Contribution of muscarinic M1 receptors to the cholinergic suppression of synaptic responses in layer II of the entorhinal cortex

The entorhinal cortex is thought to play roles in sensory and mnemonic function, and the cholinergic suppression of the strength of synaptic inputs is likely to have important impacts on these processes. Field excitatory postsynaptic potentials (fEPSPs) in the medial entorhinal cortex evoked by stimulation of the piriform cortex are suppressed during theta EEG activity in behaving animals, and cholinergic receptor activation suppresses synaptic responses both in vivo, and in layer II entorhinal neurons in vitro. Here, we have used in vitro field potential recordings to investigate the transmitter receptors that mediate the cholinergic suppression of synaptic responses in layer I inputs to layer II of the medial entorhinal cortex. Bath-application of the cholinergic agonist carbachol suppressed the amplitude of fEPSPs with an EC50 of 5.3 mu M, and enhanced paired-pulse ratio. The M-2/M-4 preferring receptor blocker methoctramine, or the M-4 receptor blocker PD102807, did not prevent the cholinergic suppression. However, the M-1/M-4 receptor blocker pirenzepine and the M-1 receptor blocker VU0255035 reduced the suppression, suggesting that the cholinergic suppression of synaptic responses in the entorhinal cortex is dependent in large part on activation of M-1 receptors. (C) 2013 Elsevier Ireland Ltd. All rights reserved.