REPROGRAMMING OF INTERNEURON IDENTITY AS A MECHANISM FOR CORTICAL INHIBITORY PLASTICITY

Neuronal circuits exhibit remarkable plasticity early in life, undergoing extensive rewiring in response to sensory input. While plasticity in excitatory neurons is well-characterized, how inhibitory interneurons, essential for cortical balance and computation, adapt during this period remains poorly understood. This project investigates somatostatin-expressing (SST⁺) interneurons in the mouse cortex, which regulate the balance between bottom-up sensory and top-down predictive inputs. These include Martinotti cells (MCs), which target distal dendrites to modulate top-down signals, and non-Martinotti cells (nMCs), which influence sensory input via proximal dendrites. Our preliminary data reveal that overexpressing a single gene, ID2, postnatally reprograms MCs into nMCs, demonstrating a fate switch in post-mitotic neurons and uncovering unexpected flexibility in inhibitory cell fate. We aim to define the developmental window and molecular mechanisms underlying this fate plasticity, and assess the impact on neural activity and behavior. This work will uncover a novel mechanism of inhibitory circuit plasticity, reshape our understanding of cortical development, and inform new strategies to enhance plasticity or restore function in neurodevelopmental disorders.