Remembering and forgetting in sleep: Selective synaptic plasticity during sleep driven by scaling factors Homer1a and...

Sleep is a conserved and essential process that supports learning and memory. Synapses are a major target of sleep function and a locus of sleep need. Evidence in the literature suggests that the need for sleep has a cellular or microcircuit level basis, and that sleep need can accumulate within localized brain regions as a function of waking activity. Activation of sleep promoting kinases and accumulation of synaptic phosphorylation was recently shown to be part of the molecular basis for the localized sleep need. A prominent hypothesis in the field suggests that some benefits of sleep are mediated by a broad but selective weakening, or scaling-down, of synaptic strength during sleep in order to offset increased excitability from synaptic potentiation during wake. The literature also shows that synapses can be strengthened during sleep, raising the question of what molecular mechanisms may allow for selection of synaptic plasticity types during sleep. Here I describe mechanisms of action of the scaling factors Arc and Homer1a in selective plasticity and links with sleep need. Arc and Homer1a are induced in neurons in response to waking neuronal activity and accumulate with time spent awake. I suggest that during sleep, Arc and Homer1a drive broad weakening of synapses through homeostatic scaling-down, but in a manner that is sensitive to the plasticity history of individual synapses, based on patterned phosphorylation of synaptic proteins. Therefore, Arc and Homer1a may offer insights into the intricate links between a cellular basis of sleep need and memory consolidation during sleep.