During adolescence, many high-order cognitive functions develop and mature, including impulse control, long-term planning, and risk evaluation. Neurological disorders that impair executive function, such as schizophrenia, are often diagnosed during adolescence. One major site of adolescent maturation in prefrontal cortex are GABAergic inhibitory circuits, including parvalbumin positive chandelier cells. Chandelier cells synapse directly onto the axon potential initiating sites of neighboring glutamatergic pyramidal cells. They are therefore uniquely poised to regulate pyramidal cell spiking. Here, our goal is to understand how chandelier cells regulate the activity of pyramidal cells as prefrontal cortical networks undergo adolescent development. We will use a combination of electrophysiology, including perforated patch recording, 2-photon imaging and genetic techniques to understand how these unique interneurons regulate the integrative properties of the axon initial segment. Results of this study will provide insight into how inhibitory circuit maturation contributes to the normal maturation of prefrontal circuits and may elucidate potential therapeutic targets in neurological disorders such as schizophrenia.
This work focuses on the role of GABAergic inhibitory inputs, specifically chandelier cell inputs, in developing prefrontal circuits. Chandelier cells are thought to regulate large prefrontal cortical networks that undergo a high degree of refinement and maturation during adolescence. Understanding how chandelier cells regulate pyramidal cell networks may lead to new therapeutic approaches for disorders that disrupt prefrontal cortex function and impair executive function, including schizophrenia.
| Rinetti-Vargas, Gina; Phamluong, Khanhky; Ron, Dorit et al. (2017) Periadolescent Maturation of GABAergic Hyperpolarization at the Axon Initial Segment. Cell Rep 20:21-29 |
