Muscarinic Suppression of Excitatory Synaptic Responses in Layer II of the Entorhinal Cortex

Entitled: Muscarinic suppression of excitatory synaptic responses in layer II of the entorhinal cortex and submitted in partial fulfillment of the requirements for the degree of Masters of Psychology complies with the regulations of the University and meets the accepted standards with respect to originality and quality. The entorhinal cortex is thought to play a role in mechanisms mediating sensory and mnemonic function, but the effects of acetylcholine on the strength of sensory cortical inputs to the entorhinal cortex are not well understood. We have previously shown that field excitatory postsynaptic potentials (fEPSPs) in the medial entorhinal cortex evoked by stimulation of the piriform cortex are suppressed during theta activity in behaving animals, and that cholinergic agonism suppresses fEPSPs in vivo. In addition, intracellular recordings from neurons in layer II of the entorhinal cortex also show a suppression of EPSPs in response to the cholinergic agonist carbachol. Here, we have used in vitro field potential recordings evoked by stimulation of layer I afferents to investigate the transmitter receptors that mediate the cholinergic suppression of synaptic responses in layer II of the medial entorhinal cortex. Ten-min bath-application of the cholinergic agonist carbachol (10 µM) potently suppressed the amplitude of fEPSPs. Carbachol also enhanced the paired-pulse facilitation ratio for EPSP amplitudes (30 ms interpulse interval), indicating that the cholinergic suppression is likely due to inhibition of transmitter release. Constant bath application of the M 2 receptor blocker methoctramine (5 µM) for 20 min prior to addition of carbachol did not prevent the cholinergic suppression, but application of the M 1 receptor blocker pirenzepine (1 µM) almost completely blocked the carbachol-induced suppression, indicating that the cholinergic suppression of excitatory synaptic responses in the entorhinal cortex is iv dependent primarily on activation of M 1 –like receptors. In addition to enhancements in neuronal excitability that follow cholinergic activation, therefore, cells in the superficial layers of the entorhinal cortex also display a suppression of excitatory synaptic input that is mediated mainly by M 1 muscarinic receptors.