The role of acetylcholine in learning and memory is explored, highlighting its importance in encoding new memories. Pharmacological studies show that muscarinic and nicotinic acetylcholine receptors play crucial roles in this process. Localized lesions and antagonist infusions have identified the anatomical locations where these cholinergic effects occur, and computational modeling links these effects to specific cellular mechanisms within these regions. Acetylcholine enhances encoding by increasing the strength of afferent input relative to feedback, contributing to theta rhythm oscillations, activating intrinsic mechanisms for persistent spiking, and enhancing synaptic modification. These effects may be particularly important in the entorhinal and perirhinal cortices and the hippocampus for encoding new episodic memories. The article discusses how these cellular mechanisms underlie the role of acetylcholine in memory encoding, including the enhancement of afferent input, regulation of inhibition, modulation of theta rhythm, and enhancement of persistent spiking. Future research should combine local pharmacological manipulations with physiological recordings to further understand the role of cholinergic modulation in memory processes.The role of acetylcholine in learning and memory is explored, highlighting its importance in encoding new memories. Pharmacological studies show that muscarinic and nicotinic acetylcholine receptors play crucial roles in this process. Localized lesions and antagonist infusions have identified the anatomical locations where these cholinergic effects occur, and computational modeling links these effects to specific cellular mechanisms within these regions. Acetylcholine enhances encoding by increasing the strength of afferent input relative to feedback, contributing to theta rhythm oscillations, activating intrinsic mechanisms for persistent spiking, and enhancing synaptic modification. These effects may be particularly important in the entorhinal and perirhinal cortices and the hippocampus for encoding new episodic memories. The article discusses how these cellular mechanisms underlie the role of acetylcholine in memory encoding, including the enhancement of afferent input, regulation of inhibition, modulation of theta rhythm, and enhancement of persistent spiking. Future research should combine local pharmacological manipulations with physiological recordings to further understand the role of cholinergic modulation in memory processes.