Disruption of place cell remapping by scopolamine during aversive learning

Abstract

ABSTRACTWe performed in-vivo calcium imaging of hippocampal place cells in freely behaving rats (n=14) to investigate whether the muscarinic acetylcholine receptor (mAChR) antagonist scopolamine, which is known to impair aversive learning, also disrupts place cell remapping that occurs during such learning. CA1 neurons were imaged using a large-field-of view version of the UCLA miniscope (MiniLFOV) while rats performed a shock avoidance task on a rectangular maze. Drug-free avoidance training and extinction caused place cells to remap near the shocked location, in accordance with prior studies. Systemic pre-training injections of scopolamine (1 mg/kg) did not impair immediate shock avoidance, and also did not disrupt spatial tuning properties or shock-evoked responses of place cells during training. However, the drug impaired 48 h retention of avoidance and also prevented place cells from remapping near the shocked location. In addition, when rats navigated the maze on scopolamine, CA1 population vectors showed degraded between-session similarity with drug-free maze visits on prior days, suggesting that mAChR antagonism acutely degraded the fidelity with which stored hippocampal representations were retrieved. Based upon these results, we propose that scopolamine causes amnesia by degrading the dynamics of hippocampal memory retrieval at the population level, thereby shielding stored memory representations from being modified by experience to encode new memories of events that occur under the influence of the drug.