Regulation of Intrinsic Plasticity in Neural Circuits

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The public health and economic impact of the cognitive effects of chronic sleep deprivation have grown enormously with the increasingly global and 24 hour nature of our society, and costs are in the billions. In spite of this, however, we know very little about the mechanisms by which sleep influences memory circuits. Memory formation is bidirectionally sensitive to sleep levels. Sleep in the temporal window following training can enhance formation of memory, while sleep deprivation has negative effects on its formation. In addition, learning has been shown to enhance sleep drive, suggesting that there are intrinsic mechanisms to promote sleep during memory formation. In Drosophila, we have a very detailed understanding both of the processes that underlie memory formation and sleep circuits. This proposal leverages this knowledge to understand, for the first time at a cellular level, the direct links between memory and sleep systems. In Aim 1 we will dissect the organization and functionality of co-transmission in the DPM neurons, a cell type critical for both long-term memory formation and learning-dependent sleep. These cells release multiple transmitters and understanding how these transmitters are deployed in the circuit will be important for understanding their functions. In Aim 2 we probe the regulation and plasticity of co-transmitter release in DPM. We hypothesize that target-selective release of the two transmitters imposes differences in the timing and amplitude of signals which will have profound effects on computations in the circuit. In Aim 3 we ask how co-transmission affects circuit dynamics. The core challenge we face today in our understanding of sleep and memory formation is to understand the dynamics of the circuit. In this aim we use functional imaging to map the temporal relationships in the MB circuit and the role of DPM in their regulation. Understanding this the cellular mechanisms of DPM function will provide important principles that will lead to the design of strategies to combat the negative cognitive effects of sleep deprivation.