Posterior Biceps-semitendinosus Research Articles

Direct evidence for decreased presynaptic inhibition evoked by PBSt group I muscle afferents after chronic SCI and recovery with step-training in rats.

Presynaptic inhibition is modulated by supraspinal centres and primary afferents in order to filter sensory information, adjust spinal reflex excitability, and ensure smooth movement. After spinal cord injury (SCI), the supraspinal control of primary afferent depolarization (PAD) interneurons is disengaged, suggesting an increased role for sensory afferents. While increased H-reflex excitability in spastic individuals indicates a possible decrease in presynaptic inhibition, it remains unclear whether a decrease in sensory-evoked PAD contributes to this effect. We investigated whether the PAD evoked by hindlimb afferents contributes to the change in presynaptic inhibition of the H-reflex in a decerebrated rat preparation. We found that chronic SCI decreases presynaptic inhibition of the plantar H-reflex through a reduction in PAD evoked by posterior biceps-semitendinosus (PBSt) muscle group I afferents. We further found that step-training restored presynaptic inhibition of the plantar H-reflex evoked by PBSt, suggesting the presence of activity-dependent plasticity of PAD pathways activated by flexor muscle group I afferents. Spinal cord injury (SCI) results in the disruption of supraspinal control of spinal networks and an increase in the relative influence of afferent feedback to sublesional neural networks, both of which contribute to enhancing spinal reflex excitability. Hyperreflexia occurs in ∼75% of individuals with a chronic SCI and critically hinders functional recovery and quality of life. It is suggested that it results from an increase in motoneuronal excitability and a decrease in presynaptic and postsynaptic inhibitory mechanisms. In contrast, locomotor training decreases hyperreflexia by restoring presynaptic inhibition. Primary afferent depolarization (PAD) is a powerful presynaptic inhibitory mechanism that selectively gates primary afferent transmission to spinal neurons to adjust reflex excitability and ensure smooth movement. However, the effect of chronic SCI and step-training on the reorganization of presynaptic inhibition evoked by hindlimb afferents, and the contribution of PAD has never been demonstrated. The objective of this study is to directly measure changes in presynaptic inhibition through dorsal root potentials (DRPs) and its association with plantar H-reflex inhibition. We provide direct evidence that H-reflex hyperexcitability is associated with a decrease in transmission of PAD pathways activated by posterior biceps-semitendinosus (PBSt) afferents after chronic SCI. More precisely, we illustrate that the pattern of inhibition evoked by PBSt group I muscle afferents onto both L4-DRPs and plantar H-reflexes evoked by the distal tibial nerve is impaired after chronic SCI. These changes are not observed in step-trained animals, suggesting a role for activity-dependent plasticity to regulate PAD pathways activated by flexor muscle group I afferents.

Facilitation of antagonist motor output through short-latency sensory pathways during postnatal development in the mouse

Reciprocal inhibition of motor neurons via Ia inhibitory interneurons recruited by stimulation of proprioceptive afferents supplying antagonist muscles has been well described. Changes in the efficacy of inhibition, and sometimes even a switch from inhibition to facilitation, have been reported in the literature after disruption of descending pathways. We sought to test whether such facilitation could be expressed in normal animals by evaluating the presence of facilitation in acute preparations from uninjured animals. Using an isolated spinal cord preparation from neonatal mice, changes in the monosynaptic stretch reflex response in knee flexor motor neurons (posterior biceps semitendinosus; PBST) were monitored following conditioning stimulation of proprioceptive sensory afferents in other muscle nerves. As expected for reciprocal inhibition, conditioning by stimulation of quadriceps (knee extensors and PBST antagonists) sensory afferents resulted in inhibition of the stretch reflex response. Facilitation, however, of the stretch reflex response by quadriceps conditioning stimulation was observed when the glycinergic reciprocal inhibitory pathway was blocked by application of strychnine. Facilitation was elicited by low-threshold proprioceptive afferents and occurred at latencies consistent with a disynaptic circuit. The magnitude of facilitation was larger at birth than at one week postnatal. Our results also suggest reciprocal facilitation is restricted to antagonist muscle pairs, as facilitation of PBST responses was not observed when conditioned with the obturator nerve supplying the adductor muscles. Overall, these data suggest the efficacy of facilitation is modulated during the first postnatal week, while the specificity of facilitation is already established by birth.

