Cholinergic modulation of memory in the basolateral amygdala involves activation of both m1 and m2 receptors

Abstract

Muscarinic cholinergic activation is a critical component of basolateral amygdala (BLA)-mediated modulation of memory consolidation. The receptor(s) mediating this activation during consolidation have not been elucidated. This study investigated the roles of muscarinic subtype 1 (m1) and subtype 2 (m2) receptors in memory enhancement, by post-training intra-BLA infusions of the non-selective muscarinic agonist oxotremorine. Rats received intra-BLA infusions of either oxotremorine alone (10 microg in 0.2 microl per side), oxotremorine together with the selective m1 antagonist telenzipine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with the selective m2 antagonist methoctramine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with a combination of the above doses of telenzipine and methoctramine, or only vehicle, immediately after inhibitory avoidance training. Performance on a 48-hour retention test was significantly enhanced in oxotremorine-treated rats relative to vehicle-infused controls. Intra-BLA co-infusion of oxotremorine with either telenzipine (5, 17 or 50 nmol/side) or methoctramine (17 or 50 nmol/side) blocked the oxotremorine-induced enhancement. Combinations of these antagonists did not act additively to block memory enhancement by oxotremorine. These findings indicate that modulation of memory consolidation induced by cholinergic influences within the BLA requires activation of both m1 and m2 receptor synapses. Plausible mechanisms for m1- and m2-mediated influences on BLA circuitry are discussed.