Showing papers on "Motor neuron published in 1987"

Voluntary control of motor units in human antagonist muscles: coactivation and reciprocal activation

Abstract: 1. Myoelectric (ME) activity of several motor units was detected simultaneously from the human flexor pollicis longus and extensor pollicis longus muscles, the only two muscles that control the interphalangeal joint of the thumb. The ME signals were detected while the subjects produced isometric force outputs to track three different paradigms: triangular trajectories, random-force trajectories requiring both flexion and extension contractions, and net zero force resulting from stiffening the joint by voluntarily coactivating both muscles. 2. The ME signals were decomposed into their constituent motor-unit action potential trains. The firing rate behavior of the concurrently active motor units was studied using cross-correlation techniques. 3. During isometric contractions, the firing rates of motor units within a muscle were greatly cross-correlated with essentially zero time shift with respect to each other. This observation confirms our previous report of this behavior, which has been called common drive. Common drive was also found among the motor units of the agonist and antagonist muscles during voluntary coactivation to stiffen the interphalangeal joint. This observation suggests two interesting points: 1) that the common drive mechanism has a component of central origin, and 2) that the central nervous system may control the motoneuron pools of an agonist-antagonist muscle pair as if they were one pool when both are performing the same task. 4. During force reversals, the firing rates of motor units reverse in an orderly manner: earlier recruited motor units decrease their firing rate before later recruited motor units. This orderly reversal of firing rates is consistent with the concept of orderly recruitment and derecruitment. 5. A control scheme is suggested to explain the behavior of the motor units in both muscles during force reversal. It consists of centrally mediated reciprocally organized flexion and extension commands along with a common coactivation command to both muscles. This control scheme allows for coactivation and reciprocal activation of an agonist-antagonist set. 6. The agonist-antagonist pair was observed to generate a net force in two control modalities: proportional activation and reciprocal activation. In proportional activation, the agonist-antagonist set is coactivated during either of two states: when uncertainty exists in the required task or when a compensatory force contraction is perceived to be required.(ABSTRACT TRUNCATED AT 400 WORDS)

Magnetic and electrical transcranial brain stimulation: physiological mechanisms and clinical applications.

Abstract: The human brain can be stimulated by electric shocks or by brief intense magnetic fields. The latter cause only a trivial scalp sensation. Stimuli exciting the motor cortex cause contralateral muscle responses, but the threshold for excitation is markedly reduced by slight voluntary contraction of the target muscle. For small hand muscles, the overall latency from scalp to muscle is shorter by 1.8 ms when electrical stimuli are used than when stimuli are magnetic. Central motor conduction time (CMCT) can be estimated by stimulating over the scalp and then over the cervical area. In healthy subjects, the CMCT is 6.1 +/- 0.8 (SD) (n = 29). Physiological studies have shown that the facilitation of responses in hand muscles produced by voluntary contraction is also present when contralateral muscles are used, but not when a leg muscle is contracted. The mechanism of facilitation may involve neural activity at both spinal and cortical levels. Single motor units can be caused to discharge by threshold brain stimuli. These motor units are the same ones activated first during weak voluntary contractions. Clinical studies have shown that the CMCT may be greatly prolonged in patients with multiple sclerosis and that subclinical motor pathway lesions can be detected. Central conduction may also be abnormal in patients with motor neuron disease and cervical myelopathy. Side effects have not been encountered with either type of stimulator.

Synaptic potentials of primary afferent fibers and motoneurons evoked by single intermediate nucleus interneurons in the cat spinal cord.

