Cholinergic disinhibition in area CA1 of the rat hippocampus is not mediated by receptors located on inhibitory neurons.

We studied the effects of carbamylcholine (carbachol; CCh) on monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV). CCh (30 microM) blocked late afterhyperpolarizations but did not depress GABAA receptor-mediated fast monosynaptic IPSPs or GABAB receptor-mediated late monosynaptic IPSPs. In the presence of CCh the GABAB receptor agonist (+/- )-baclofen (2 microM) reversibly hyperpolarized pyramidal neurons and depressed monosynaptic IPSPs as under control conditions. Phorbol-12,13-diacetate (PDAc; 10 microM) increased fast and depressed late monosynaptic IPSPs, and prevented depression of IPSPs by baclofen. These results suggest that cholinergic disinhibition in area CA1 of the hippocampus results from decreased synaptic excitation of inhibitory neurons.