The Development and Integration of Early Born SST-Expressing Interneurons in the Cortex

Project Summary In this grant we propose three aims focused on exploring the following: (Aim 1) Determine the efferent target selectivity of granular and infragranular SST cINs and determine the developmental strategy by which this is achieved. (Aim 2) Explore the developmental molecular and cellular basis by which SST cIN diversity is generated. (Aim 3) Identify and validate the SST prototypes during late embryonic and early developmental periods that give rise to the nine SST cIN cell types that populate the mature cortex. A chief goal of my laboratory is to determine cortical interneuron diversity contributes selectively to cortical function and how perturbations in these programs result in brain disease. This grant is an exemplar of the multidisciplinary approaches that has become our hallmark and combines individuals with skills ranging from molecular biology, transcriptomic analysis, genetics and physiology. By combining these with the Fishell laboratory's expertise in development, genetics and circuit formation, we will explore in this proposal how developmental programs in SST cINs shape them selective synaptic connectivity. Together, this grant represents a broad scale effort to both develop and test the proposition that cortical circuits are much more precisely crafted such that the bewildering diversity we have discovered in excitatory and inhibitory neurons reflects a level of circuit organization that we are only beginning to understand. From our preliminary data it is evident that canonical cortical circuits are much more precise and specific to particular subtypes. By defining their relationships, as well as the molecular mechanisms that dictate their synaptic specificity, this work will greatly increase both our understanding of cINs, as well as the microcircuits they contribute to. This in turn will greatly extend our understanding of how discrete cIN and pyramidal neurons interact in the obligate lock and key mechanisms that allow their assembly.