Circuit and cellular mechanisms of adult neurogenesis in context encoding and discrimination

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Project summary The dentate gyrus subfield of the adult hippocampal formation exhibits a unique form of plasticity, the ability to generate new neurons throughout life. These adult born granule cells (abGCs) integrate into existing circuitry and have distinct properties during specific phases of their development. This process of adult neurogenesis is dynamically regulated by environment and emotional state; interventions that have negative effects on mood, such as stress and isolation can reduce levels of neurogenesis, while interventions that increase mood, such as enrichment and exercise can increase levels of neurogenesis. Behaviorally, these abGCs have been implicated in cognitive functions such as learning and memory, as well as mood related functions such as responses to stress or antidepressant treatment. However, we lack a complete understanding of the firing patterns of abGCs in freely behaving mice, how their dynamic encoding patterns differ from mature GCs (mGCs) and how environment may alter these activity patterns in vivo. Here we will address these long- standing questions in the field. Using novel, cutting-edge tools for monitoring and manipulating the activity of age-matched cohorts of abGCs in vivo, we will ask how these neurons contribute to hippocampal function during their development. First, we will use cell-type specific optical techniques to silence specific cohorts of these neurons during phases of context encoding and discrimination. Then we will use functional calcium imaging in freely moving mice to determine how abGCs function during these tests of context encoding and differentiation. Finally, we will determine how environmental enrichment and exercise alter the firing patterns and encoding properties of abGCs and the DG- CA3 circuit in vivo. The goal of these studies is to understand the mechanisms by which these neurons encode contextual representations during fear memory formation. Understanding the role of abGCs in this process may allow us to harness this unique form of plasticity in the adult brain for the treatment of fear and anxiety- related disorders.