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Biomedical subjects

W D Snider

Publications and source records attributed to W D Snider.

79 records · Page 5Linked to original sources

Enhancement of synaptic function in cat motoneurones during peripheral sensory regeneration.

1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from medial (m.g.) and lateral gastrocnemius (l.g.) motoneurones in the cat 2-30 weeks after crushing the m.g. nerve.2. The mean amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were initially depressed (2-3 weeks after injury) and subsequently reached levels greater than normal for a period (8-12 weeks) before slowly declining to about 70% of the normal values (by week 30).3. Monosynaptic e.p.s.p.s evoked in m.g. motoneurones from the intact l.g. nerve showed neither initial depression nor subsequent alterations following crush of the m.g. nerve.4. By the eighth week after nerve crush, about 70% of Group I and Group II sensory fibres in the m.g. nerve responded to muscle stretch, about 15% had regenerated into the muscle but did not respond to muscle stretch, and the remainder failed to regenerate across the neuroma formed by the nerve crush.5. Homonymous, monosynaptic e.p.s.p.s produced by impulses in single sensory fibres responding to stretch of the m.g. muscle were recorded 8 weeks after crush of the m.g. nerve. Their amplitude distribution was indistinguishable from that obtained in normal, unoperated cats. Thus, there was no evidence that functionally reinnervated sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s observed during peripheral regeneration.6. When the m.g. nerve had been sectioned and prevented from regenerating into the muscle for 8 weeks, the amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were significantly smaller than those observed in control animals. Thus, there was no evidence that non-regenerating sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s after nerve crush.7. It is suggested that the sensory fibres responsible for abnormally large composite e.p.s.p.s following nerve crush are those that regenerate into the muscle but do not achieve functional reinnervation. This possibility is discussed in relation to the increase in central synaptic efficacy observed after prolonged disuse of the sensory pathway.

Animals↗

Reaction of synapses on motoneurones to section and restoration of peripheral sensory connexions in the cat.

1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s.) were recorded from triceps surae motoneurones of the cat 2-8 months after section of the medial gastrocnemius nerve whose regeneration into the muscle was prevented. In other animals, the cut nerve was reunited to the muscle with a post-denervation delay varying from 2 to 6 months, and the e.p.s.p.s were recorded 2 months later. The e.p.s.p.s were evoked by stimulation of the medial gastrocnemius nerve central to the site of the section or reunion. 2. The mean amplitudes of the e.p.s.p.s decreased with time after nerve section, virtually disappearing by the eighth post-operative month. The decrement of the e.p.s.p. amplitude occurred more quickly in soleus motoneurones than in medial or lateral gastrocnemius motoneurones. 3. The e.p.s.p.s evoked in medial or lateral gastrocnemius motoneurones from the cut medial gastrocnemius nerve returned to normal levels 2 months after reunion of the cut nerve even following a post-denervation delay of 6 months. However, in soleus motoneurones the e.p.s.p. recovery was incomplete. 4. The degree of functional motor reinnervation of the medial gastrocnemius muscle depended upon the post-denervation delay preceding the reunion operation. With a delay of 6 months before the reunion, the muscle showed no or only weak contractions in response to nerve stimulation. 5. Axotomized medial gastrocnemius motoneurones showed a significant decrease in conduction velocity and significant increase in the amplitude of overshoot of action potentials. The changes persisted even when the cut nerve was reunited to the muscle 2-6 months after denervation. 6. When the cut medial gastrocnemius nerve was reunited to the muscle 4 months after denervation, most of the sensory fibres, tested 2 months later, failed to respond to muscle stretch. 7. It is concluded that recovery of monosynaptic e.p.s.p.s following reconnexion of the cut nerve with its muscle does not require recovery of muscle activity, full restoration of sensory activity or the recovery of normal motoneurone properties. 8. It is also suggested that the degree to which central synaptic efficacy declines and recovers following section and regeneration of a peripheral nerve depends partly upon the type of motoneurone (fast phasic or slow tonic) with which the sensory fibres form synaptic connexions.

Animals↗

A physiological correlate of disuse-induced sprouting at the neuromuscular junction.

Recent investigations have established that many of the normal properties of muscle fibres are maintained, at least in part, by muscle activity. Thus, a fall in resting membrane potential, an increase in input resistance, and spread of acetylcholine receptors to extrajunctional sites can all be induced by abolishing muscle activity and prevented by direct stimulation of denervated muscle fibres. Muscle activity also exerts a trophic influence on the innervating motoneurones; furthermore it may be a factor in the regulation of sprouting. Brown and Ironton found fine, "ultra-terminal sprouts" emanating from the endplates of muscles rendered inactive by chronic conduction block of the muscle nerve. Pestronk and Drachman saw increased branching of the motor nerve terminal and a consequent increase in endplate size in similar conditions. If these sprouts at the endplates of inactive muscles were functional, one might expect more transmitter to be released in response to nerve stimulation. We report here that both quantum content and spontaneous miniature endplate potential (m.e.p.p) frequency are increased at the terminals of inactive (disused) muscles.