Long lasting activity of nociceptive muscular afferents facilitates bilateral flexion reflex pattern in the feline spinal cord

Chronic muscular limb pain requires the adoption of motor patterns distinct from the classic ipsilateral flexion, crossed extension and corresponding reciprocal inhibitions to acute exteroceptive stimulation. Using selective chemical activation of group III/IV afferents in gastrocnemius-soleus (GS) muscles we investigated bilaterally their reflex responses conditioned by (a) acute ‘myositis’ induced by intramuscular carrageenan; and (b) sub-acute ‘myositis’ induced by infusion of complete Freund's adjuvant (CFA). Reflex transmission was detected by monosynaptic testing and c-fos staining used to identify increased neuronal activity. In all control experiments with chemical stimulation of group III/IV afferents, ipsilateral responses conformed to the flexor reflex pattern. However, the expected contralateral facilitation of GS motoneurones occurred in fewer than 50% trials while only 9% of trials induced contralateral inhibition of flexor posterior-biceps-semitendinosus (PBSt) motoneurones. During carrageenan acute myositis contralateral PBSt was transiently facilitated by selective activation of group III/IV afferents. During CFA-induced myositis, contralateral only inhibition of GS motoneurones occurred instead of any facilitation, while bidirectionally a crossed facilitation of PBST dominated. These reflex changes were mirrored in an enhanced number of neurones with enhanced c-fos expression. Muscle pain, particularly if chronically persistent, requires another behavioural response pattern than acute exteroceptive pain.

Spinal motor actions of the μ-opioid receptor agonist DAMGO in the cat

For further evaluation of opioidergic spinal motor functions the action of the μ-opioid receptor agonist DAMGO was tested on transmission in different non-nociceptive and nociceptive spinal reflex pathways from flexor reflex afferents (FRA), and in non-FRA reflex pathways in spinal cats. The action of DAMGO was complex, not following a simple pattern with selective depression of nociceptive pathways compared to non-nociceptive ones. Monosynaptic reflexes of the flexor posterior biceps semitendinosus (PBSt) and transmission in nociceptive as well as non-nociceptive excitatory FRA pathways to PBSt were depressed, while the specific excitatory nociceptive non-FRA pathway from the central foot pad to foot extensors was mainly not depressed but rather facilitated by DAMGO. DAMGO caused a facilitation of monosynaptic reflexes to the extensor gastrocnemius soleus (GS) and partly a reversal of inhibitory to excitatory conditioning effects from cutaneous afferents to GS. FRA interneurones could show either an increase or a cessation of their spontaneous activity, but responsiveness to nociceptive and non-nociceptive afferent activation was blocked by DAMGO. The main DAMGO action is generated via interneuronal systems rather than on motoneurones themselves. The results indicate that opioidergic spinal functions are extensively involved in spinal motor control exceeding a mere suppression of nociceptive motor withdrawal reactions.

System identification of muscle–joint interactions of the cat hind limb during locomotion

Neurophysiological experiments in walking cats have shown that a number of neural control mechanisms are involved in regulating the movements of the hind legs during locomotion. It is experimentally hard to isolate individual mechanisms without disrupting the natural walking pattern and we therefore introduce a different approach where we use a model to identify what control is necessary to maintain stability in the musculo-skeletal system. We developed a computer simulation model of the cat hind legs in which the movements of each leg are produced by eight limb muscles whose activations follow a centrally generated pattern with no proprioceptive feedback. All linear transfer functions, from each muscle activation to each joint angle, were identified using the response of the joint angle to an impulse in the muscle activation at 65 postures of the leg covering the entire step cycle. We analyzed the sensitivity and stability of each muscle action on the joint angles by studying the gain and pole plots of these transfer functions. We found that the actions of most of the hindlimb muscles display inherent stability during stepping, even without the involvement of any proprioceptive feedback mechanisms, and that those musculo-skeletal systems are acting in a critically damped manner, enabling them to react quickly without unnecessary oscillations. We also found that during the late swing, the activity of the posterior biceps/semitendinosus (PB/ST) muscles causes the joints to be unstable. In addition, vastus lateralis (VL), tibialis anterior (TA) and sartorius (SAT) muscle-joint systems were found to be unstable during the late stance phase, and we conclude that those muscles require neuronal feedback to maintain stable stepping, especially during late swing and late stance phases. Moreover, we could see a clear distinction in the pole distribution (along the step cycle) for the systems related to the ankle joint from that of the other two joints, hip or knee. A similar pattern, i.e., a pattern in which the poles were scattered over the s-plane with no clear clustering according to the phase of the leg position, could be seen in the systems related to soleus (SOL) and TA muscles which would indicate that these muscles depend on neural control mechanisms, which may involve supraspinal structures, over the whole step cycle.

