The connection patterns of the billions of neurons in the mammalian brain underlie how neural circuits process information essential for perception, memory, and behavior. We have implemented viral-genetic tools that enable comprehensive mapping of input, output, and input–output relationships of specific neural types at the scale of the entire brain. Using these tools, we systematically map connection patterns of hypothalamic neurons underlying various social behaviors in mice. Specifically, we study anatomical differences in the neural circuit between male and female mice at the resolution of synaptic connection patterns, focusing on neurons that regulate sexual behaviors and reproduction. We also investigate the state-dependent circuit shift for parturition and lactation in female mice during pregnancy. These comparative connectomics approach will form a foundation upon which developmental and functional studies of neural circuits can be integrated in the future.

Currently, most genetic techniques in neuroscience are only applicable to mice, as Cre recombinase-dependent strategy is commonly used to regulate specific types of target neurons. To overcome this limitation, we combine CRISPR-mediated in situ gene knock-in and viral toolboxes to enable cell-type specific manipulations in non-model mammalian species without germline manipulation. We will then analyze organization and function of evolutionally orthologous neural circuits across mammalian species. This comparative connectomics will hopefully lead to an integrative platform for the study of evolution of neural circuits.