Genetic Methods for Anatomical Analysis of Neuronal Circuits

An integral part of neural circuit analysis involves understanding cellular-level connectivity. With recent technical advances, this capability has finally been realized. In this chapter, we will discuss various methods of targeting specific cell types in transgenic mice, with an emphasis on the minimal promoter transgenic design. Minimal promoter transgenics is a “modular” transgenic approach in which a “driver” (i.e., a Cre or transactivator) line is crossed to different “payload” (i.e., floxed or tetO) lines to obtain region- and/or cell-specific patterns of transgenic expression. We will describe how this technique, when combined with the recombinant rabies viral tracer developed by Wickersham and colleagues (Nat Methods 4:47–49, 2007), enables the determination of monosynaptic inputs of specific cell types in the brain.