Experience and sleep-dependent synaptic plasticity: from structure to activity

Abstract

Synaptic plasticity is important for learning and memory. With increasing evidence linking sleep states to changes in synaptic strength, an emerging view is that sleep promotes learning and memory by facilitating experience-induced synaptic plasticity. In this review, we summarize the recent progress on the function of sleep in regulating cortical synaptic plasticity. Specifically, we outline the electroencephalogram signatures of sleep states (e.g. slow-wave sleep, rapid eye movement sleep, spindles), sleep state-dependent changes in gene and synaptic protein expression, synaptic morphology, and neuronal and network activity. We highlight studies showing that post-experience sleep potentiates experience-induced synaptic changes and discuss the potential mechanisms that may link sleep-related brain activity to synaptic structural remodelling. We conclude that both synapse formation or strengthening and elimination or weakening occur across sleep. This sleep-dependent synaptic plasticity plays an important role in neuronal circuit refinement during development and after learning, while sleep disorders may contribute to or exacerbate the development of common neurological diseases. This article is part of the Theo Murphy meeting issue 'Memory reactivation: replaying events past, present and future'.

Keywords: dendritic calcium spike; dendritic spine; rapid eye movement sleep; replay; slow-wave sleep; synaptic plasticity.

Figure 1.

Sleep promotes dendritic spine remodelling associated with motor learning. (a) New spines are formed on different sets of dendritic branches of layer V pyramidal neurons in the motor cortex in response to different motor learning tasks. This sleep-dependent, branch-specific formation of dendritic spines facilitates the maintenance of new spines when multiple tasks are learned [10]. (b) REM sleep prunes and balances the number of newly formed spines during development and after learning. Concurrently, REM sleep also strengthens and maintains a subset of new spines that are critical for neuronal circuit development and performance improvement after learning [14]. REMD, REM sleep deprivation. (c) NREM sleep promotes new synapse formation after motor learning by reactivating task-related neurons [10], while REM sleep selectively eliminates and maintains newly formed synapses via dendritic calcium (Ca²⁺) spike-dependent mechanisms [14].

Figure 2.

Functional and structural changes of neocortical neurons across different brain states. A cartoon model depicting the wake/learning and sleep states and their associated subcellular and cellular activities across the cortical column. Under learning conditions, apical tuft dendrites of layer V pyramidal neurons receive task-specific dendritic spine activation (green spines on black dendritic shaft) and generate NMDAR-dependent, local calcium spikes (green spines and green dendritic shaft). Local spikes serve to modulate task-specific synapses (i.e. potentiate or depotentiate), summate with synaptic potentials across other dendritic branches and drive the somatic activity of pyramidal neurons (up activity arrows). GABAergic interneurons, such as layer I (L1; orange) interneurons, somatostatin-expressing (SST; blue) and parvalbumin-expressing (PV; purple) interneurons, promote or attenuate these synaptic potentials and local calcium events, thus regulating information flow within the cortical circuit. During post-learning NREM sleep, apical tuft synapses repetitively activate (green spines) and trigger branch-specific new spine formation over hours (pink spines). New spine formation occurs largely in the absence of local spikes. In REM sleep, a surge of acetylcholine (not depicted) and further dampening of SST-expressing interneuron activity (down activity arrows) promote local calcium spike generation (green spines and shaft) and thus create a high plasticity state in the apical tuft that is ‘disconnected’ from somatic output due to perisomatic PV-mediated inhibition (up activity arrows). Increased apical tuft calcium spikes function to stabilize new spines and eliminate others (red X adjacent to pink spine). Rehearsal (repetition of a learned behaviour) triggers reactivation of task-specific spines and further stabilizes newly formed spines (growth of pink spine). Pre-existing spines with the help of new spines can contribute to continued calcium spike generation, synaptic plasticity and improved performance of a learned skill. Important state-related synaptic events emphasized with red text. Key to activity arrows, dendritic spine and branch activities, and cell types displayed on the bottom of the figure.