Abstract: Spike-triggered averaging of dorsal and ventral root potentials was used in anesthetized cats to disclose possible synaptic connections of spinal interneurons in the intermediate nucleus with afferent fibers and/or motoneurons. With this method we have been able to document the existence of a distinct group of interneurons whose activity was associated with the recording of inhibitory potentials in the ventral roots (iVRPs), but not with negative dorsal root potentials (nDRPs). The iVRPs had mean durations of 60.8 +/- 22.1 ms and latencies between 1.7 and 5.1 ms relative to the onset of the interneuronal spikes. Within this group of neurons it was possible to characterize two categories depending on their responses to segmental inputs. Most type A interneurons were mono- or disynaptically activated by group I muscle afferents and polysynaptically by low threshold (1.08-1.69 X T) cutaneous fibers. Type B interneurons were instead polysynaptically activated by group II muscle and by cutaneous fibers with thresholds ranging from 1.02 to 3.1 X T. Whenever tested, both type A and B interneurons could be antidromically activated from Clarke9s columns. There was a second group of interneurons whose activity was associated with the generation of both iVRPs and nDRPs. These potentials had mean durations of 107.5 +/- 35.6 and 131.5 +/- 32 ms, respectively, and onset latencies between 1.7 and 6.1 ms. The interneurons belonging to this group, which appear not to send axonal projections to Clarke9s column, could be classified in three categories depending on their responses to peripheral inputs. Type C interneurons responded mono- or disynaptically to group I muscle volleys and polysynaptically to intermediate threshold (1.22-2.7 X T) cutaneous afferents. Type D interneurons were polysynaptically activated by group II muscle afferents (2.3-8.5 X T) and by intermediate threshold (1.4-3 X T) cutaneous fibers and type E interneurons only by group I muscle afferents with mono- or disynaptic latencies. A third group of interneurons produced nDRPs without iVRPs. The nDRPs had onset latencies varying from 1.9 to 6.2 ms and mean durations of 130.0 +/- 34.6 ms. These neurons (type F) showed spontaneous and evoked bursts of activity and were not antidromically activated from Clarke9s column. They responded to stimulation of low- and intermediate-threshold cutaneous fibers (1.04-2.9 X T) with mono- and polysynaptic latencies, but not by group I muscle fibers. Type F interneurons appear to be located in more superficial layers than all the other interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Motoneuron properties during motor inhibition produced by microinjection of carbachol into the pontine reticular formation of the decerebrate cat

Abstract: It is well established that cholinergic agonists, when injected into the pontine reticular formation in cats, produce a generalized suppression of motor activity (1, 3, 6, 14, 18, 27, 33, 50). The responsible neuronal mechanisms were explored by measuring ventral root activity, the amplitude of the Ia-monosynaptic reflex, and the basic electrophysiological properties of hindlimb motoneurons before and after carbachol was microinjected into the pontine reticular formation of decerebrate cats. Intrapontine microinjections of carbachol (0.25-1.0 microliter, 16 mg/ml) resulted in the tonic suppression of ventral root activity and a decrease in the amplitude of the Ia-monosynaptic reflex. An analysis of intracellular records from lumbar motoneurons during the suppression of motor activity induced by carbachol revealed a considerable decrease in input resistance and membrane time constant as well as a reduction in motoneuron excitability, as evidenced by a nearly twofold increase in rheobase. Discrete inhibitory postsynaptic potentials were also observed following carbachol administration. The changes in motoneuron properties (rheobase, input resistance, and membrane time constant), as well as the development of discrete inhibitory postsynaptic potentials, indicate that spinal cord motoneurons were postsynaptically inhibited following the pontine administration of carbachol. In addition, the inhibitory processes that arose after carbachol administration in the decerebrate cat were remarkably similar to those that are present during active sleep in the chronic cat. These findings suggest that the microinjection of carbachol into the pontine reticular formation activates the same brain stem-spinal cord system that is responsible for the postsynaptic inhibition of alpha-motoneurons that occurs during active sleep.

Myomodulin: a bioactive neuropeptide present in an identified cholinergic buccal motor neuron of Aplysia.

Abstract: When Aplysia are initially exposed to food stimuli, their biting responses show progressive increases in speed and strength The accessory radula closer (ARC) buccal muscles have been used to study this phenomenon, and it has been shown that changes in ARC muscle contraction are partially due to activity of a serotonergic neuron that modulates this muscle, by both a direct action and an action on two ARC motor neurons (B15 and B16) The motor neurons use acetylcholine as their excitatory transmitter, but they also contain bioactive peptides that can potentiate muscle contractions when they are exogenously applied Motor neuron B15 contains the structurally related small cardioactive peptides A and B, whereas motor neuron B16 contains a different peptide--termed myomodulin In the present study we determined the full amino acid sequence of myomodulin Myomodulin is present in the ARC muscle, and exogenous application of the peptide potentiates ARC muscle contractions in a manner similar to the potentiation by small cardioactive peptides A and B The structure of myomodulin, however, bears little resemblance to the small cardioactive peptides Thus it appears that ARC muscle contractions may be regulated by at least three distinct classes of neuromodulators: serotonin, the small cardioactive peptides, and myomodulin

Parallel processing of proprioceptive signals by spiking local interneurons and motor neurons in the locust.

