Connecting Synaptic Plasticity, Neural Circuits, and Behavior

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Experience-dependent changes in behavior rely upon the reshaping of neural networks through synaptic plasticity. For this reason, synaptic plasticity is evolutionarily conserved and contributes to virtually all non- instinctive behavioral patterns. Despite its importance and intense study, a substantial gap remains in our knowledge of how synaptic plasticity reshapes patterns of neural activity to achieve behavioral changes. For instance, the transcription factor CREB contributes to plasticity that underlies memory formation in rodents, fruit flies, sea slugs, and worms, but the specific mechanisms that connect CREB to the synapse are unclear. This gap remains because it has not been possible to examine the cell biology of the synapse with single-cell resolution and simultaneously link these cell biological properties to behavior. In this proposal, I will address this gap in knowledge using the nematode C. elegans, a model organism uniquely suited to bridging molecular genetics, synaptic physiology, and neural circuit function. I have developed tools that allow me to move seamlessly in vivo between analyzing the consequences of genetic mutations on individual synaptic proteins in single neurons, measuring the impact on neurotransmission, and determining the consequences for experience-dependent behavior. I will use these tools to define how CREB modulates presynaptic function and neural circuit logic under conditions that lead to experience-dependent changes in temperature-associated migration behavior. The proposed studies will begin to close the gap between plasticity and neural circuit function in behavior. The pathways and genes that support plasticity are conserved across organisms and are important for diseases ranging from schizophrenia to substance abuse. For these reasons, this work will inform research in many different fields and holds the potential to identify novel targets for therapeutic interventions.