Acetylcholine inhibition in the intact and chronically isolated cerebral cortex.

1. Some spontaneously firing cells in the cerebral cortex of cats can be depressed by iontophoretically applied acetylcholine or acetyl-beta-methylcholine, and this depression is antagonized by atropine. Thirteen per cent of 101 spontaneously active neurones tested were depressed by cholinergic agents and 64% were excited.2. Single stimuli applied to the adjacent cortical surface excited 132 neurones orthodromically. Acetylcholine or acetyl-beta-methylcholine depressed this synaptic firing in 18% of the cells. The depression was blocked by atropine.3. The population of neurones in which cholinergic agents depressed spontaneous or synaptic firing was located within the superficial half of the cortex.4. Glutamate-induced firing was depressed by cholinergic agents in 41% of 211 cells tested; atropine and strychnine strongly antagonized this depressant action, while dihydro-beta-erythroidine was a weaker antagonist.5. Long duration inhibition of glutamate-induced firing evoked by repetitive stimulation of the cortical surface could be blocked by atropine or strychnine in both the intact and chronically isolated cortex. This provides strong evidence for a system of intracortical cholinergic neurones which make direct inhibitory contacts with neurones in the superficial layers of the cortex.