Abstract: The connections made by afferents from a proprioceptor at the femorotibial joint in a hind leg of a locust, the femoral chordotonal organ (FCO), were determined by making intracellular recordings from motor neurons and spiking local interneurons in the central nervous system and from afferent cell bodies in the periphery. Staining the central projections of the afferent neurons with dye introduced into their axons at the receptor, and the intracellular injection of dye into motor neurons and interneurons, shows that the branches of all 3 types of neuron overlap in specific regions of neuropile. Afferents excited by a movement of the receptor apodeme that is equivalent to an imposed extension of the femorotibial joint excite flexor tibiae motor neurons and some spiking local interneurons with cell bodies at the ventral midline of the metathoracic ganglion. The opposite movement excites extensor tibiae motor neurons and a different set of spiking local interneurons. Spikes in afferents that excite flexor motor neurons evoke depolarizing potentials that follow each spike with a consistent central latency of approximately 1.5 msec. The amplitude of the depolarizing potentials is dependent upon the membrane potential of the motor neuron. This evidence points to the connection being direct and to the potentials' being EPSPs. Simultaneous recordings from certain spiking local interneurons and certain flexor motor neurons show that they receive many synaptic potentials in common and are driven in a parallel fashion by movements of the receptor apodeme. Spikes of some afferents evoke EPSPs in both neurons with the same consistency and latency. An afferent can therefore synapse directly upon a motor neuron and a spiking local interneuron. Each afferent synapses on several motor neurons and possibly upon several interneurons. In turn, each motor neuron and each interneuron receives inputs from several afferents.

Multiple neuropeptides in cholinergic motor neurons of Aplysia: evidence for modulation intrinsic to the motor circuit.

Abstract: Changes in Aplysia biting responses during food arousal are partially mediated by the serotonergic metacerebral cells (MCCs). The MCCs potentiate contractions of a muscle utilized in biting, the accessory radula closer (ARCM), when contractions are elicited by stimulation of either of the two cholinergic motor neurons B15 or B16 that innervate the muscle. We have now shown that ARCM contractions may also be potentiated by peptide cotransmitters in the ARCM motor neurons. We found that motor neuron B15 contains small cardioactive peptides A and B (SCPA and SCPB)--i.e., whole B15 neurons were bioactive on the SCP-sensitive Helix heart, as were reverse-phase HPLC fractions of B15 neurons that eluted like synthetic SCPA and SCPB. Furthermore, [35S]methionine-labeled B15 peptides precisely coeluted with synthetic SCPA and SCPB. SCPB-like immunoreactivity was associated with dense-core vesicles in the soma of B15 and in neuritic varicosities and terminals in the ARCM. B16 motor neurons did not contain SCPA or SCPB but contained an unidentified bioactive peptide. RP-HPLC of [35S]methionine-labeled B16s resulted in one major peak of radioactivity that did not coelute with either SCP and which, when subject to Edman degradation, yielded [35S]methionine in positions where there is no methionine in the SCPs. Exogenously applied B16 peptide potentiated ARCM contractions elicited by stimulation of B15 or B16 neurons. Thus, in this system there appear to be two types of modulation; one type arises from the MCCs and is extrinsic to the motor system, whereas the second type arises from the motor neurons themselves and hence is intrinsic.

Central motor conduction is abnormal in motor neuron disease.

Abstract: Conduction in the central motor pathways of the brain and spinal cord was studied in 12 patients with motor neuron disease. Six healthy volunteers served as controls. Transcutaneous electrical stimulation of the cortex, cervical cord, thoracic cord and conus medullaris was used to determine motor latencies to the biceps brachii, thenar eminence and tibialis anterior muscles. Prominent, and often asymmetrical, slowing of central motor conduction was demonstrated in seven of the 12 patients; these findings were most marked in the spinal cord and in most cases correlated with clinical features of corticospinal involvement. In general it was more difficult to excite motor pathways in the central nervous system in the patients with motor neuron disease than in control subjects. Evidence of subclinical involvement of central motor pathways was found in five patients. The central lesion in motor neuron disease may thus contribute more significantly to the clinical deficit than has been realised, since the clinical signs of the upper motor neuron lesion are often masked by the more obvious lower motor neuron features.

