The role of capsaicin-sensitive muscle afferents in fatigue-induced modulation of the monosynaptic reflex in the rat.
(1/183)
1. The role of group III and IV afferent fibres of the lateral gastrocnemious muscle (LG) in modulating the homonymous monosynaptic reflex was investigated during muscle fatigue in spinalized rats. 2. Muscle fatigue was induced by a series of increasing tetanic electrical stimuli (85 Hz, 600 ms) delivered to the LG muscle nerve. Series consisted of increasing train numbers from 1 to 60. 3. Potentials from the spinal cord LG motor pool and from the ventral root were recorded in response to proprioceptive afferent stimulation and analysed before and during tetanic muscle activations. Both the pre- and postsynaptic waves showed an initial enhancement and, after a '12-train' series, an increasing inhibition. 4. The enhancement of the responses to muscle fatiguing stimulation disappeared after L3-L6 dorsal root section, while a partial reflex inhibition was still present. Conversely, after section of the corresponding ventral root, there was only a reduction in the inhibitory effect. 5. The monosynaptic reflex was also studied in animals in which a large number of group III and IV muscle afferents were eliminated by injecting capsaicin (10 mM) into the LG muscle. As a result of capsaicin treatment, the fatigue-induced inhibition of the pre- and postsynaptic waves disappeared, while the response enhancement remained. 6. We concluded that the monosynaptic reflex inhibition, but not the enhancement, was mediated by those group III and IV muscle afferents that are sensitive to the toxic action of capsaicin. The afferents that are responsible for the response enhancement enter the spinal cord through the dorsal root, while those responsible for the inhibition enter the spinal cord through both the ventral and dorsal roots. (+info)
Temporal overlap of excitatory and inhibitory afferent input in guinea-pig CA1 pyramidal cells.
(2/183)
1. The temporal interaction of evoked synaptic excitation and GABAA-mediated inhibition was examined in CA1 pyramidal cells. Single and paired intracellular recordings were carried out in pyramidal cell dendrites and somata, and interneurons of the guinea-pig hippocampal slice. Current-clamp, sharp electrode and whole-cell voltage-clamp recordings were made. 2. Kinetics of dendritic and somatic inhibitory responses were similar. Notably, kinetics of dendritic unitary IPSPs were as fast as kinetics of somatic unitary IPSPs. 3. GABAA-mediated influences were present throughout the orthodromic pyramidal cell EPSP/EPSC. Comparison of the kinetics of pharmacologically isolated monosynaptic IPSPs, IPSCs and inhibitory conductances (g GABAA), showed fastest kinetics for g GABAA. Close temporal overlap was observed between monosynaptic g GABAA and the rising phase of the evoked EPSP/EPSC. The onset of g GABAA coincided with or preceded onset of the EPSP/EPSC. 4. Onsets of feedforward IPSPs coincided with the rising phase of the pyramidal cell EPSP in > 80 % of paired recordings. Fastest feedforward inhibitory responses exerted near complete overlap with evoked excitation. 5. Onsets of recurrent IPSPs did not occur during the rising phase of the evoked EPSP, but > 3.0 ms after the peak of the pyramidal cell EPSP. 6. Orthodromically evoked interneuron spikes were observed at stimulation intensities that were below the threshold for eliciting EPSPs in concomitantly recorded pyramidal cells. The activation of feedforward inhibitory responses by weakest excitatory input, and the large temporal overlap between feedforward inhibition and evoked excitation, suggest that in situ any excitatory input in CA1 is effectively controlled by fast synaptic inhibition. (+info)
Neurotrophin modulation of the monosynaptic reflex after peripheral nerve transection.
(3/183)
The effects of neurotrophin-3 (NT-3) and NT-4/5 on the function of axotomized group Ia afferents and motoneurons comprising the monosynaptic reflex pathway were investigated. The axotomized medial gastrocnemius (MG) nerve was provided with NT-3 or NT-4/5 for 8-35 d via an osmotic minipump attached to its central end at the time of axotomy. After this treatment, monosynaptic EPSPs were recorded intracellularly from MG or lateral gastrocnemius soleus (LGS) motoneurons in response to stimulation of the heteronymous nerve under pentobarbital anesthesia. Controls were preparations with axotomized nerves treated directly with vehicle; other axotomized controls were administered subcutaneous NT-3. Direct NT-3 administration (60 microgram/d) not only prevented the decline in EPSP amplitude from axotomized afferents (stimulate MG, record LGS) observed in axotomy controls but, after 5 weeks, led to EPSPs larger than those from intact afferents. These central changes were paralleled by recovery of group I afferent conduction velocity. Removal of NT-3 4-5 weeks after beginning treatment resulted in a decline of conduction velocity and EPSP amplitude within 1 week to values characteristic of axotomy. The increased synaptic efficacy after NT-3 treatment was associated with enhanced connectivity of single afferents to motoneurons. NT-4/5 induced modest recovery in group I afferent conduction velocity but not of the EPSPs they elicited. NT-3 or NT-4/5 had no effect on the properties of treated motoneurons or their monosynaptic EPSPs. We conclude that NT-3, and to a limited extent NT-4/5, promotes recovery of axotomized group Ia afferents but not axotomized motoneurons or the synapses on them. (+info)
Peripheral mononeuropathy induced by loose ligation of the sciatic nerve in the rat: behavioral, electrophysiological and histopathologic studies.
