Acetylcholine plays a critical role in learning and memory, particularly in encoding new memories. Both muscarinic and nicotinic acetylcholine receptors are involved in this process. Pharmacological studies show that blocking muscarinic receptors impairs memory encoding but not retrieval, while activating nicotinic receptors enhances encoding. Anatomical studies indicate that cholinergic effects are localized to specific brain regions, such as the entorhinal and perirhinal cortex and hippocampus, which are crucial for encoding episodic memories. Cholinergic modulation enhances memory encoding through several mechanisms. It increases the influence of afferent input relative to feedback, contributes to theta rhythm oscillations, activates intrinsic mechanisms for persistent spiking, and enhances synaptic modification. These effects are task-specific and vary across cortical structures. In the hippocampus, cholinergic modulation suppresses excitatory feedback synapses, reducing interference from previous retrieval and enhancing encoding. It also modulates inhibition and theta rhythm oscillations, which are essential for memory consolidation. Cholinergic activation enhances persistent spiking in cortical neurons, providing a mechanism for maintaining novel information in working memory and encoding into long-term memory. Acetylcholine also enhances long-term potentiation (LTP), a key mechanism for synaptic plasticity. Studies show that cholinergic modulation increases LTP in various brain regions, including the hippocampus, entorhinal cortex, and piriform cortex. This suggests that acetylcholine enhances memory formation by strengthening synaptic connections. Overall, research indicates that acetylcholine modulates cortical dynamics to support memory encoding and consolidation. Future studies should explore how cholinergic modulation affects the timing of action potentials relative to theta rhythm oscillations. The role of acetylcholine in learning and memory is increasingly supported by converging evidence from behavioral, anatomical, and computational studies.Acetylcholine plays a critical role in learning and memory, particularly in encoding new memories. Both muscarinic and nicotinic acetylcholine receptors are involved in this process. Pharmacological studies show that blocking muscarinic receptors impairs memory encoding but not retrieval, while activating nicotinic receptors enhances encoding. Anatomical studies indicate that cholinergic effects are localized to specific brain regions, such as the entorhinal and perirhinal cortex and hippocampus, which are crucial for encoding episodic memories. Cholinergic modulation enhances memory encoding through several mechanisms. It increases the influence of afferent input relative to feedback, contributes to theta rhythm oscillations, activates intrinsic mechanisms for persistent spiking, and enhances synaptic modification. These effects are task-specific and vary across cortical structures. In the hippocampus, cholinergic modulation suppresses excitatory feedback synapses, reducing interference from previous retrieval and enhancing encoding. It also modulates inhibition and theta rhythm oscillations, which are essential for memory consolidation. Cholinergic activation enhances persistent spiking in cortical neurons, providing a mechanism for maintaining novel information in working memory and encoding into long-term memory. Acetylcholine also enhances long-term potentiation (LTP), a key mechanism for synaptic plasticity. Studies show that cholinergic modulation increases LTP in various brain regions, including the hippocampus, entorhinal cortex, and piriform cortex. This suggests that acetylcholine enhances memory formation by strengthening synaptic connections. Overall, research indicates that acetylcholine modulates cortical dynamics to support memory encoding and consolidation. Future studies should explore how cholinergic modulation affects the timing of action potentials relative to theta rhythm oscillations. The role of acetylcholine in learning and memory is increasingly supported by converging evidence from behavioral, anatomical, and computational studies.