Monosynaptic reflexes, c-fos expression, and NADPH-diaphorase activity in the cat spinal cord: Changes induced by chronic muscle inflammation

Effects of long-term (9 days) experimental unilateral inflammation in the mm. gastrocnemius-soleus (GS), induced by injection of Freund’s complete adjuvant, namely modulation of posterior biceps-semitendinosus (PBSt) monosynaptic reflexes (MSRs), which was induced by chemical activation of high-threshold (groups III and I) muscle afferents, and changes in c-fos expression and NADPH-diaphorase (d) reactivity in the lumbosacral spinal cord, were studied in anemically decapitated and highly (at the C1) spinalized cats. The mean amplitude of the MSRs on the pretreated side did not differ significantly from that on the opposite side. In adjuvant-injected cats, ipsilateral stimulation of nociceptive muscle afferents by KCl injection induced the bilateral enhancement of flexor reflexes. Significant bilateral increases in the mean number of Fos-immunoreactive (Fos-IR) neurons within the L6, L7, and S1 segments (157.5 ± 12.7, 201 ± 18.5, and 205 ± ± 18.6 per section; P < 0.05) were also found in adjuvant-injected cats. A lot of Fos-IR neurons was observed in the marginal zone (lamina I) and the neck of the dorsal horn (laminae V and VI); the highest number of labelled cells was detected in lamina VII. In adjuvant-injected cats, co-distribution of Fos-IR neurons and numerous Fos-IR glia-like cells in the dorsal and ventral horns was also found. Significant increases in the mean number of NADPH-d-reactive cells in lamina VII bilaterally and also in lamina I and in an area around the central canal (lamina X) contralaterally within the L6, L7, and S1 segments (P < 0.05) were also observed. In conclusion, activation of the nociceptive input during long-term inflammation of the GS muscles is associated with differential patterns of c-fos expression and NADPH-d reactivity and also with central neuronal hyperexcitability that contributes to bilateral facilitation of the PBSt MSRs.

Modulation of monosynaptic transmission by presynaptic inhibition during fictive locomotion in the cat

The effect of multisensory inputs onto the presynaptic inhibitory pathways affecting IA terminals was studied during fictive locomotion in decerebrated cats. The effect was evaluated from changes in amplitude of the monosynaptic excitatory postsynaptic potential (EPSP) measured in lumbosacral motoneurones. Responses were grouped and averaged according to their timing within the step cycle divided into five bins. Presynaptic inhibition was evoked by stimulating group I afferents from the posterior biceps-semitendinosus (PBSt) muscles and one of three cutaneous nerves: superficial peroneal (SP), sural and saphenous. Statistical analysis was applied to compare (1) EPSPs conditioned by PBSt input alone and those conditioned by the combined PBSt and cutaneous inputs, and (2) each bin dividing the step cycle to disclose phase-dependent changes. Results from 19 motoneurones showed that: (1) there was a significant phase-dependent modulation in EPSP amplitude (by 25%) with the maximum usually occurring during the depolarized phase; (2) PBSt alone reduced the EPSP amplitude (by 21%) in 3.2 bins on average; (3) combined PBSt and cutaneous stimuli further modified (up or down) the EPSP amplitude in half the trials but only in one to two bins; and (4) the most efficient cutaneous nerve (SP) usually decreased the PBSt-evoked reduction in EPSP size. Minimal changes in membrane input resistance suggest that the EPSP modifications were mostly due to presynaptic inhibition. Results indicate that muscle afferents can induce an important phase-dependent presynaptic inhibition of monosynaptic transmission and that concomitant activation of cutaneous afferents can alter this inhibition but only for a restricted part of the step cycle.

