) changes in excitability of populations of preterminal axons.2. Presynaptic hyperpolarization (positive DRP-PAH) can be evoked by stimulation of muscle group III afferents as well as by volleys in cutaneous Abeta, Adelta and C afferents. These volleys can also produce presynaptic depolarization (negative DRP-PAD).3. The positive DRP is observed in the decerebrate state and increases in amplitude following spinalization.4. Picrotoxin blocks the positive DRP at the same dosages required to block the negative DRP. Test negative DRPs are depressed during a conditioning positive DRP. These results are used to support earlier suggestions that the positive DRP results from inhibition of interneurones mediating the negative DRP.5. Trains of group III stimuli at 20/sec evoke a steady positive DRP. Trains of the same intensity at 200/sec evoke a phasic negative DRP. This frequency dependence is observed for PAD and PAH in single sensory axons.6. The DRPs recorded from different dorsal root filaments in response to a given stimulus vary widely in the ratio of negative to positive DRP.7. Intracellular recording from single axons reveals that the same stimuli evoke widely varying ratios of PAD and PAH.8. Stimulation of FRA evokes PAH > PAD in PBST group I afferents, PAD > PAH in sural A fibres and intermediate effects in G-S group I units.9. It is suggested that activation of flexor reflex afferents may selectively potentiate the synaptic efficacy of large muscle afferents mediating the flexor reflex rather than large skin afferents or large afferents from extensor muscles.     

Modelling spinal circuitry involved in locomotor pattern generation: insights from the effects of afferent stimulation

A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-centre rhythm generator (RG) and pattern formation (PF) networks has been developed from observations obtained during fictive locomotion in decerebrate cats. Sensory afferents have been incorporated in the model to study the effects of afferent stimulation on locomotor phase switching and step cycle period and on the firing patterns of flexor and extensor motoneurones. Here we show that this CPG structure can be integrated with reflex circuits to reproduce the reorganization of group I reflex pathways occurring during locomotion. During the extensor phase of fictive locomotion, activation of extensor muscle group I afferents increases extensor motoneurone activity and prolongs the extensor phase. This extensor phase prolongation may occur with or without a resetting of the locomotor cycle, which (according to the model) depends on the degree to which sensory input affects the RG and PF circuits, respectively. The same stimulation delivered during flexion produces a temporary resetting to extension without changing the timing of following locomotor cycles. The model reproduces this behaviour by suggesting that this sensory input influences the PF network without affecting the RG. The model also suggests that the different effects of flexor muscle nerve afferent stimulation observed experimentally (phase prolongation versus resetting) result from opposing influences of flexor group I and II afferents on the PF and RG circuits controlling the activity of flexor and extensor motoneurones. The results of modelling provide insights into proprioceptive control of locomotion.     

Flexor reflex afferents reset the step cycle during fictive locomotion in the cat

 The generation of locomotor-like spinal rhythms has been proposed to involve two neural centres with mutual reciprocal inhibition (Graham Brown’s ”half-centre” hypothesis). Much later a particular set of segmental flexor reflex pathways were described as being organized in accordance with this half-centre hypothesis. As these pathways became operative following injection of monoaminoxidase inhibitors and l-3,4-dihydroxyphenylalanine (l-dopa), i.e. under the same conditions under which a spontaneous locomotor activity may develop, it was assumed that these particular pathways and spinal rhythm generators involve the same neuronal networks. In order to give further evidence to this hypothesis, we investigated whether short trains to ”flexor reflex afferents” (FRA) reset the spinal locomotor rhythm, i.e. shorten or lengthen the stimulated cycle after which the regular rhythm is resumed with step cycles of the original duration. The experiments were performed in anaemically decapitated, high-spinal curarized cats. A steady locomotor rhythm was induced by injection of nialamide and l-dopa and the influence of electrical stimulation (trains of 50–1000 ms) of FRA (joint, cutaneous, and group II and III muscle afferents) onto this rhythm was tested. Stimulation of FRA induced a clear resetting of the locomotor rhythm, which was mainly characterized by a flexion reflex pattern: during the extension phase the extensor activity was interrupted and a flexion phase was initiated; during the late flexion phase mainly a prolongation of that phase with a variable change of the following extension phase was induced. In addition to this prevailing pattern, stimulation of some nerves (in particular nerves to more distal extensors and the sural nerve) could often prolong extension, when stimulated during the late extension, or terminate the flexor burst and initiate a new extension phase, when stimulated during the late flexion phase. This pattern is probably due to the concomitant stimulation of group I afferents in the case of the muscle nerves and to separate non-FRA pathways in the case of the sural nerve. The results demonstrate that the interneurones of the FRA pathways, which are operative during l-dopa-induced locomotion in spinal animals, can be considered as neuronal elements of the rhythm-generating network for locomotion. Received: 25 June 1996 / Accepted: 27 April 1998     

post-synaptic excitation and inhibition from primary afferents in neurones of the spinocervical tract

1. Intra- and extracellular recordings were made from cells of the spinocervical tract in the lumbosacral spinal cord. A convergence of monosynaptic excitatory post-synaptic potentials (EPSPs) and disynaptic inhibitory post-synaptic potentials (IPSPs) was a general pattern of effects from the low threshold cutaneous fibres. Unitary IPSPs, probably mediated via the same disynaptic path, were evoked by light touch of hairs, which was also the adequate stimulus for exciting the cells. The receptive field for unitary IPSPs was closely related to the excitatory receptive field but was eccentric, not of a surround type.

2. EPSPs, IPSPs, or both, were evoked from the flexor reflex afferents in the great majority of neurones. Disynaptic IPSPs may be evoked from the interosseous nerve. No effects were produced by volleys in group I muscle afferents.

3. It is suggested, on the basis of the spatial organization of the excitatory and inhibitory receptive skin fields, that the spinocervical tract may give information regarding the direction of tactile stimuli.

     

Excitatory actions of mushroom poison (acromelic acid) on unmyelinated muscular afferents in the rat

Ingestion of a poisonous mushroom, Clitocybe acromelalga, results in strong and long-lasting allodynia, burning pain, redness and swelling in the periphery of the body. Acromelic acid (ACRO), a kainate analogue isolated from the mushroom, is assumed to be involved in the poisoning. ACRO has two isomers, ACRO-A and ACRO-B. The potency of ACRO-A is a million times higher than that of ACRO-B for induction of allodynia when intrathecally administered in mice. The effect of ACRO on the primary afferents of somatic tissues remains largely unknown. The aim of the present study was to examine the effect of ACRO-A on the response behavior of unmyelinated afferents in the skeletal muscle. For this purpose single fiber recordings of C-afferents were made from rat extensor digitorum longus (EDL) muscle-common peroneal nerve preparations in vitro. Intramuscular injections of ACRO-A at three different concentrations (10⁻¹², 10⁻¹⁰ and 10⁻⁸ M, 5 μl over 5 s) near the receptive field in the EDL muscle elicited excitation of C-afferents (12%, 50% and 44%, respectively). ACRO-A at the concentration of 10⁻¹⁰ M induced the strongest excitation. The incidence of ACRO-A responsive fibers at the concentration of 10⁻¹⁰ and 10⁻⁸ M was significantly higher than that at 10⁻¹² M. The responses to mechanical and heat stimulations did not differ between ACRO-A sensitive and insensitive fibers. These results clearly demonstrated the powerful excitatory action of ACRO-A on mechanosensitive unmyelinated afferents in the rat skeletal muscle.