Development and Specification of Cortical Layer 1 Microcircuits
Learning, attention, and fine motor movement are all complex tasks that require key brain circuits to compute multiple sensory information, gate the relevant signals internally, and finally create feedback loops to constantly adjust output pathways. In the mammalian neocortex, layer 1 (L1) interneurons are central to these circuits, where highly diverse populations of interneurons receive specific inputs from different synaptic partners to form robust circuit functions. As such, defects in L1 interneuron development and functions are key features in neurodevelopmental and psychiatric diseases, including intellectual disabilities, autism and schizophrenia. In this project, my goal is to understand how these specific L1 networks are formed during development. I hypothesize that different L1 interneurons mature at different rates, being this highly coordinated with the synaptic inputs from their afferent sources. I will test this model by studying the timing of maturation and input arrival of two L1 subpopulations, neurogliaform cells and α7 cells. I will also elucidate the molecular mechanism needed for functional maturation by performing scRNAseq at various developmental stages. Finally, I will use a genetic approach to perturb the maturation of L1 interneurons and determine the consequences in L1 circuits. Collectively, I will unravel how synaptic specificity is generated in L1 and how this contributes to normal brain circuit formation and to neurodevelopmental disorders.