Central distribution of efferent and afferent components of the pudendal nerve in rat.

Abstract: Central distribution of efferent and afferent components of the pudendal nerve was examined in the rat by the horseradish peroxidase (HRP) method after HRP application to the central cut end of the pudendal nerve. The pudendal motoneurons were located in the dorsolateral, dorsomedial and lateral groups at L5 and L6. Each of the dorsolateral and dorsomedial groups constituted a slender longitudinal cell column. Pudendal motoneurons in the lateral group were scattered at L5, rostrodorsally to the dorsolateral group. The neurons in the dorsolateral and lateral groups were labelled with HRP applied to the nerve branch innervating the ischiocavernosus and sphincter urethrae muscles. The neurons in the dorsomedial group were labelled with HRP applied to the branch supplying the sphincter ani externus and bulbospongiosus muscles. Some dendrites of pudendal motoneurons in the dorsomedial group extended to the contralateral dorsomedial group. These crossing dendrites were observed not only in male rats but also in female. The average number of the pudendal motoneurons in the dorsolateral and dorsomedial groups were larger in male rats than in female. A few neurons of the intermediolateral nucleus at upper L6 were also labelled with HRP applied to the dorsalis penis (clitoridis) nerve. Axon terminals of the pudendal nerve were distributed, bilaterally with an ipsilateral predominance, to the gracile nucleus, as well as to the dorsal horn and dorsal commissural gray from L4 to S2. A few labelled axons were seen in the intermediolateral nucleus at L6 and S1. Axon terminals from the dorsalis penis nerve were distributed more medially in the dorsal horn than those from the perinealis nerve.

The development of hindlimb motor activity studied in the isolated spinal cord of the chick embryo

Abstract: The development of hindlimb motor activity was studied in an isolated preparation of the chick spinal cord. The motor output from lumbosacral segments was characterized by recording the pattern of ventral root and muscle nerve discharge in 6-14-d-old embryos. In addition, the synaptic drive underlying motoneuron activity was monitored electrotonically from the ventral roots. Spontaneous motor activity consisted of recurring episodes of cyclical motoneuron discharge. During development, both the number of cycles in each episode and the intensity of discharge in each cycle progressively increased. Monophasic, positive ventral root potentials accompanied each cycle of motoneuron discharge. Prior to the innervation of hindlimb muscles at stage 26, ventral root discharge was barely detectable despite the presence of large ventral root potentials. Following hindlimb muscle innervation, each cycle of activity was initiated by a brief, intense discharge that coincided with the rising phase of the ventral root potential. In embryos older than stage 30, the initial discharge was followed, after a delay, by a more prolonged discharge. The duration of ventral root potentials was shortest in the stage 26 embryos, but was similar in embryos at stage 29 and older. The developmental changes in the coordination of antagonist activity were documented by recording the pattern of discharge in sartorius (flexor) and caudilioflexorius (extensor) muscle nerves between stage 30 and stage 36. At stage 30 both sets of motoneurons were coactivated during the brief discharge that initiated each cycle. By stage 31 a second discharge occurred in each cycle. The second discharge was delayed in flexor, but not in extensor, motoneurons, which led to an alternating pattern of activity.(ABSTRACT TRUNCATED AT 250 WORDS)

The neck motor system of the fly Calliphora erythrocephala. I: Muscles and motor neurons

Abstract: 1. The electrophysiology of the four paired nerves innervating the fly's neck muscles were examined by extra- and intracellular recording and staining with Lucifer Yellow. 2. Units that responded to moving black and white gratings and that were, therefore, termed ‘visual’ were recorded in all four neck muscle nerves. These visual motor neurons were direction-selective responding most vigorously to a single direction by excitation. 3. The preferred direction and the field of view of visual motor neurons was specific for each of the four neck muscle nerves and generally reflected an organization into horizontal- and vertical-motion-sensitive units. 4. The response characteristics of visual motor neurons corresponded to the structural relationship between their dendrites and visual interneurons in the lobula plate or terminals of descending neurons that were themselves associated with specific lobula plate neurons. 5. Visual units were only a small fraction of all neck motor neurons. A non-visual motor neuron responding to mechanical stimulation of wing and antenna and four mechanosensory fibre tracts associated with the prothoracic neck motor neuropil are described in detail.

