Toward a Genetic Dissection of Cortical Circuits in the Mouse

The mammalian neocortex gives rise to a wide range of mental activities and consists of a constellation of interconnected areas that are built from a set of basic circuit templates. Major obstacles to understanding cortical architecture include the diversity of cell types, their highly recurrent local and global connectivity, dynamic circuit operations, and a convoluted developmental assembly process rooted in the genome. With our increasing knowledge of gene expression and developmental genetic principles, it is now feasible to launch a program of genetic dissection of cortical circuits through systematic targeting of cell types and fate mapping of neural progenitors. Strategic design of even a modest number of mouse driver lines will facilitate efforts to compile a cell type parts list, build a Cortical Cell Atlas, establish experimental access to modern tools, integrate studies across levels, and provide coordinates for tracing developmental trajectory from circuit assembly to functional operation.