DIFFUSE TRANSMISSION BY ACETYLCHOLINE IN THE CNS

Citation
L. Descarries et al., DIFFUSE TRANSMISSION BY ACETYLCHOLINE IN THE CNS, Progress in neurobiology, 53(5), 1997, pp. 603-625
Citations number
289
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
03010082
Volume
53
Issue
5
Year of publication
1997
Pages
603 - 625
Database
ISI
SICI code
0301-0082(1997)53:5<603:DTBAIT>2.0.ZU;2-O
Abstract
Recent immunoelectron microscopic studies have revealed a low frequenc y of synaptic membrane differentiations on ACh (ChAT-immunostained) ax on terminals (boutons or varicosities) in adult rat cerebral cortex, h ippocampus and neostriatum, suggesting that, besides synaptic transmis sion, diffuse transmission by ACh prevails in many regions of the CNS. Cytological analysis of the immediate microenvironment of these ACh t erminals, as well as currently available immunocytochemical data on th e cellular and subcellular distribution of ACh receptors, is congruent with this view. At least in brain regions densely innervated by ACh n eurons, a further aspect of the diffuse transmission paradigm is envis aged: the existence of an ambient level of ACh in the extracellular sp ace, to which all tissue elements would be permanently exposed. Recent experimental data on the various molecular forms of AChE and their pr esumptive role at the neuromuscular junction support this hypothesis. As in the peripheral nervous system, degradation of ACh by the prevale nt G(4) form of AChE in the CNS would primarily serve to keep the extr asynaptic, ambient level of ACh within physiological limits, rather th an totally eliminate ACh from synaptic clefts. Long-lasting and widesp read electrophysiological effects imputable to ACh in the CNS might be explained in this manner. The notions of diffuse transmission and of an ambient level of ACh in the CNS could also be of clinical relevance , in accounting for the production and nature of certain cholinergic d eficits and the efficacy of substitution therapies. (C) 1997 Elsevier Science Ltd.