Spontaneous and evoked activity of fetal primary afferents in vivo.

Abstract: The first movements of the fetus are apparently random and spontaneous. Their onset coincides with the growth of dorsal root afferents into the spinal cord and it is possible that they are not simply a result of spontaneous motoneuron activity but are reflex responses to sensory stimulation. It is not clear what stimuli could normally evoke such reflexes because nothing is known of the properties of primary afferent neurons in the fetus. I have investigated this by making recordings from single dorsal root ganglion cells in fetal rats in vivo. The afferents have small, defined receptive fields and respond to mechanical stimulation of skin or muscle at intensities that might occur in utero. Many of them are also chemosensitive. Unlike postnatal afferents they display background activity which peaks at the same age as fetal movements. Repeated stimulation causes long-lasting increases of both background and evoked activity. Such sensory input is likely to have a considerable influence on fetal movements and on the development of spinal cord connections.

The neck motor system of the fly Calliphora erythrocephala. II: Sensory organization

Abstract: 1 The electrophysiology of the four paired nerves innervating the fly's neck muscles were examined by extra- and intracellular recording and staining with Lucifer Yellow 2 Units that responded to moving black and white gratings and that were, therefore, termed ‘visual’ were recorded in all four neck muscle nerves These visual motor neurons were direction-selective responding most vigorously to a single direction by excitation 3 The preferred direction and the field of view of visual motor neurons was specific for each of the four neck muscle nerves and generally reflected an organization into horizontal- and vertical-motion-sensitive units 4 The response characteristics of visual motor neurons corresponded to the structural relationship between their dendrites and visual interneurons in the lobula plate or terminals of descending neurons that were themselves associated with specific lobula plate neurons 5 Visual units were only a small fraction of all neck motor neurons A non-visual motor neuron responding to mechanical stimulation of wing and antenna and four mechanosensory fibre tracts associated with the prothoracic neck motor neuropil are described in detail

A reconsideration of the central pattern generator concept for locust flight

Abstract: Although it is generally agreed that locusts can generate flight similar rhythmic motor activity in the absence of sensory feedback from the wings, recent studies indicate that functional deafferentation produces significant changes in the flight motor pattern (Hedwig and Pearson 1984). These findings have raised doubts on the adequacy of the central pattern generator concept for the locust flight system (Pearson 1985). In this paper, we re-investigate the effects of deafferentation on the capacity of adult migratory locusts to generate the flight motor pattern. For this purpose, the experimental animals were dissected to various degrees, ranging from head-ventral nerve cord, to isolated pterothoracic nerve cord, and finally single isolated ganglion preparations. Flight motor activity was released by either wind stimulation, the more traditional method, or by applying octopamine (Sombati and Hoyle 1984; Stevenson and Kutsch 1986). In all cases the released motor activity was analysed, giving details of latency, and phase relationships between specific synergistic and antagonistic motor units, and then compared with the flight motor pattern generated by intact tethered locusts. This analysis shows that deafferentation, although reducing the frequency, does not necessarily disrupt the basic flight motor pattern. By using octopamine we could show that even isolated thoracic nerve cord preparations can generate activity, which in all major aspects corresponds to this motor program. This could also be shown for the fully isolated metathoracic ganglion and we provide some evidence that the mesothoracic ganglion may be capable of a similar performance. In addition to releasing flight activity, octopamine was also found to enhance the responsiveness of deafferentated locusts to wind stimulation. This resulted in a considerable elevation of the frequency and prolongation of the flight motor activity to values comparable to the performance of intact tethered locusts.