Only minor spinal motor reflex effects from feline group IV muscle nociceptors.

The contribution of group III and IV muscle nociceptors activated by injection of KCl or bradykinin into the muscle artery (i.a.) of the gastrocnemius-soleus muscle to spinal motor reflex pathways was investigated in high spinal cats. Group I-III fibres were completely blocked by TTX, leaving group IV-fibre conduction intact. Thus, effects from i.a. KCl or bradykinin injection persisting after TTX were attributed to TTX resistant group IV fibres while the contribution of group III fibres was approximately defined by the difference between those effects and the control effects before TTX. Confirming former findings the chemical activation of group III and IV muscle afferents induced distinct reflex facilitation of the flexor posterior biceps semitendinosus and inhibition of the extensor quadriceps. After the block of all myelinated fibres by TTX the same stimuli induced only minor reflex effects mediated by the persistently conducting TTX resistant group IV afferents. It is concluded that the main functional meaning of group IV muscle afferents, which respond preferentially with a higher threshold to mechanical stimuli, is probably less related to reflex motor control than that of group III afferents.

Ascending tract neurones processing information from group II muscle afferents in sacral segments of the feline spinal cord.

1. Ascending tract neurones located in the dorsal horn of sacral segments of the spinal cord have been investigated by extracellular and intracellular recording in the anaesthetized cat. The aim was to determine whether information from group II afferents that terminate within the sacral segments is conveyed to supraspinal structures and which types of neurones are involved. 2. A considerable proportion of ascending tract neurones found in the dorsal horn in the same segments as the pudendal (Onuf's) motor nucleus were excited by group II muscle afferents. The great majority (93%) of these neurones had axons ascending in ipsilateral funiculi. Spinocervical tract neurones constituted the largest proportion (82%) of such neurones, while very few spinocerebellar tract and propriospinal neurones and no postsynaptic dorsal column neurones were found among them. 3. In addition to activation by group II muscle afferents all of the neurones were strongly excited by cutaneous afferents. The most potent excitation was evoked by afferents of the posterior biceps-semitendinosus and gastrocnemius muscle nerves and by afferents of the cutaneous femoris, sural and pudendal nerves. The latencies of intracellularly recorded excitatory potentials were indicative of a high incidence of monosynaptic coupling between the afferents and ascending tract neurones. 4. The highly effective monosynaptic excitation of spinocervical tract neurones in the sacral segments by group II afferents is in contrast to the weak disynaptically mediated actions of group II afferents on such neurones in the L6-L7 segments but comparable to the actions of group II afferents on ascending tract neurones in the midlumbar segments. 5. Both the patterns of peripheral input and the latencies of synaptic actions in ascending tract neurones were similar to those in interneurones at the same locations (accompanying report). Similar information is therefore likely to be processed by both categories of neurones. 6. The role of sacral spinocervical tract neurones as a system for transmitting information from group II muscle afferents to supraspinal centres and the potential contribution of this system to the perception of limb position are discussed.

Declining inhibition elicited in cat lumbar motoneurons by repetitive stimulation of group II muscle afferents.

1. The aim of the present experiments was to verify whether group II inputs from gastrocnemius medialis (GM) muscle could elicit declining inhibitions similar to those observed during GM contractions in a variety of lumbar motoneurons of the cat spinal cord. Motoneurons were recorded intracellularly in chloralose- or pentobarbitone-anesthetized preparations during electrical stimulation of GM nerve with repetitive trains. 2. With strengths in the group I range, repetitive stimulation evoked the usual Ia excitation in homonymous motoneurons and excitatory postsynaptic potential (EPSP) amplitudes remained constant throughout the stimulation sequence. In synergic plantaris motoneurons lacking an excitatory connection with Ia afferents from GM, the same stimulation, kept at a constant strength throughout the stimulation sequence, elicited rapidly decreasing inhibitory potentials reminiscent of those evoked by GM contractions. 3. In motoneurons of pretibial flexors, quadriceps, and posterior biceps-semitendinosus, the stimulation strength required to observe declining inhibitions resembling those produced by GM contractions was 4-8 times group I threshold, engaging group II in addition to group I fibers. 4. These results show that input from GM group II plus group I afferents can elicit inhibitory effects in a variety of motoneurons. Such observations support the hypothesis that messages from spindle secondary endings and/or nonspecific muscle receptors activated during contraction might contribute to the widespread inhibition caused by GM contractions. 5. Inasmuch as constant input in group II and group I afferents evoked declining inhibitory potentials, the origin of the decline must be central, which suggests that the rapid reduction of contraction-induced inhibitions also depended on a central mechanism.

