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Principal Investigator: Ryohei Yasuda
Organization: MAX PLANCK FLORIDA CORPORATION
Fiscal Year: 2024
Award: $1,123,260
Funding agency: National Institute of Neurological Disorders and Stroke
Abstract
Dendritic spines are mushroom-shaped postsynaptic compartments that host intracellular
signaling cascades important for synaptic plasticity and, thereby, learning and memory. Signaling
events in spines involve a network composed of hundreds of proteins interacting with each other
extensively. Synaptic plasticity is typically induced by Ca2+ elevation in spines, which activates a
variety of signaling pathways. This leads to changes in the actin cytoskeleton and membrane
dynamics, which in turn causes structural and functional changes of the spine. Recent studies
have demonstrated that the activities of these proteins have a variety of spatiotemporal patterns,
which orchestrate signaling activity in different subcellular compartments at different time scales.
To better understand the operational principles of this network and the mechanisms underlying
plasticity, we will develop tools to optically measure and manipulate signaling activity in neurons
in both brain slices and in awake, behaving animals during plasticity. In particular, we aim to
develop innovative technology to image and measure endogenous proteins by combining
advanced imaging techniques, new optogenetic tools and genome-editing technology. Using
these tools, we will determine time windows of signaling activity mediated by endogenous
proteins, and elucidate how intracellular signaling mediates synaptic, circuit and behavioral
plasticity. This will thus lead to a better understanding of how information is processed at different
time scales and provide new insights into the molecular mechanisms underlying learning and
memory.
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