|Memory > Memory Retrieval: The Role of Acetylcholine|
The mind is restless. Even when you are alone, without any sensory inputs into your brain, the thoughts do not stop. Especially if you come back home from a date with a new girlfriend, the memorable memories still linger on. They may keep coming to your mind in the next few days whenever you are awake and quiet. This phenomenon is known as "hippocampal replay", that is, the previously activated hippocampal neurons are reactivated spontaneously, without any sensory inputs. It is basically a memory retrieving process in the absence of reminding cues. Acetylcholine (ACh) has been demonstrated to play an important role.
During hippocampal replay, the electroencephalography (EEG) exhibits "sharp wave ripples" (SWRs) which oscillate at the frequency between 110 and 200 Hz. SWRs can be induced by low ACh level whereas the high ACh level produces the theta rhythm (4 - 7 Hz) through complex mechanisms (Dannenberg et al., 2017).
Memory Retrieval by ACh
In the hippocampus, ACh is released primarily from the cholinergic fibers that originate in the medial septum/diagonal band of Broca (MSDB). ACh has five muscarinic receptors, M1 - M5, which belong to G protein-coupled receptors. Blockade of M1 has been shown to impair the retrieval of well-trained memory (Soma et al., 2014).
M1 receptors are highly expressed in the granule cells of dentate gyrus and the pyramidal cells of CA3 and CA1. Importantly, they are distributed preferentially on the extrasynaptic membrane of pyramidal cell dendrites and spines (Yamasaki et al., 2010), suggesting that their major targets are not located at synapses. Rather, ACh could regulate NMDA plateau. By acting on the M1 receptor, ACh may increase Ca2+ level, which in turn enhances PKA activity via AC1 (Figure 25-2). The enhanced PKA activity can then phosphorylates S1166 of GluN2B to recover NMDAR extinction, and consequently facilitating memory retrieval (Chapter 19).
Author: Frank Lee