The consolidation of recent experiences into long-lasting memories is a fundamental function of the brain and essential for survival. Sleep has long been thought to be important for memory consolidation, and sleep deprivation has adverse consequences for cognitive function. Recent data suggest that sleep promotes the adaptive changes in connections between neurons which are thought to underlie memory formation. However, progress in understanding how sleep promotes these processes has been slow, due to the number and diversity of changes occurring simultaneously in the sleeping brain - including changes in neuronal firing patterns, intercellular signaling between neurons, and neuronal protein synthesis. The goal of the proposed research is to define which features of sleep are necessary and sufficient for a simple form of sleep-dependent memory consolidation - contextual fear memory. We will use recently-developed optogenetic and pharmacogenetic tools to manipulate neuronal activity in the sleeping brain in a cell type-specific manner. This will allow us to test whether features of network activity (e.g., low-frequency oscillations in hippocampal circuits) and neurotransmission (e.g., changes in noradrenaline and acetylcholine release) unique to the sleeping brain play a causal role in sleep-dependent memory formation. We will also use newly-developed molecular tools to profile active protein translation in specific cell types within the hippocampus during sleep- dependent memory consolidation. Finally, we will combine these tools to determine for the first time how sleep- associated changes in neuronal activity and neurotransmission impact intracellular processes such as protein translation in neural circuits.
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