To explore the development and function of clonally-related adult-born dentate gr

State University New York Stony Brook, Stony Brook NY

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Abstract

DESCRIPTION (provided by applicant): The dentate gyrus of adult hippocampus continuously generates new granule cells. New granule cells integrate into the existing neural circuits and regulate hippocampal behaviors. In the aged animals, there is not only a substantial decrease in the generation of newborn granule cells but also increasing failure in circuit integration of these new neurons. This raises the importance of understanding the strategy for circuit integration of new neurons in the adult brain, which remains largely unknown. In one of our recent studies in collaboration with Dr. Dan's group, we found that clonally-related sister neurons in the developing cortex are initially synchronized. This suggests that new neurons may share similar properties during integration, and are co- activation during hippocampal function. This motivates us to establish a method to label and manipulate clonally-related newborn granule cells and study their neural circuit integration and activation. As an exploratory study, we will first characterize the development of clonally-related adult-born granule cells. We will perform dual patch clamp whole cell recording of clonally-related granule cells to test their neuronal and synaptic properties during development. Secondly, we will test whether clonally-related adult-born granule cells are preferentially co-activated during 2+ hippocampal activities. To achieve this goal, we will perform Ca and c-fos imaging to study the activation of clonally-related granule cells after they are fully integrated. Importantly, we will test whether the initial synchronizatio of clonally-related adult-born granule cells is required for their development and function. Additionally, using optogenetic method, we will test whether clonally-related new neurons are differentially activated by different laminar activation. Our finding will delineate whether clonaly-related newborn granule cells share a similar developmental track and preferentially recruited during hippocampal activities. We will also test whether the initial gap junction coupling is necessary to normal development and function of clonally-related newborn neurons. These studies will provide some basis for studying the generation and development of new neurons in the aged brain.