A relay for input from group II muscle afferents in sacral segments of the cat spinal cord.

1. A neuronal relay for input from group II afferents of hindlimb muscle nerves has been found in the previously little explored sacral segments of the cat spinal cord. 2. Electrical stimulation of group II muscle afferents of a number of nerves evoked negative potentials on the surface (cord dorsum potentials) and population postsynaptic potentials (field potentials) within the sacral segments. The largest potentials were evoked by stimulation of the posterior biceps-semitendinosus and triceps surae nerves which evoke much smaller potentials in other segments. Group II afferents of other nerves, notably those which have their main relay within the middle lumbar segments, were much less effective. 3. The sites at which cord dorsum and field potentials evoked by group II muscle afferents were recorded varied in relation to the external topography of the L7-S2 spinal segments but were consistent in their location relative to the pudendal motor nucleus (Onuf's nucleus). Potentials evoked by group II afferents of the posterior biceps and semitendinosus nerves peaked at a level corresponding to the rostral half of Onuf's nucleus and potentials evoked by afferents of the gastrocnemius nerves peaked just rostral to this nucleus. The largest field potentials (of 0.5-1.0 mV) were recorded within the dorsal horn. Field potentials in the intermediate zone were much smaller (< 0.3 mV) and were seen less frequently. 4. Evidence was obtained that the dorsal horn field potentials are to a great extent evoked monosynaptically by the fast conducting fraction of group II muscle afferents: (i) they were evoked at short latencies (2.4-2.7 ms from the stimulus; 1.3-1.7 ms from group I components of afferent volleys and 0.5-0.7 ms from group II components of these volleys), (ii) the conduction times of impulses in the fastest conducting fraction of group II afferents, between the sacral segments (where these impulses were induced by intraspinal stimuli) and the peripheral nerves, were only about 0.5 ms shorter than the latencies of field potentials recorded at the site of intraspinal stimulation and evoked by stimulation of the same peripheral nerves and, (iii) the field potentials followed repetitive stimuli without temporal facilitation. 5. Negative cord dorsum and field potentials were also evoked by small stretches of the semitendinosus and triceps surae muscles. Although they were smaller than potentials evoked by electrical stimulation of sensory fibres and appeared at longer latencies, their presence is consistent with a contribution of muscle spindle afferents to the actions of group II muscle afferents within the sacral segments.(ABSTRACT TRUNCATED AT 400 WORDS)

Synaptic effects in lumbar α-motoneurones evoked from group II muscle afferents via two different interneuronal pathways in the cat

Conditioning of monosynaptic reflexes was used to investigate group II excitation from quadriceps (Q) and sartorius (Sart) in posterior biceps-semitendinosus (PBSt) motoneurones and different lesions were made to analyze the interneuronal pathways. The purpose of the investigation was to find if the excitation from group II Q and Sart afferents, which enter the spinal cord in L4–L6, is relayed to motoneurones by interneurones located in these segments and/or in the same segments (L7–S1) as the PBSt motoneurones. In some experiments a transection of the dorsal column in L6, which interrupts the group II input from Sart and Q to interneurones in the L7–S1 segments, resulted in a marked decrease (by about 2 3 ) of group II excitation from these nerves. In other experiments the same lesion did not reduce the group II effect. In the latter cases the effect could be abolished by a second lesion of the lateral funiculus (LF) in L5–L6. It is postulated that potent effects from Q and Sart group II afferents can be evoked by interneurones located in L7–S1, i.e. in the same segments as the PBSt motoneurones (L7–S1), and/or via interneurones in more rostral segments. The axons of the more rostrally located group II interneurones appear to descend mainly in the middle part of the LF.

