Mechanisms of Social Learning in Female Mice: The Roles of Estrogens and Muscarinic Acetylcholine Signaling

Abstract

Social learning is a common, adaptive learning strategy in animals and humans, in which an individual acquires information or skills from another in their social group. Despite its importance to human and animal learning, social learning has received relatively little research attention, and we thus are only beginning to understand the neurobiological mechanisms underlying this type of cognition. In this thesis, I investigated the roles of the rapid effects of estrogens and the effects of acetylcholine signaling at muscarinic receptors in short- and long-term memory for socially learned information using the Social Transmission of Food Preferences (STFP) task in mice, in which an observer mouse preferentially consumes a novel food that they had previously smelled on the breath of a conspecific demonstrator mouse. Estradiol rapidly (within 45 minutes) and activation of the G protein-coupled estrogen receptor 1 (GPER1) with the agonist G1 facilitate short-term STFP memory on the STFP when administered systemically. The first part of this thesis focuses on the brain regions in which estrogens may act to facilitate social learning. We therefore infused estradiol into the dorsal hippocampus and basolateral amygdala of female ovariectomized (OVX) mice. Second, we investigated muscarinic acetylcholine signaling as a possible downstream mechanism of estradiol and G1’s rapid facilitatory effects. We tested this by co-administering doses of estradiol or G1 previously found to facilitate STFP memory with a subeffective dose of the muscarinic receptor antagonist scopolamine before testing short-term STFP memory. Finally, we sought to determine which muscarinic receptor subtypes mediate the impairing effects of scopolamine on the STFP. We first tested the effects of scopolamine on long-term STFP memory in ovariectomized and gonadally intact female mice. We then tested the effects of the M1 antagonist dicyclomine and the M2 antagonist AF-DX 116 on long-term STFP memory. Through these investigations, we found that while estradiol did not facilitate short-term STFP memory when infused into the hippocampus or basolateral amygdala, it may facilitate short-term memory by enhancing acetylcholine at muscarinic receptors. Lastly, we found that muscarinic receptor signaling is also necessary for long-term STFP memory in gonadally intact female mice and that the M1 receptor subtype is one of the muscarinic receptors mediating this effect