The development of cholinergic neurons.
Motoneuron precursors acquire some principles of their spatial organization early in their cell lineage, probably at the blastula stage. A predisposition to the cholinergic phenotype in motoneurons and some neural crest cells is detectable at the gastrula to neurula stages. Cholinergic expression is evident upon cessation of cell division. Cholinergic neurons can synthesize ACh during their migration and release ACh from their growth cones prior to target contact or synapse formation. Neurons of different cell lineages can express the cholinergic phenotype, suggesting the importance of secondary induction. Early cholinergic commitment can be modified or reversed until later in development when it is amplified during interaction with target. Motoneurons extend their axons and actively sort out in response to local environmental cues to make highly specific connections with appropriate muscles. The essential elements of the matching mechanism are not species-specific. A certain degree of topographic matching is present throughout the nervous system. In dissociated cell culture, most topographic specificity is lost due to disruption of local environmental cues. Functional cholinergic transmission occurs within minutes of contact between the growth cone and a receptive target. These early contacts contain a few clear vesicles but lack typical ultrastructural specializations and are physiologically immature. An initial stabilization of the nerve terminal with a postsynaptic AChR cluster is not prevented by blocking ACh synthesis, electrical activity, or ACh receptors, but AChR clusters are not induced by non-cholinergic neurons. After initial synaptic contact, there is increasing deposition of presynaptic active zones and synaptic vesicles, extracellular basal lamina and AChE, and postjunctional ridges over a period of days to weeks. There is a concomitant increase in m.e.p.p. frequency, mean quantal content, metabolic stabilization of AChRs, and maturation of single channel properties. At the onset of synaptic transmission, cell death begins to reduce the innervating population of neurons by about half over a period of several days. If target tissue is removed, almost all neurons die. If competing neurons are removed or additional target is provided, cell death is reduced in the remaining population. Pre- or postsynaptic blockade of neuromuscular transmission postpones cell death until function returns.(ABSTRACT TRUNCATED AT 400 WORDS)
Vaca
K
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Department of Neurology, Baylor College of Medicine, Houston, TX 77030.
D000818:Animals; D002454:Cell Differentiation; D002799:Cholinergic Fibers / Q000166:cytology / Q000502:physiology*; D009420:Nervous System / Q000166:cytology* / Q000196:embryology; D009424:Nervous System Physiological Phenomena