Pharmacology of the dendritic action of acetylcholine and further observations on the somatic disinhibition in the rat hippocampus in situ

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In rats under urethane anaesthesia various cholinergic agonists and antagonists were microiontophoretically applied in the pyramidal layer of area CA1 and in the apical dendrites, using a twin set of multibarreled micropipettes. Thus, the somatic population spike and the dendritic negative field (field excitatorypostsynaptic potential) evoked by commissural stimulation and the effect of iontophoretic agents at either site were recorded simultaneously. Using this double recording system, several observations were made which confirmed the previous conclusions that acetylcholine has an important disinhibitory action at the level of the pyramidal cell bodies. Both muscarinic and nicotinic agents enhanced the somatic population spikes without altering the dendritic field excitatory postsynaptic potential. Local ejection of atropine, or scopolamine readily depressed or abolished the action of muscarinic agents (such as muscarine, metacholine or acetylcholine) without reducing the effects of nicotinic agents. Conversely, on several occasions, brief applications of curare or dihydro-β-erythroidine selectively reduced the effects of dimethylphenylpiperazinium or tetramethylammonium. Local applications of acetylcholine in the apical dendrites reduced the field excitatory postsynaptic potential and the somatic population spike recorded simultaneously. This effect was reproduced by muscarinic agents (notably muscarine or metacholine); in contrast nicotinic agents (notably dimethylphenylpiperazinium or tetramethylammonium) increased the field excitatory postsynaptic potential and the simultaneously recorded somatic spike. This effect had a slow onset and a maximal increase was observed toward the end of a 20 s application. These actions were pharmacologically specific since local ejection of scopolamine or atropine completely blocked the action of muscarinic agents whereas curare or dihydro-β-erythroidine selectively reduced the enhancement of the field excitatory postsynaptic potential produced by dimethylphenylpiperazinium or tetramethylammonium. In summary, both muscarinic and nicotinic receptors are involved in the facilitatory action of cholinomimetics at the cell soma, whereas muscarinic and nicotinic agents have an opposite actions on the dendritic field excitatory postsynaptic potentials.