An intracellular study of muscle primary afferents during fictive locomotion in the cat

1. Presynaptic activity of identified primary afferents from flexor, extensor, and bifunctional hindlimb muscles was studied with intra-axonal recordings during fictive locomotion. Fictive locomotion appeared spontaneously in decorticate cats (n = 9), with stimulation of the mesencephalic locomotor region (n = 4), and in spinal cats injected with clonidine or nialamide and L-DOPA (n = 4). Representative flexor and extensor muscle nerves, recorded to monitor the locomotor pattern and dorsal rootlets of the sixth and seventh lumbar segments, were recorded simultaneously to monitor dorsal root potentials (DRPs). 2. From responses to muscle stretches and, in some instances, twitch contractions of the parent muscle, 75% of the single units examined were putatively identified as spindle afferents (40/53). On the basis of conduction velocity and stimulation threshold, 73% of these were further classified as group I fibers (29/40), the rest as group II fibers. 3. All units (n = 53 with resting potential more negative than -45 mV) showed fluctuations of their membrane potential (up to 1.5 mV) at the rhythm of the fictive locomotion. Subsequent averaging of these fluctuations over several cycles revealed that 89% of all units displayed a predominant wave of depolarization during the flexor phase, followed by a trough of repolarization. In 79% of the units, there was also a second, usually smaller, depolarization during the extensor phase. The relative size of each wave of depolarization could vary with different episodes of fictive locomotion in the same unit and among various afferents from the same muscle in the same experiment. 4. The firing frequency of some afferents from the ankle flexor tibialis anterior (5/16) and the bifunctional muscle posterior biceps-semitendinosus (4/15) was phasically modulated along the fictive step cycle. The maximum frequency always occurred during the flexor phase, i.e., during the largest depolarization of the unit. Because of the absence of phasic sensory input in the curarized animal, we assume that the phasic discharges were generated within the spinal cord and antidromically propagated. Phasic firing was never encountered in afferents from extensor muscles such as triceps surae (0/15) and vastus lateralis (0/4). 5. The results demonstrate that the pattern of rhythmic depolarization accompanying fictive locomotion is similar for the majority of flexor, extensor, and bifunctional group I (and possibly group II) muscle spindle primary afferents. They further indicate that there is a specific phasic modulation of antidromic firing for some flexor and bifunctional muscle spindle afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Primary afferent depolarization of central terminals of group II muscle afferents in the cat spinal cord.

1. The origin of primary afferent depolarization (PAD) of the central terminals of group II afferent fibres of tibialis anterior and extensor digitorum longus muscles has been investigated in the cat. Changes in the excitability of the terminals to intraspinal stimuli, upon application of conditioning stimuli to muscle nerves (quadriceps, sartorius, gracilis, posterior biceps-semitendinosus, anterior biceps-semimembranosus, gastrocnemius-soleus, deep peroneal), cutaneous nerves (sural, superficial peroneal) and the posterior nerve to the knee joint, were used as a measure of PAD. 2. PAD was most readily evoked by conditioning stimuli which were maximal for group II muscle afferents. However, some PAD was also evoked from group I afferents and evidence is presented that group Ia afferents contributed. Afferents of posterior biceps-semitendinosus and sartorius muscles appeared to be most effective. PAD was also evoked by stimulation of cutaneous and joint nerves, often in the same fibres which were affected by group Ia afferents. 3. It is concluded that there are several common sources of PAD of group II and group Ia afferent terminals on the one hand, and group Ib afferent terminals on the other. 4. The properties of PAD of group II afferents are discussed in relation to the problem of how PAD affects transmission from fibres with long terminal branches of small diameter.

Evidence of rhythmic inhibitory synaptic influences in hindlimb motoneurons during fictive locomotion in the thalamic cat.

