637 research outputs found
Pre- and post-synaptic roles of action potential activity in synapse elimination revealed by using ectopic neuromuscular junction formation by a foreign nerve
No full textThe formation of the neuromuscular junction (nmj) is based on molecular cascades initiated by neural agrin as well as electrical activity in the neuromuscular structures. This review focuses on the latter factor, emphasizing the multiplicity of its mechanisms in the process of synapse elimination following initial polyneuronal innervation. Pre- and post-synaptic components of activity have in fact been identified through experiments on an adult model of nmj formation: ectopic reinnervation of the rat soleus muscle by the fibular nerve. Two activity-dependent elimination processes are thus compared: competition between distributed nmjs, which depends on evoked muscle impulse activity, and competition between axons converging on single nmjs, which instead depends on differences in the timing of impulses in the converging axons
Adult rat motor neurons do not re-establish electrical coupling during axonal regeneration and muscle reinnervation.
No full textGap junctions (GJs) between neurons are present in both the newborn and the adult nervous system, and although important roles have been suggested or demonstrated in a number of instances, in many other cases a full understanding of their physiological role is still missing. GJs are expressed in the rodent lumbar cord at birth and mediate both dye and electrical coupling between motor neurons. This expression has been proposed to mediate: (i) fast synchronization of motoneuronal spike activity, in turn linked to the process of refinement of neuromuscular connections, and (ii) slow synchronization of locomotor-like oscillatory activity. Soon after birth this coupling disappears. Since in the adult rat regeneration of motor fibers after peripheral nerve injury leads to a recapitulation of synaptic refinement at the target muscles, we tested whether GJs between motor neurons are transiently re-expressed. We found that in conditions of maximal responsiveness of lumbar motor neurons (such as no depression by anesthetics, decerebrate release of activity of subsets of motor neurons, use of temporal and spatial summation by antidromic and orthodromic stimulations, testing of large ensembles of motor neurons) no firing is observed in ventral root axons in response to antidromic spike invasion of nearby counterparts. We conclude that junctional coupling between motor neurons is not required for the refinement of neuromuscular innervation in the adult
Lesson from the neuromuscular junction: role of pattern and timing of nerve activity in synaptic development
No full text[No abstract available
The use of in vivo direct drug application to assess neural regulation of muscle properties.
No full textSkeletal muscle is a convenient model system for studying basic questions on the neural regulation of synaptogenesis and of many properties of sarcolemma and contractile apparatus. The study of the neural signals involved in a particular regulation and of the mediating intracellular pathways, requires the chronic application of drugs, second messengers, antibodies, trophic factors and the like. The most common way of application is in vitro treatment of muscle cell lines or primary myotube cultures. As an alternative to tissue culture, we developed a technique for in vivo application of the agents under study directly on skeletal muscle. An initial surgical step secures the tip of a fine polyethylene catheter (≤250 μm) onto the proximal surface of the adult rat soleus muscle. The onset of perfusion of the solution containing the agent, however, starts only 10–15 days later, pushed by an implanted Alzet pump connected to the catheter. After chronic in vivo treatment for the appropriate number of days, the muscle is processed as needed. We used various agents which are known to affect muscle fibre acetylcholine receptor regulation, namely, CGRP, tetrodotoxin, and KCl and obtained results which demonstrate the full effectiveness of this way of application
The timing of activity is a regulatory signal during development of neural connections.
No full textIn PNS and CNS remarkable rearrangements occur soon after the connections are laid down in the course of embryonic life. These processes clearly follow the period of developmental cell death and mostly take place during the very beginning of postnatal life. They consist in changes of the peripheral fields of neurons, marked by elimination of many inputs, while others undergo further maturation and strengthening. Along the efforts to uncover the signals that regulate development, it turned out that while the initial construction of the circuits is heavily based on chemical cues, the subsequent rearrangement is markedly influence by activity. Here we describe experiments testing the influence on developmental plasticity of a particular aspect of activity, the timing of nerve impulses in the competing inputs. Two recent investigations are reviewed, indicating strikingly similar developmental features in quite different systems, neuromuscular and visual. A sharp contrast between the effects of synchrony and asynchrony emerges, indicating that Hebb-related activity rules are important not only for learning but also for development
Hebb-based rules of neural plasticity: are they ubiquitously important for the refinement of synaptic connections in development?