(4/183)
The relationship between clinical parameters and pathological changes was investigated in an animal model of mononeuropathy, by behavioral, electrophysiological and histopathological methods. Mononeuropathy was induced in rats by loosely tying ligatures around the sciatic nerve. Eighty-four rats were used, and these were divided into fourteen groups to determine chronological changes in the withdrawal reflex latency, nerve conduction velocity and ultrastructure of the nerve from 1 to 84 days after nerve ligation surgery. Pathological changes around the ligated nerves were divisible in three phases: the first week was an inflammatory phase, when axonal degeneration, phagocyte infiltration and interstitial edematous changes were observed. The second and third weeks were a nerve-sprouting phase, when numerous axonal sprouts and remyelination were seen. The fourth to twelfth weeks were a recovery phase in which maturing myelination and interstitial fibrosis were characteristic. In the inflammatory phase, withdrawal reflex latencies were shortened, and sensory nerve conduction velocities (SCV) and motor nerve conduction velocities (MCV) gradually decreased. In the nerve-sprouting phase, the latency values remained low, and SCV and MCV were minimal. The parameters examined gradually returned to control levels during the recovery phase. In conclusion, these findings increase the knowledge of disease progression in mononeuropathy with hyperalgesia in human and animal models. (+info)
Monosynaptic Ia pathways at the cat shoulder.
(5/183)
1. The study aimed to describe in cat forelimb and shoulder motoneurones the convergence and projection patterns from large muscle spindle afferents (Ia). In 11 chloralose-anaesthetized cats maximum Ia EPSPs evoked by electrical stimulation of ipsilateral forelimb nerves were obtained in 309 intracellularly recorded alpha-motoneurones. 2. Groups of motor nuclei displayed similar Ia patterns. As in the distal forelimb they were often interconnected by bidirectional pathways, which were used to combine Ia synergistic groups. Three such groups are described at the shoulder. 3. The first group was composed of the main flexors of the scapulo-humeral joint. Regular disto-proximal Ia excitation from elbow extensors (and median afferents) indicates a coupling of flexion in the scapulo-humeral joint to the angular position of the elbow. 4. The second group comprised the outward rotators of the humerus with differentiated Ia convergence onto the different group members. The patterns of Ia excitation received and sent by the group members demonstrate that the outward rotators are incorporated in versatile synergisms and may occupy a central position in steering forelimb movements. 5. The third group was formed by the spinatus muscle and the subscapularis. This arrangement is suggested by the common convergence onto them from the elbow extensors and flexors. The pattern may serve to guide and keep the humeral head in the joint capsule. 6. The Ia synergistic groups receive Ia convergence from muscles acting at distant joints and also project to distant muscles. This is discussed as part of an extended pattern of Ia connections along the forelimb. In this way the shoulder muscles would be incorporated in flexor and extensor oriented synergisms which are needed to co-ordinate the muscular activation along the multijoint forelimb during locomotion. When the shoulder Ia pathways are compared with those in the distal forelimb, organization of the Ia system apparently follows a few basic principles which have adapted to the mechanical situation at the particular joints and their mechanical interaction. (+info)
The effect of firing on the excitability of a model motoneurone and its implications for cortical stimulation.
