Accumulating evidence suggests that neurogenesis continues in the adult mammalian hippocampus including that of humans, and is relevant for many cognitive behaviors. New neurons generated in the dentate gyrus area of the adult hippocampus mature into dentate granule cells and integrate into existing neural circuits. While adult born dentate granule cells (abDGCs) continue their morphological development for an extended period of time, there seems to be a transient maturation period when immature young abDGCs exhibit heightened membrane excitability and elevated synaptic plasticity. Recent studies through pharmacogenetics and optogenetic down regulation of adult neurogenesis have provided important insights on how a small population of abDGCs may exert specific behavioral influence, from spatial pattern separation to cognitive flexibility, and how different ionic currens may contribute to the unique biophysical properties observed during abDGCs critical maturation periods. However, it is largely unclear how adult neurogenesis influences DG neural network in vivo, and how changes in abDGCs' biophysical and synaptic properties during critical maturation period relate to their behavioral impacts. Recently, we developed a robust optogenetic platform capable of transiently silencing a set of age-defined abDGCs to bias behavior and to influence hippocampal neural network dynamics. We here will use this optogenetic platform to further analyze the neural network impacts of age-defined abDGCs on bilateral hippocampus. In addition, we will use the recently invented expansion microscopy technique to perform super-resolution anatomical characterizations of abDGCs' connectivity patterns relevant for their functional impacts. Upon completion of this study, we hope to provide a detailed, time resolved understanding of changes in the neural network connectivity patterns of abDGCs through maturation, and to advance our understanding of the functional significance of adult neurogenesis in physiology and pathology.

Public Health Relevance

The discovery of adult neurogenesis in the adult mammalian hippocampus, including humans, has raised significant interest in understanding the roles played by adult-born neurons in neural circuit functions, and in developing cell replacement therapies for neurological and psychiatric diseases. However, little is known about the causal role of adult neurogenesis in hippocampal functions. Here, we will perform a comprehensive time-resolved analysis of the functional connectivity pattern changes of hippocampal adult neurogenesis.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Neurobiology of Learning and Memory Study Section (LAM)
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Buhring, Bettina D
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Boston University
Engineering (All Types)
Biomed Engr/Col Engr/Engr Sta
United States
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