Stimulant-induced exocytosis from neuronal somata, dendrites, and newly formed synaptic nerve terminals in chronically decentralized sympathetic ganglia of the rat

Loss of preganglionic neurones underlies the autonomic failure of human mul tiple system atrophy. In rat sympathetic ganglia decentralization leads to new synapse formation. We explored whether these synapses are functional, a nd whether chronically decentralized neurones respond normally to activatio n, in terms of exocytosis. Potassium depolarization and cholinergic agonist s were applied to freshly excised rat superior cervical sympathetic ganglia , preganglionically denervated with prevented reinnervation 5 months earlie r. Ganglia were incubated and stimulated in the presence of tannic acid, wh ich stabilizes released vesicle cores for subsequent electron microscopy. I n denervated ganglia exocytosis was observed from newly formed synaptic ner ve terminals, and from nonsynaptic surfaces of neurone somata and dendrites , The results demonstrated that the new intraganglionic synapses, which are mostly catecholaminergic, can function and that chronically decentralized sympathetic neurones remain capable of stimulant-induced exocytosis from so mata and dendrites. The maximal release upon potassium depolarization did n ot differ significantly between denervated and contralateral ganglia. Relat ive to this, the exocytotic responses of decentralized somata and dendrites to nicotine resembled those of contralateral ganglia. Responses to muscari ne were significantly less in denervated than in contralateral ganglia, ind icating inhibition in dendrites. Responses to carbachol suggested interacti ons between nicotinic and excitatory muscarinic effects. Nerve terminals in denervated ganglia showed high basal release. Their responses to muscarine and carbachol resembled those of the decentralized neurones, from which mo st may originate. Their response to nicotine evidenced inhibition. Their ac tions, coupled with nonsynaptic effects of soma-dendritic exocytosis, might modulate responses of the decentralized neurone population to other surviv ing inputs. This modulation could be influential in disease-induced decentr alization in man. (C) 1999 Wiley-Liss, Inc.