Memory  >   Memory Consolidation: Slow Oscillations Are Paced by Locus Coeruleus

A night's sleep consists of several 90-120 minute cycles, each is divided into four stages: N1, N2, N3 and REM, where "REM" stands for "rapid eye movement" and "N" for "non-REM" (NREM). At the N3 stage, the subject falls into deep sleep which in the electroencephalography (EEG) exhibits slow oscillations at the frequency between 0.2 and 4 Hz. Therefore, the N3 deep sleep is also known as slow wave sleep. The depolarizing and hyperpolarizing phases of the slow oscillation are referred to as UP and DOWN states, respectively (see Figure 7-2). While in the DOWN state, neurons are virtually silent. By contrast, the UP state represents a period of intense neural activity. Decades of intensive investigations have established that slow oscillations are crucial for memory consolidation.

In brain slices containing locus coeruleus (LC), the LC neurons display subthreshold oscillations at the frequency between 0.3 and 3 Hz (Christie et al., 1989; Alvarez et al., 2002), which matches the frequency range of slow oscillations. Moreover, LC neurons project to all memory storage areas, including prefrontal cortex, hippocampus, basolateral amygdala, and nucleus accumbens (Hansen, 2017, Figure 1; Ferrucci et al., 2013), which exhibit slow oscillations during slow wave sleep (Chapter 7). These results suggest that the slow oscillation could be paced by LC. Further evidence comes from the finding that LC neurons fire preferentially along the ascending edge of the slow oscillation, correlating with the DOWN-to-UP transition (Eschenko et al., 2012).


Figure 33-1. LC neurons project to all memory storage areas that exhibit slow oscillations. BLA: basolateral amygdala; NAc: nucleus accumbens (located in the striatum); PFC: prefrontal cortex; HPC:  hippocampus.

When NMDARs are in the resting state, the build-up of a substantial glutamate pond is sufficient to produce NMDA plateaus (Oikonomou et al., 2012). However, after learning, GluN2B-containing NMDARs are likely to enter an extinction state where the channel pore is occluded by the CABT complex. In this case, to produce NMDA plateaus, NMDARs should first recover from the extinction state. Although both norepinephrine (NE) and acetylcholine (ACh) may recover NMDAR extinction (Chapter 24 and Chapter 25), the NE released from LC neurons is superior to ACh for pacing the UP and DOWN states of slow oscillations (explained in Chapter 36).


Author: Frank Lee
First published: July, 2018