GABA-immunoreactivity in inhibitory motor neurons of the nematode Ascaris

Abstract: We have used GABA-specific antisera to detect GABA-immunoreactivity in the motor neurons of the ventral nerve cord of Ascaris. We find that a subset of the individually identifiable commissures of motor neurons is specifically stained. On the basis of the location and morphology of stained commissures and of the location of stained cell bodies in the ventral nerve cord, we conclude that the labeled neurons comprise all members of the VI (inhibiting ventral muscle; 13 cells) and DI (inhibiting dorsal muscle; 6 cells) classes of inhibitory motor neurons (Stretton et al., 1978; Walrond et al., 1985). This result supports previous suggestions (e.g., del Castillo et al., 1964b) that GABA is the neurotransmitter released by the inhibitory motor neurons of nematodes. In the anterior part of the animal, the inhibitory motor neuron commissures have small branches in the sublateral nerve cords that have not been previously described: VI commissures have dorsal sublateral branches, while DI cells have ventral branches. Posterior VI neurons have branches in the lateral nerve cords.

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

Abstract: 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.

Physiological consequences of a peptide cotransmitter in a crayfish nerve-muscle preparation

Abstract: The pentapeptide proctolin is colocalized with a conventional, conductance-increasing neurotransmitter in 3 of 5 excitatory motoneurons that innervate a posture-related tonic flexor muscle of the crayfish. It is released from these neurons in response to nerve impulses. Nanomolar concentrations of proctolin superfused on the tonic flexor muscle act postsynaptically to potentiate tension generated by a given level of depolarization. Proctolin alone has no detectable effect on muscle tension, nor does it alter the resting membrane potential of the muscle. Proctolin produces no detectable effect on the EPSPs of the 1 proctolinergic motoneuron that was examined. Neurally released proctolin can be selectively depleted from severed motor axons following prolonged, low-frequency stimulation; EPSPs reflecting conventional transmitter release are unaltered by this procedure. After proctolin depletion, tension generated by the motoneuron is greatly reduced. Taken together, these results indicate that the peptide secondary transmitter in this neuromuscular preparation is an important contributor to the magnitude of tension generated by the motoneuron, but since its effect is dependent on the depolarizing EPSPs of the conventional neurotransmitter, it does not contribute to the temporal aspects of tension generation. These aspects are controlled exclusively by the conventional neurotransmitter.

Inputs to intercostal motoneurons from ventrolateral medullary respiratory neurons in the cat.

Abstract: The investigation examined the synaptic input from medullary respiratory neurons in the nucleus retroambigualis (NRA) to external (EIM) and internal (IIM) intercostal motoneurons. Antidromic mapping revealed that 112/117 (96%) tested NRA units had axons descending into thoracic spinal cord with extensive arborizations at many thoracic segments, mainly contralaterally. The conduction velocities ranged from 10 to 105 m X s-1. The descending projections did not appear to be somatotopically arranged. Cross-correlation of the spike trains of NRA inspiratory units with the discharge of external intercostal nerves (performed usually with 4 contralateral nerves) showed significant narrow peaks only in 5 out of 40 averages. Of the 25 trigger units tested for the thoracic projection in this series of experiments, 24 were antidromically activated. Intracellular recordings were made from 52 IIMs [mean membrane potential 65.3 mV, central respiratory drive potentials (CRDPs) greater than 1 mV present in 23/52] and 53 EIM (mean membrane potential 54.3 mV, CRDPs in 31/53). During the depolarizing phase of the CRDPs, synaptic noise with frequent and apparently unitary EPSPs with amplitudes in excess of 1 mV was observed. Spike-triggered averages of synaptic noise were computed for 153 pairings between 137 NRA neurons and 105 contralateral intercostal motoneurons. Only four PSPs were revealed: two monosynaptic EPSPs between expiratory NRA units and IIMs and two probably disynaptic EPSPs between inspiratory NRA units and EIMs. When advancing the microelectrode down to the motoneuron pools, frequent recordings were made from interneurons with spontaneous respiratory discharge (inspiratory or expiratory) located dorsal and medial to the motor nuclei. The interneurons could be excited following stimulation of segmental afferents. It is concluded that monosynaptic connections between respiratory NRA neurons and intercostal motoneurons are rare (connectivity no more than approximately 4%). Segmental interneurons, interposed between the majority of descending respiratory axons and intercostal motoneurons, are likely to produce large unitary EPSPs and, thus, short-term synchronization in the discharge of intercostal motoneurons as observed by others.

Competition favouring inactive over active motor neurons during synapse elimination.