(6/183)
1. To help clarify the use of measurements of 'excitability', a simple model motoneurone receiving noisy tonic background excitation was tested with brief stimuli. Its response was determined from its PSTH (post-stimulus time histogram). The tonic background was varied from well below to well above the threshold for tonic firing. The conclusions should apply to many other neurones. 2. The response of the model to a stimulus depended upon a number of factors, including stimulus strength, synaptic membrane noise and especially whether or not the background drive elicited tonic firing. With the onset of firing, the shape of the stimulus-response curve changed drastically and the model then responded to the smallest stimulus without a threshold. When the drive was subthreshold, increasing the background excitation always increased the response to a given stimulus. However, what happened when the tonic drive exceeded the threshold for tonic firing depended upon the stimulus strength. With weak stimuli, the response increased with the drive to reach a plateau level where it was independent of the background firing rate; this occurred for stimuli comparable in size to the synaptic noise. With stronger stimuli, the response rose to a maximum for very low firing rates, but then decreased by up to 50 % to a plateau for high firing rates. Increasing the membrane noise reduced or abolished the maximum. 3. The model was also used to simulate a monosynaptic conditioning-testing paradigm. The effect of a given conditioning stimulus was then found to change with the onset of firing, including when the strength of the testing stimulus was adjusted to make the size of the test response the same in the presence and absence of firing. 4. The behaviour of real motoneurones can be expected to be at least as complex with the transition from silence to firing, so H reflex and other tests of 'excitability' must then be treated with caution. In particular, as has been observed experimentally, the response of a unit may decrease with increasing background excitation, as well as with inhibition. 5. Transferring the findings to corticospinal neurones makes it unlikely that the magnitude of the descending volley elicited by a given cortical stimulus ('excitability') will always increase with the initial level of cortical activity. In addition, the appreciable threshold for transcranial magnetic stimulation during voluntary contraction suggests that it first excites axons rather than the neural pacemakers. (+info)
Evidence for strong synaptic coupling between single tactile afferents and motoneurones supplying the human hand.
(7/183)
1. Electrical stimulation of digital nerves elicits short-latency excitatory and inhibitory spinal reflex responses in ongoing EMG in muscles acting on the fingers and thumb. Similar responses are elicited by stimulating a population of muscle spindles but not when a single muscle spindle is activated. The current study investigated whether short-latency EMG responses could be evoked from the discharge of a single cutaneous afferent. 2. Thirty-three tactile afferents were recorded via tungsten microelectrodes in the median nerve of awake humans. Spike-triggered averaging revealed EMG events time-locked to the afferent discharge. The afferents were activated by an external probe and the EMG was elicited by a weak voluntary contraction. 3. Eleven cutaneous afferents (33 %) showed a short-latency response in the ongoing EMG. Overt increases or decreases in EMG were observed for seven afferents (onset latency 20.0-41.1 ms). For four slowly adapting (SA) type II afferents, EMG showed a periodicity that was correlated to the afferent interspike interval (r = 0.99). 4. The EMG associated with two rapidly adapting (FA) type I afferents (29 %) showed a short-latency excitation while five showed neither excitation nor inhibition. Seven SA II afferents (39 %) showed excitation and 11 no response; and none of the six SA I afferents showed any response. 5. We conclude that, unlike muscle spindle afferents, the input from a single cutaneous afferent is strong enough to drive, via interneurones, motoneurones supplying muscles acting on the digits. The potent short-latency response we found supports the important role of cutaneous mechanoreceptors in fine motor control of the human hand. (+info)
Action potential reflection and failure at axon branch points cause stepwise changes in EPSPs in a neuron essential for learning.
(8/183)
In leech mechanosensory neurons, action potentials reverse direction, or reflect, at central branch points. This process enhances synaptic transmission from individual axon branches by rapidly activating synapses twice, thereby producing facilitation. At the same branch points action potentials may fail to propagate, which can reduce transmission. It is now shown that presynaptic action potential reflection and failure under physiological conditions influence transmission to the same postsynaptic neuron, the S cell. The S cell is an interneuron essential for a form of nonassociative learning, sensitization of the whole body shortening reflex. The P to S synapse has components that appear monosynaptic (termed "direct") and polysynaptic, both with glutamatergic pharmacology. Reflection at P cell branch points on average doubled transmission to the S cell, whereas action potential failure, or conduction block, at the same branch points decreased it by one-half. Each of two different branch points affected transmission, indicating that the P to S connection is spatially distributed around these branch points. This was confirmed by examining the locations of individual contacts made by the P cell with the S cell and its electrically coupled partner C cells. These results show that presynaptic neuronal morphology produces a range of transmission states at a set of synapses onto a neuron necessary for a form of learning. Reflection and conduction block are activity-dependent and are basic properties of action potential propagation that have been seen in other systems, including axons and dendrites in the mammalian brain. Individual branch points and the distribution of synapses around those branch points can substantially influence neuronal transmission and plasticity. (+info)