Summary Sleep is thought to consolidate changes in synaptic strength, but the underlying mechanisms are unknown. We investigated the cellular events involved in this process in ocular dominance plasticity (ODP) - a canonical form of in vivo cortical plasticity triggered by monocular deprivation (MD) and consolidated by sleep via undetermined, activity-dependent mechanisms. We find that sleep consolidates ODP primarily by strengthening cortical responses to non-deprived eye stimulation. Consolidation is inhibited by reversible, intracortical antagonism of NMDA receptors (NMDARs) or cAMP-dependent protein kinase (PKA) during post-MD sleep. Consolidation is also associated with sleep-dependent increases in the activity of remodeling neurons, and in the phosphorylation of proteins required for potentiation of glutamatergic synapses. These findings demonstrate that synaptic strengthening via NMDAR and PKA activity is a key step in sleep-dependent consolidation of ODP.

Recent findings in humans and animals suggest that sleep promotes synaptic plasticity, but the underlying mechanisms have not been identified. We have demonstrated recently an important role for sleep in ocular dominance (OD) plasticity, a classic form of in vivo cortical remodeling triggered by monocular deprivation (MD) during a critical period of development. The mechanisms responsible for the effects of sleep on OD plasticity are unknown but may depend on neuronal activity in the sleeping brain. We investigated the role of cortical activity in sleep-dependent plasticity by reversibly inactivating the sleeping visual cortex (V1) after a period of MD. Critical period cats were bilaterally implanted with cannulas in V1 and standard EEG/EMG electrodes for polysomnographic recording. After a period of MD, visual cortices were infused with the sodium channel blocker lidocaine in vehicle or vehicle only during sleep. A third group of cats served as sham controls and were infused with lidocaine outside of V1 (into the CSF). Both optical imaging of intrinsic cortical signals and microelectrode recordings showed that OD plasticity was significantly reduced in cats whose visual cortices were reversibly silenced during sleep. These findings demonstrate that the mechanisms governing this form of sleep-dependent plasticity require cortical activity. They provide an important insight into how sleep modifies synaptic circuitry by narrowing the range of possible candidate mechanisms to those that are activity dependent.

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To examine the influence of conditioned fear stimuli on sleep-wake states, we recorded sleep in Sprague-Dawley rats after exposure to tones previously paired with footshock. After habituation to a recording chamber and the recording procedure, a baseline sleep recording was obtained the next day. One day later, experimental animals were exposed to shock training designed to induce conditioned fear (FC), consisting of five tone-footshock pairings. The 5-s tones (conditioned stimuli; CS) co-terminated with 1-s footshocks (unconditioned stimuli; US). The next day sleep was recorded for 4 h in the recording chamber after presentation of five CSs alone. Sleep efficiency (total sleep time/recording period) and REM sleep (REM) and non-REM (NREM) measures were determined. While sleep efficiency was not significantly changed after CS presentation, the percentage of total sleep time spent in REM (REM percentage) was reduced in the FC animals. The reduction in REM percentage in the FC animals was due to a decrease in the number of REM bouts. In a separate experiment, we repeated the procedures, except the tones and shocks were presented in an explicitly unpaired (UP) fashion. The next day, presentation of the tones increased REM percentage in the UP group. Results are discussed in terms of the decreases in REM as a response to conditioned fear, and the relevance of these findings to the sleep changes seen in post-traumatic stress disorder (PTSD).