Locus coeruleus modulation of sleep-induced insight gain.

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Abstract: The goal of this proposal is to elucidate how LC-NA promotes specific sleep features to directly facilitate insight gain. Sleep oscillations during NREM sleep have been identified that mediate memory updating and consolidation. LC noradrenergic neurons fire prior of slow waves, whereas LC becomes silent during spindle events all through NREM. A recent study from the Poe lab provided evidence that abnormal LC activity decreases sleep spindle density and affects memory consolidation. However, it is unclear how LC-NA activity gates sleep-dependent neural circuits to improve memory updating and temporal pattern recognition. Thus Aim 1 will use extracellular recordings, EGG/EMG and computational approaches to characterize LC noradrenergic activity patterns during sleep in animals that gain insight after a sleep period. Then in Aim 2 we will evaluate if LC noradrenergic activation or inhibition during sleep is essential to promote insight learning using optogenetic tools. Finally, in Aim 3 utilizing multi-structure extracellular recordings and optogenetic tools we will assess the effects of LC-NA projections to hippocampus (Hipp) and medial prefrontal cortex (mPFC). Taken together, the experiments to be performed in this proposal will provide valuable knowledge on how patterns of activity during sleep promote off-line mechanisms that allow for memory updating and provide novel therapeutic venues.