No full textNeuronal death and suppression of functional synaptic inputs are well-known regressive events characterizing PNS and CNS development. In the CNS, participation of activity in synapse elimination has been known ever since the pioneering studies of Hubel and Wiesel, but only recently has a Hebb-based mechanism of spike synchrony versus asynchrony received unequivocal experimental support in the visual system. At the neuromuscular junction (NMJ), where synapse elimination was discovered, the specific function of the "timing of activity" was addressed by only one group of studies and did not receive widespread attention. Here we critically review the latest NMJ investigation advocating an "activity-independent" mechanism for synapse elimination and contrast it with an equally recent study demonstrating a key role for spike timing. Finally, we highlight how the striking similarities between the two mentioned studies on spike timing (visual system and NMJ) establish conclusively its role in the development of the nervous system in general
Spike timing plays a key role in synapse elimination at the neuromuscular junction.
No full textNerve impulse activity produces both developmental and adult plastic changes in neural networks. For development, however, its precise role and the mechanisms involved remain elusive. Using the classic model of synapse competition and elimination at newly formed neuromuscular junctions, we asked whether spike timing is the instructive signal at inputs competing for synaptic space. Using a rat strain whose soleus muscle is innervated by two nerves, we chronically evoked different temporal spike patterns in the two nerves during synapse formation in the adult. We found that asynchronous activity imposed upon the two nerves promotes synapse elimination, provided that their relative spikes are separated by 25 ms or more; remarkably, this elimination occurs even though an equal number of spikes were evoked in the competing axons. On the other hand, when spikes are separated by 20 ms or less, activity is perceived as synchronous, and elimination is prevented. Thus, in development, as in adult plasticity, precise spike timing plays an instructive role in synaptic modification
Activity-dependent vs neurotrophic modulation of acetylcholine receptor expression: evidence from rat soleus and extensor digitorum longus muscles confirms the exclusive role of activity
No full textEvoked electrical muscle activity suppresses the transcription of mRNAs for acetylcholine receptors in extrajunctional myonuclei. Muscle denervation or disuse release such inhibition and extrajunctional receptors appear. However, in soleus muscles paralyzed with nerve-applied tetrodotoxin, a restricted perijunctional region has been described where myonuclei remain inhibited, a finding attributed to nerve-derived trophic factor(s). Here, we reinvestigate extrajunctional acetylcholine receptor expression in soleus and extensor digitorum longus muscles up to 90 days after denervation or up to 20 days of disuse, to clarify the role of trophic factors, if any. The perijunctional region of soleus muscles strongly expressed acetylcholine receptors during the first 2-3 weeks of denervation. After 2-3 months this expression had disappeared. No perijunctional expression was seen after paralysis by tetrodotoxin or botulinum toxin A. In contrast, the extensor digitorum longus never displayed suppressed perijunctional acetylcholine receptor expression after any treatment, suggesting that it is an intrinsic property of soleus muscles. Soleus denervation only transiently removed the suppression, and its presence in long-term denervated soleus muscles contradicts any contribution from nerve-derived trophic factor(s). In conclusion, our results confirm that evoked electrical activity is the physiological factor controlling the expression of acetylcholine receptors in the entire extrajunctional membrane of skeletal muscles. This article is protected by copyright. All rights reserved
Use of dexamethasone with TTX block of nerve conduction shows that muscle membrane properties are fully controlled by evoked activity
No full textThis paper provides further evidence that motorneurons control extrajunctional properties of skeletal muscles through the activity evoked in the muscle fibres. The experiments compare the amount of action potential resistance to tetrodotoxin (TTX resistance) in denervated soleus muscle with that in soleus whose nerve was crushed and then allowed to regenerate in the presence of a block of the sciatic impulse conduction. Measurements were taken after about 2-3 weeks to allow full reinnervation and recovery of trophic regulation by the nerve. Blocking sciatic impulse conduction with TTX solutions containing low doses of the anti-inflammatory drug dexamethasone induced values of extrajunctional TTX resistance identical to those caused by denervation. In contrast lower levels of TTX resistance were obtained with dexamethasone-free solutions or when the drug was administered through the systemic path rather than topically applied to the nerve. These results indicate that physiological neural regulatory signals other than activity do not participate to the regulation of extrajunctional properties of skeletal muscles. Furthermore the low levels of TTX resistance measured with dexamethasone-free blocks confirm our previous experiments indicating that reported differences between denervation and pure inactivity are attributable to incomplete suppression of nerve impulse conduction
- …
