Neuromodulation: acetylcholine and memory consolidation.

By Michael E. Hasselmo. 1999

Clinical and experimental evidence suggests that hippocampal damage causes more severe disruption of episodic memories if those memories were encoded in the recent rather than the more distant past. This decrease in sensitivity to damage over time might reflect the formation of multiple traces within the hippocampus itself, or the formation of additional associative links in entorhinal and association cortices. Physiological evidence also supports a two-stage model of the encoding process in which the initial encoding occurs during active waking and deeper consolidation occurs via the formation of additional memory traces during quiet waking or slow-wave sleep. In this article I will describe the changes in cholinergic tone within the hippocampus in different stages of the sleep-wake cycle and will propose that these changes modulate different stages of memory formation. In particular, I will suggest that the high levels of acetylcholine that are present during active waking might set the appropriate dynamics for encoding new information in the hippocampus, by partially suppressing excitatory feedback connections and so facilitating encoding without interference from previously stored information. By contrast, the lower levels of acetylcholine that are present during quiet waking and slow-wave sleep might release this suppression and thereby allow a stronger spread of activity within the hippocampus itself and from the hippocampus to the entorhinal cortex, thus facilitating the process of consolidation of separate memory traces.

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Citations in the corpus

Born to Learn: the Inspiration, Progress, and Future of Evolved Plastic Artificial Neural Networks (2017, background): “…variety of neural functions, from arousal and behavior (Harris-Warrick and Marder, 1991; Hasselmo and Schnell, 1994; Marder, 1996; Katz, 1995; Katz and Frost, 1996), to pattern generation (Katz et al., 1994), to memory consolidation (Kupfermann, 1987; Hasselmo, 1995; Marder, 1996; Hasselmo, 1999).”
About sleep's role in memory. (2013, background): “[Adapted from Hasselmo (520), with permission from Elsevier.”
Synaptic Mechanisms of Memory Consolidation during Sleep Slow Oscillations (2016, background): “Indeed, the low cholinergic activation, such as during SWS, permits information flow from the hippocampus to the neocortex (Hasselmo, 1999).”
A computational principle for hippocampal learning and neurogenesis (2005, background): “Hasselmo has suggested a mechanism by which the HPC could switch in and out of an acquisition/encoding mode, through the action of the neuromodulator acetylcholine (ACh) (see e.g., Hasselmo, 1999).”
Dissociable correlates of recollection and familiarity within the medial temporal lobes. (2004, background): “Given the role of acetylcholine in enhancing synaptic plasticity (Gu, 2002) and memory consolidation (Hasselmo, 1999), we have hypothesized that an orbitofrontal-rhinal circuit may act to modulate the encoding of items based on their relative novelty or distinctiveness (Kishiyama & Yonelinas, in…”
Slow-wave sleep takes the leading role in memory reorganization (2010, background): “Low acetylcholinergic tone, which occurs during SWS, is a further prerequisite for such transfe”
Complementary Learning Systems (2014, background): “…Hasselmo and colleagues have explored various ways in which the hippocampal system could dynamically switch between encoding and retrieval modes (Hasselmo, 1999; Hasselmo, Bodelon, & Wyble, 2002; Hasselmo, Schnell, & Barkai, 1995; Molyneaux & Hasselmo, 2002; Wyble, Linster, & Hasselmo, 2000).”
Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior. (2006, background): “Acetylcholine has been shown to suppress excitatory neurotransmission on proximal dendrites of hippocampal pyramidal cells in vitro, through presynaptic muscarinic receptors (Hounsgaard, 1978; Dutar and Nicoll, 1988; Hasselmo and Schnell, 1994; cf. Hasselmo, 1999).”
Memory consolidation. (2015, background): “Hasselmo (1999) argued that changes in the level of acetylcholine mediate the directional flow of information to and from the hippocampus.”
The role of acetylcholine in learning and memory. (2006, background): “These effects could alter cortical functional dynamics because acetylcholine levels change during waking and sleep [30].”
Graded persistent activity in entorhinal cortex neurons (2002, background): “Cholinergic muscarinic influences have been shown to be vital to memory processe”
Learning-Dependent Increases in Sleep Spindle Density (2002, background): “Regarding declarative memory consolidation, sleep may provide a state during which newly acquired memory contents, which are temporarily stored in the hippocampus, can be easily transferred to the neocortex for integration into long-term memories (Buzsaki, 1998; Hasselmo, 1999; Sutherland and McNaug”
Sleep for cognitive enhancement (2014, background): “Presenting one of the contextual odor cues again during subsequent sleep reduced fear responses to the face images in the next morning (Hauner et al., 2013).”