Circuit Interactions of Adult-Born Neurons

The anterior/ventral dentate gyrus is a key gateway for mood regulation and stress responsiveness in humans and rodents. It contains a population of immature neurons throughout adulthood, providing a substrate for brain plasticity responsive to diverse physiological and pathological experiences. An extensive rodent literature establishes adult neurogenesis as a key factor for stress resilience, with independent lines of research corroborating the idea that young dentate neurons contribute to stress responsiveness by modifying the excitability of surrounding neurons. Yet the fundamental circuit mechanisms that underlie the interactions between new and older dentate neurons and how these interactions are affected by agents that enhance stress resilience are unclear. The goal of this project is to test a new mechanism to explain disparate ideas about how adult-born neurons modulate the excitability of the ventral dentate gyrus. Combining electrophysiological and pharmacological approaches along with anatomical labeling of synaptic circuits, we will determine how neurogenesis plays a modulatory role in the ventral dentate circuit and how ketamine affects the circuit interactions of adult-born neurons. Completion of the proposed experiments will reveal novel mechanisms underlying the contribution of adult neurogenesis to dentate excitability and stress responsiveness, potentially identifying new targets for treating stress-related mood disorders.