Intracellular recordings of various motoneurons of proximal hindlimb muscles were performed on thalamic paralyzed cats, during fictive locomotion that was either spontaneous or evoked by stimulation of the subthalamic region. In motoneurons innervating sartorius (medialis and lateralis), vasti (intermedius, medialis and lateralis) and anterior biceps-semimembranous, one depolarization occurred in each locomotor cycle, alternating with a phase of repolarization that was synchronous with the activation of the antagonistic muscle nerve. This latter phase could be decreased or reversed by intracellular injection of chloride ions or current, revealing the presence of inhibitory inputs onto motoneurons. The pattern of membrane potential variations was more complex in motoneurons of rectus femoris and posterior biceps-semitendinosus muscles, but phases of chloride dependent inhibition were nevertheless identified, mainly during the sartorius nerve activation in the case of rectus femoris, and during the vasti and anterior biceps-semimembranosus nerve activations in the case of posterior biceps-semitendinosus. These inhibitory influences were shown to be controlled by the level of activity in exteroceptive afferents. The characteristics of the excitatory and inhibitory inputs to the hindlimb motoneurons identified here are discussed in relation with the organization of the central pattern generator for locomotion.

Presynaptic inhibition, EPSP amplitude, and motor-unit type in triceps surae motoneurons in the cat.

1. Composite group Ia excitatory postsynaptic potentials (EPSPs) produced by heteronymous nerve stimulation were recorded from triceps surae motoneurons of barbiturate-anesthetized cats. Motoneuron rheobase, input resistance, and axonal conduction velocity were measured, and motor units were classified on the basis of the mechanical responses of their muscle units. 2. The amplitude of EPSPs recorded from 33 medial gastrocnemius (MG) motoneurons ranged from 0.6 to 4.3 mV. The mean EPSP amplitude differed among the major MG motor-unit types, increasing in the order fast twitch, fast fatiguing (FF); fast twitch, fatigue resistant (FR); slow twitch, fatigue resistant (S) (FF less than FR less than S). The amplitude of EPSPs recorded from 15 soleus motoneurons ranged from 0.3 to 3.4 mV, with a mean of 1.4 mV. 3. Presynaptic inhibition of EPSPs was produced by trains of conditioning volleys in the posterior biceps-semitendinosus (PBST) nerve. In 33 MG cells PBST conditioning stimulation reduced the amplitude of EPSPs by 11-50%, with a mean inhibition of 27%. The amplitude of EPSPs in 15 soleus motoneurons was decreased by 5-84%, with a mean inhibition of 37%. 4. When the magnitude of presynaptic inhibition was expressed as percent inhibition, there was no relation between presynaptic inhibition and either motor-unit type or the amplitude of the EPSP. However, when presynaptic inhibition was expressed as the absolute amount of inhibition in millivolts, the magnitude of inhibition was highly correlated with EPSP amplitude both across the entire triceps surae population (MG, lateral gastrocnemius, soleus) as well as within each muscle population. This correlation was also significant within the MG FF and FR motor-unit populations. 5. We conclude that EPSP amplitude and not motor-unit type is the major determinant of the magnitude of presynaptic inhibition. However, because of the effect of motor-unit type on EPSP amplitude, the net effect is that presynaptic inhibition increases in the order FF less than FR less than S.

Crossed flexor reflex responses and their reversal in freely walking cats

Chronic muscular limb pain requires the adoption of motor patterns distinct from the classic ipsilateral flexion, crossed extension and corresponding reciprocal inhibitions to acute exteroceptive stimulation. Using selective chemical activation of group III/IV afferents in gastrocnemius-soleus (GS) muscles we investigated bilaterally their reflex responses conditioned by (a) acute ‘myositis’ induced by intramuscular carrageenan; and (b) sub-acute ‘myositis’ induced by infusion of complete Freund's adjuvant (CFA). Reflex transmission was detected by monosynaptic testing and c-fos staining used to identify increased neuronal activity. In all control experiments with chemical stimulation of group III/IV afferents, ipsilateral responses conformed to the flexor reflex pattern. However, the expected contralateral facilitation of GS motoneurones occurred in fewer than 50% trials while only 9% of trials induced contralateral inhibition of flexor posterior-biceps-semitendinosus (PBSt) motoneurones. During carrageenan acute myositis contralateral PBSt was transiently facilitated by selective activation of group III/IV afferents. During CFA-induced myositis, contralateral only inhibition of GS motoneurones occurred instead of any facilitation, while bidirectionally a crossed facilitation of PBST dominated. These reflex changes were mirrored in an enhanced number of neurones with enhanced c-fos expression. Muscle pain, particularly if chronically persistent, requires another behavioural response pattern than acute exteroceptive pain.

