Linking Network Activity to Synaptic Plasticity during Sleep: Hypotheses and Recent Data

Abstract

Research findings over the past two decades have supported a link between sleep states and synaptic plasticity. Numerous mechanistic hypotheses have been put forth to explain this relationship. For example, multiple studies have shown structural alterations to synapses (including changes in synaptic volume, spine density, and receptor composition) indicative of synaptic weakening after a period of sleep. Direct measures of neuronal activity and synaptic strength support the idea that a period of sleep can reduce synaptic strength. This has led to the synaptic homeostasis hypothesis (SHY), which asserts that during slow wave sleep, synapses are downscaled throughout the brain to counteract net strengthening of network synapses during waking experience (e.g., during learning). However, neither the cellular mechanisms mediating these synaptic changes, nor the sleep-dependent activity changes driving those cellular events are well-defined. Here we discuss potential cellular and network dynamic mechanisms which could underlie reductions in synaptic strength during sleep. We also discuss recent findings demonstrating circuit-specific synaptic strengthening (rather than weakening) during sleep. Based on these data, we explore the hypothetical role of sleep-associated network activity patterns in driving synaptic strengthening. We propose an alternative to SHY—namely that depending on experience during prior wake, a variety of plasticity mechanisms may operate in the brain during sleep. We conclude that either synaptic strengthening or synaptic weakening can occur across sleep, depending on changes to specific neural circuits (such as gene expression and protein translation) induced by experiences in wake. Clarifying the mechanisms underlying these different forms of sleep-dependent plasticity will significantly advance our understanding of how sleep benefits various cognitive functions.

Phagocytic elimination of synapses by microglia during sleep

“…Thus, about 20% of synapses or synaptic activity may be lost during sleep. Although the molecular and cellular mechanisms have not been well understood (Puentes-Mestril & Aton, 2017), this study presents a series of evidence supporting that microglial cells eliminate synapses through phagocytosis during sleep.…”

Sleep promotes downward firing rate homeostasis

“…The synaptic homeostasis hypothesis (SHY) proposes that wakefulness drives learning-related increases in synaptic strengths and FRs, while sleep renormalizes activity by down-regulating synaptic strengths, a process dependent on activity patterns during NREM sleep (Tononi and Cirelli, 2014). A combination of structural, electrophysiological and molecular evidence has been put forward in support of SHY (de Vivo et al, 2017;Vyazovskiy et al, 2008;Vyazovskiy et al, 2009;Liu et al, 2010;Diering et al, 2017), but contradictory data have also been reported (Yang et al, 2014;Chauvette et al, 2012;Aton et al, 2014;Durkin and Aton, 2016), and in some cases the interpretation of these findings has been questioned (Frank, 2012;Frank and Cantera, 2014;Timofeev and Chauvette, 2017;Puentes-Mestril and Aton, 2017). In particular, it has been unclear whether sleep and wake cause global oscillations in firing rates under baseline conditions, when animals have not experienced a dramatic plasticity or learning event.…”

Neural memory of the genioglossus muscle during sleep is stage‐dependent in healthy subjects and obstructive sleep apnoea patients

“…The mechanisms responsible for the link between increased genioglossus memory and SWS are still largely unknown. Most of the previous literature related to the effects of SWS on synaptic plasticity investigated forebrain mechanisms, which probably cannot be translated to the brainstem given the deeply different networks in which these circuits are embedded (Huber et al 2004;Chauvette et al 2012;Puentes-Mestril & Aton, 2017).…”

“…Other causes are related to circuit mechanisms involving feedback loops and changes in the balance of inhibitory and excitatory inputs (Zucker & Regehr, ; Tadjalli et al . ; Puentes‐Mestril & Aton, ). These various mechanisms may play a role in the development of stable breathing during SWS by increasing genioglossus activity.…”

“…For example, it can be produced by 'synaptic plasticity' , which adjusts the synaptic strength between respiratory neurons based on their previous activity. Other causes are related to circuit mechanisms involving feedback loops and changes in the balance of inhibitory and excitatory inputs (Zucker & Regehr, 2002;Tadjalli et al 2010;Puentes-Mestril & Aton, 2017). These various mechanisms may play a role in the development of stable breathing during SWS by increasing genioglossus activity.…”