Abstract: During normal postnatal maturation, mammalian muscles undergo an orderly process of synapse elimination, whereby each muscle fibre loses all but one of the multiple inputs with which it is endowed at birth1. Experimental perturbations that increase or decrease the overall activity of nerve and/or muscle cause a corresponding increase or decrease in the overall rate of neuromuscular synapse elimination2–7. On other grounds it has been suggested that competition among motor neurons is important in determining which synapses survive and which are eliminated1,8–10. Would a difference in activity among the terminals at the same endplate affect the outcome of the competition and not just its rate? We investigated this issue by blocking activity for four days in a small fraction of the motor neurons innervating the neonatal rabbit soleus muscle. Twitch tensions of motor units were subsequently measured for both the active and inactive populations of neurons to assess whether the inactive neurons had lost fewer or more synapses than is normal. We found that inactive motor neurons have a significant advantage compared to active counterparts in control experiments, a finding opposite to that expected if the neuromuscular junction operated by classical 'Hebbian' rules of competition11.

Regeneration by supernumerary axons with synaptic terminals in spinal motoneurons of cats.

Abstract: Axons in the central nervous system (CNS) of mammals do not normally regrow if they are cut, which severely limits restoration of function after injury. We have studied the reactions of adult cat spinal α-motoneurons after chronic transection of their axons in the periphery by labelling single cells with horseradish peroxidase. Twelve weeks after the operation, about a third of the axotomized cells had developed a 'supernumerary' axon originating from the cell-body region. These supernumerary axons had variable trajectories and termination fields in the ipsilateral spinal cord but generally anomalous projections. Ultrastructural examination shows that they give rise to boutons that form morphologically normal synaptic contacts with neuronal profiles, although they contain dense-cored vesicles not normally seen1,2 in central terminals of α-motor axons. We conclude that axotomized neurons in the mammalian CNS may be able to form new synaptic contacts by means of supernumerary axons in the absence of local damage.

Stimulation of motor tracts in motor neuron disease.

Abstract: The muscle responses evoked by cortical and cervical stimulation in 11 patients with motor neuron disease were studied. The muscle potential in the abductor pollicis brevis, evoked by median nerve stimulation and the somatosensory potential evoked by wrist stimulation were also studied. In eight of 11 patients there was absence or increased central delay of the responses evoked by cortical stimulation. In four patients muscle responses on cervical stimulation and muscle action potentials on median nerve stimulation were also altered, indicating peripheral abnormalities. Somatosensory responses evoked by wrist stimulation were normal. Electrophysiological techniques are helpful in estimating the site of motor involvement in motor neuron disease.

Neurosecretory neurons and their projections to the serotonin neurohemal system of the cockroach Periplaneta americana (L.), and identification of mandibular and maxillary motor neurons associated with this system

Abstract: The neuroanatomy of a serotonin neurohemal system in the head of Periplaneta americana was studied by means of immunohistochemistry, cobalt backfilling, transmission electron microscopy, and nerve transection. This neurohemal system is supplied by bilateral groups of two or three neurons whose somata are located ventrally in the subesophageal ganglion, near the root of each mandibular nerve. Axons of these serotoninergic neurons extend into all of the nerves of the mouth parts but reach most of these nerves by a very circuitous route. Initially the axons extend from the subesophageal ganglion, through the ipsilateral mandibular nerve trunk, and into the third branch of the mandibular nerve. From here the axons extend into the second branch of the maxillary nerve by way of a link nerve, and then they project retrogradely to reenter the subesophageal ganglion. In the ganglion, branches of these axons extend into the labial nerves, and the axons run dorsally through the subesophageal ganglion, circumesophageal connectives, and tritocerebrum to reach the labral nerves. In the nerves of the mouth parts the serotoninergic axons give rise to numerous secondary branches that form an extensive neurohemal system at the surface of these nerves. The relatively large surface and cephalic location of this system probably indicate that the timely release of relatively large amounts of serotonin plays an important role in the physiology of feeding in this insect. The somata, neurites, and dendritic fields of the serotonin neurohemal neurons and those of the motor neurons of the mandibular abductor muscle occur together, and some of the mandibular abductor motor neurons also stain for serotonin. In order to distinguish clearly between these neurohemal and motor neurons, the anatomy of the mandibular abductor motor neurons has also been determined. Similarly, in the course of this study it has been necessary to work out the anatomy of the motor neurons of the maxillary retractor and cardo rotator muscles in order to distinguish them from the serotoninergic neurons. A nonserotoninergic peripheral neuron is associated with the serotonin neurohemal system, and its soma is located on the mandibular-maxillary link nerve. This link nerve neuron appears to be neurosecretory.