Segmental reflexes mediated by joint afferent neurons in cat knee.

1. Reflex effects mediated by knee joint afferent neurons were tested using the electrically evoked monosynaptic reflex in motoneurons innervating muscles which act about the knee. 2. Joint afferents were excited using small extension movements of the knee, stimuli which have been shown to be effective in activating a large fraction of the myelinated fibers in joint nerves. Because of the variability of reflex responses observed by others under similar experimental conditions, experimental control and data collection were done automatically under computer control. Large numbers of trials were presented in random sequence, and the resulting data were sorted and averaged. 3. Positive feedback was observed in both knee extensor (vasti) and knee flexor (posterior biceps-semitendinosus (PB-ST)) motoneuron populations. Vasti motoneurons were excited, and PB-ST motoneurons were inhibited by knee extensions when the posterior articular nerve (PAN) was intact; these effects were lost or substantially reduced when the PAN was cut. 4. Using knee extension stimuli, no reliable reflex effects were observed which could be attributed to afferents in medial articular nerve.

Tonic inhibitory influence of a supraspinal monoaminergic system on presynaptic inhibition of an extensor monosynaptic reflex

Presynaptic inhibition of the extensor (quadriceps, QUAD) monosynaptic reflex (MSR) in unanaesthetized decerebrate cats was antagonized by imipramine hydrochloride (2–5 mg/kg), 5-hydroxytryptophan (75 mg/kg) and a specific 5-hydroxytryptamine (5-HT) neuronal uptake blocker, fluoxetine hydrochloride (Lilly 110140, 0.25–6 mg/kg). These effects of imipramine and fluoxetine were partially reversed by the 5-HT antagonist, cyproheptadine hydrochloride (5 mg/kg), and completely reversed by the application of a thoracic cold block which prevents supraspinal inputs to the caudal spinal cord. Imipramine, however, failed to antagonize this inhibition in animals pretreated with either dl- p-chlorophenylalanine ( p-CPA, 300 mg/kg i.p. for 2 consecutive days) or dl-α-methyl- p-tyrosine methyl ester hydrochloride (α-MPT, 125 mg/kg i.p. 16 and 4 h prior to the experiment). Cyproheptadine (2.5–5 mg/kg), phenoxybenzamine hydrochloride (2.5–5 mg/kg) and a cold block enhanced the inhibition of this extensor MSR but a cold block failed to alter the inhibition in animals pretreated with p-CPA or α-MPT. Presynaptic inhibition of the flexor (posterior biceps-semitendinosus, PBST) MSR was however not blocked by imipramine, fluoxetine or a cold block nor enhanced by cyproheptadine or phenoxybenzamine. The effects of the drugs tested and a cold block on the excitability of the QUAD group Ia afferents were reciprocal to those on the MSR during presynaptic inhibition. The results of this study indicate that descending tonically active systems (1) involving 5-HT and noradrenaline, antagonize presynaptic inhibition of the QUAD but not the PBST-MSR, (2) decrease the excitability of the QUAD Ia afferents and (3) increase the excitability of QUAD motoneurones.

Effects of bicuculline on central inhibition

The effects of the specific gamma aminobutyric acid (GABA) antagonist bicuculline were investigated on direct, presynaptic and reticular inhibition and cerebellar disfacilitation of the segmental monosynaptic action potentials of decerebrate cats. Bicuculline markedly suppressed presynaptic inhibition of the quadriceps, posterior bicepssemitendinosus and gastrocnemius-soleus monosynaptic action potentials but had no effect on direct inhibition of these same potentials. Reticular inhibition of the quadriceps potentials was unaltered with bicuculline, but reticular inhibition of the posterior biceps-semitendinosus potentials was significantly suppressed. Cerebellar disfacilitation of both the quadriceps and posterior biceps-semitendinosus potentials was also blocked with bicuculline. The present study supports earlier propositions that GABA may be involved in presynaptic inhibition and cerebellar disfacilitation of the segmental potentials and suggests that reticular inhibition of the posterior biceps-semitendinosus monosynaptic action potentials may also be mediated by GABA.