Cholinergic nerve terminals establish classical synapses in the rat cerebral cortex: Synaptic pattern and age-related atrophy

This study addresses the issue of whether cholinergic varicosities in the c erebral cortex establish 'classical synapses' or whether they communicate w ith their targets non-synaptically by 'volume transmission'. Most recent st udies in the neocortex have suggested that acetylcholine acts non-synaptica lly, however in the present study we provide ultrastructural evidence that suggests synaptic mechanisms prevail. This conclusion is based upon our ult rastructural observations that cholinergic boutons - as revealed by immunor eactivity for the specific cholinergic market, vesicular acetylcholine tran sporter - establish a high percentage of classical synapses in layer V of t he rat parietal cortex. Furthermore, the combination of this approach with the intracellular labeling of large pyramidal neurons on slice preparations revealed significant incidences of cholinergic, contacts abutting preferen tially on dendritic shafts. Finally, we have gathered information suggestin g that cholinergic boutons undergo atrophy with aging which could be relate d to the well-known cholinergic and cognitive decline. These results illustrate that the cholinergic terminations in the neocortex establish proper synaptic connections and that they experience important a ge-dependent atrophy. (C) 2001 IBRO. Published by Elsevier Science Ltd, All rights reserved.