Discovery and partial characterization of primate motor-system toxins.

Abstract: beta-N-Oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) are chemically related excitant amino acids isolated from the seed of Lathyrus sativus (BOAA) and Cycas circinalis (BMAA), consumption of which has been linked to lathyrism (an upper motor neuron disorder) and Guam amyotrophic lateral sclerosis (ALS), respectively. Both diseases are associated with degeneration of motor neurons. Experimentally, single doses of BOAA or BMAA induce seizures in neonatal mice and postsynaptic neuronal oedema and degeneration in explants of mouse spinal cord and frontal cortex. Preliminary studies show that these behavioural and pathological effects are differentially blocked by glutamate-receptor antagonists. In macaques, several weeks of daily oral doses of BOAA produce clinical and electrophysiological signs of corticospinal dysfunction identical to those seen in comparably well-nourished animals receiving a fortified diet based on seed of Lathyrus sativus. By contrast, comparable oral dosing with BMAA precipitates tremor and weakness, bradykinesia and behavioural changes, with conduction deficits in the principal motor pathway. BOAA and BMAA (or a metabolite thereof) are the first members of the excitotoxin family to have been shown to possess chronic motor-system toxic potential. These observations provide a rational basis for searching for comparable endogenous neurotoxins in sporadic and inherited forms of human motor neuron disease.

Neurochemical and immunocytochemical studies on the distribution of N-acetyl-aspartylglutamate and N-acetyl-aspartate in rat spinal cord and some peripheral nervous tissues.

Abstract: HPLC analysis of rat spinal cord revealed a uniform distribution of N-acetyl-aspartate (NAA) across both longitudinal and dorsoventral axes. In contrast, ventral cord N-acetyl-aspartylglutamate (NAAG) levels were significantly higher than those measured in dorsal halves of cervical, thoracic, and lumbar segments. Immunocytochemical studies using an affinity-purified antiserum raised against NAAG-bovine serum albumin revealed an intense staining of motoneurons within rat spinal cord. Along with the considerable NAAG content in ventral roots, these results suggest that NAAG may be concentrated in motoneurons and play a role in motor pathways. NAAG was also present in other peripheral neural tissues, including dorsal roots, dorsal root ganglia, superior cervical ganglia, and sciatic nerve. It is interesting that NAA levels in peripheral nervous tissues were lower than those in CNS structures and that NAA levels in ventral roots and sciatic nerve were lower than NAAG levels. These findings further document a lack of correlation between NAAG and NAA levels in both central and peripheral nervous tissues. Taken together, these data demonstrate the presence of NAAG in nonglutamatergic neuronal systems and suggest a more complex role of NAAG in neuronal physiology than previously postulated.

Neurons in the dorsal motor nucleus of the vagus nerve are excited by oxytocin in the rat but not in the guinea pig.

Abstract: Intracellular recordings were obtained from vagal neurons and their response to oxytocin was investigated in slices from the rat and the guinea pig brainstem. After recording, Lucifer yellow was injected into the cells to verify their localization within the dorsal motor nucleus of the vagus nerve (dmnX). In the rat, virtually all neurons throughout the rostrocaudal extent of the dmnX increased their rate of firing in the presence of 10-1000 nM oxytocin and their membrane depolarized in a reversible concentration-dependent manner. This excitation was probably exerted directly on the impaled cells rather than being synaptically mediated, since it persisted in a low calcium/high magnesium medium or in the presence of tetrodotoxin. These data provide evidence for a direct membrane effect of oxytocin on a defined population of neurons in the rat brain. In the guinea pig, vagal neurons were fired by glutamate but were not excited by oxytocin, even though we detected many more oxytocin-immunoreactive structures in the guinea pig dmnX than in the rat dmnX. Therefore, homologous nuclei in the brains of two closely related mammals differ markedly in the density of oxytocinergic axons they contain. Unexpectedly, the magnitude of the electrophysiological effects of oxytocin on vagal neurons appeared inversely related to the amount of oxytocin-like immunoreactivity present in dmnX.