Acetylcholine↗

Dependence of motoneurone properties on the length of immobilized muscle.

1. The soleus muscle of adult cats was fixed in a shortened or lengthened position for 2 weeks by immobilizing the leg with a plaster cast. To eliminate the effects of reflex activity arising from the muscle, the lumbosacral dorsal roots were sectioned on the side of leg immobilization.2. The soleus muscle showed a significant decrease in weight after immobilization in a shortened position. Immobilization of the muscle in a lengthened position produced no significant changes in its weight.3. Two weeks after transection of the throacic spinal cord, the soleus muscle showed a significant decrease in weight. This decrease was prevented by immobilization of the muscle in a lengthened position. Immobilization in a shortened position caused no further muscle atrophy in cord-transected animals.4. Soleus motoneurones showed a significant decrease in the duration of after-hyperpolarization (a.h.p.) 2 weeks after immobilization of the muscle in a shortened position, whereas immobilization of the muscle in a lengthened position caused no significant changes in the duration of a.h.p.5. A decrease in the duration of a.h.p. of soleus motoneurones induced by cord transection was significantly prevented by immobilization of the muscle in a lengthened position but not by immobilization in a shortened position.6. In a variety of experimental conditions, the mean duration of a.h.p. of soleus motoneurones was significantly correlated with the soleus muscle: body wt. ratio.7. It is concluded that certain motoneurone properties depend upon the condition of the innervated muscle and that the primary factor responsible for the trophic influence is metabolic change in the muscle rather than contractile activity itself.

Animals↗

Disuse enhances synaptic efficacy in spinal mononeurones.

1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from triceps surae motoneurones in the cat following section or chronic conduction block of the medial gastrocnemius (m.g.) nerve with tetrodotoxin (TTX) or after daily stimulation of the sciatic nerve. 2. The mean maximum amplitudes of homonymous and heteronymous monosynaptic e.p.s.p.s evoked by stimulation of the mg. nerve were reduced significantly between 1 and 2 weeks after section of the muscle nerve. The mean amplitudes of monosynaptic e.p.s.p.s produced in the same motoneurones by afferent volleys from the intact synergists showed no significant alterations. 3. Reduction of the amplitude of monosynaptic e.p.s.p.s. evoked by the sectioned m.g. afferent volleys was not prevented by daily stimulation of the sciatic nerve. The chronic stimulation of the sciatic nerve did not increase the amplitude of monosynaptic e.p.s.p.s evoked by stimulation of the intact, lateral gastrocnemius (l.g.) or soleus nerve. 4. Chronic conduction block of the intact m.g. nerve with TTX cuffs for 2 weeks resulted in a significant increase in the homonymous e.p.s.p. amplitude. The amplitude of the heteronymous e.p.s.p.s evoked in the same m.g. motoneurones by stimulation of the intact l.g. or soleus nerve showed no significant changes. 5. It is concluded that decreased central synaptic transmission following section of the peripheral nerve is not due to elimination of impulse activity (disuse) of the sensory input and that prolonged disuse of the sensory fibres causes an increase, rather than a decrease, in central synaptic efficacy.

Animals↗

Diazepam and dialysis encephalopathy.

A patient with the clinical and electroencephalographic features of dialysis encephalopathy exhibited dramatic improvement with the initiation of diazepam therapy. Although improvement was sustained for a period of several weeks, her clinical condition eventually deteriorated despite continued treatment with diazepam and dialysis. Dialysis encephalopathy in this patient is compared with other cases recently reported in the medical literature as having a similar dramatic response to diazepam. It is concluded that diazepam transiently reverses a component of the dialysis encephalopathy syndrome, but it does not appear to change the ultimate prognosis for patients with this condition.

Brain Diseases↗

Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death.

Current ideas about the dependence of neurons on target-derived growth factors were formulated on the basis of experiments involving neurons with projections to the periphery. Nerve growth factor (NGF) and recently identified members of the NGF family of neuronal growth factors, known as neurotrophins, are thought to regulate survival of sympathetic and certain populations of sensory ganglion cells during development. Far less is known about factors that regulate the survival of spinal and cranial motor neurons, which also project to peripheral targets. NGF has not been shown to influence motor neuron survival, and whether the newly identified neurotrophins promote motor neuron survival is unknown. We show here that brain-derived neurotrophic factor (BDNF) is retrogradely transported by motor neurons in neonatal rats and that local application of BDNF to transected sciatic nerve prevents the massive death of motor neurons that normally follows axotomy in the neonatal period. These results show that BDNF has survival-promoting effects on motor neurons in vivo and suggest that BDNF may influence motor neuron survival during development.

Animals↗