Acetylcholine and the cortical dynamics of encoding and consolidation

Hasselmo, M.

Boston University, Massachusetts, USA

The neuromodulator acetylcholine appears to play an important role in regulating the encoding and consolidation of episodic memories. Lesions studies indicate that episodic memories initially are vulnerable to hippocampal lesions, but this vulnerability decreases over time, leading to the proposal that consolidation results in formation of additional memory traces in the neocortex. Acetylcholine appears to set appropriate dynamics for the initial encoding of information in the hippocampus, as acetylcholine levels are high during active waking, enhancing the response of cortical neurons to external input and enhancing synaptic modification, while suppressing excitatory feedback (Hasselmo, 1999; Hasselmo, 2006). In contrast, acetylcholine levels show a dramatic decrease during quiet waking and slow-wave sleep resulting in substantial changes in cellular physiology. Low acetylcholine levels result in a reduced response to thalamic input, but an enhancement of excitatory cortical feedback that underlies generation of sharp wave/ripple events in the hippocampus that spread back to neocortex (Buzsaki, 1989). These sharp wave ripple events are associated with replay of sequences of spiking activity that occurred during previous behavior (Lee and Wilson, 2002). This replay could underlie the consolidation of episodic memory traces in neocortical structures. The proposed role of acetylcholine in regulating encoding and consolidation has been supported by behavioral tests showing impairments of encoding by blockade of acetylcholine receptors, reductions of consolidation by increased levels of acetylcholine and enhancement of consolidation by blockade of acetylcholine receptors (Rasch et al., 2006).

Buzsaki G (1989) Two stage model of memory trace formation: a role for "noisy" brain states. Neuroscience 31, 551-570.
Hasselmo ME. (1999). Neuromodulation: acetylcholine and memory consolidation. Trends Cogn Sci 3, 351-359.
Hasselmo ME. (2006). The role of acetylcholine in learning and memory. Curr Opin Neurobiol 16, 710-5.
Lee AK, Wilson MA (2002) Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36(6): 1183-1194.
Rasch BH, Born J, Gais S. (2006). Combined blockade of cholinergic receptors shifts the brain from stimulus encoding to memory consolidation. J Cogn Neurosci 18, 793-802.