Development of dendritic signal processing in the brain: a role for GABAergic interneurons?

Adolescence is a fundamental period for the successful emergence of higher brain functions, such as working memory and attention. It is also a period of heightened sensitivity for many mental health disorders, including schizophrenia, anxiety, and depression. Understanding adolescent changes in brain structure and function is therefore of major significance for society if we want to ensure that as many people as possible undergo healthy transitions from adolescence to adulthood.

This project will focus on understanding the maturation of higher-order brain circuits during adolescence, helping to uncover key signalling mechanisms and cell types that contribute to normal circuit formation. Classically, it has been proposed that the brain matures in a hierarchical manner, following the path of sensory information as it is relayed from the external world through different brain structures before finally reaching the prefrontal cortex, which matures during adolescence.

Much less is known about the development of projections travelling in the reverse direction, from the prefrontal cortex to lower-order sensory structures. To answer this question, the successful candidate will apply a wide range of in vitro and in vivo tools for neural circuit analysis. Using a cutting-edge combination of transgenic mice, two-photon calcium imaging and slice electrophysiology this project will map the cellular changes associated with the formation of top-down circuitry during adolescence.

To directly test the causal role of key cell types and circuits in adolescent circuit refinement, we will then employ genetic tools to selectively silence different neuronal populations throughout adolescence and measure the functional effect on the network.