Of Mice, Men, and Microbial Opsins: How Optogenetics Can Help Hone Mouse Models of Mental Illness

Genetic, pharmacologic, and behavioral manipulations have long been powerful tools for generating rodent models to study the neural substrates underlying psychiatric disease. Recent advances in the use of optogenetics in awake behaving rodents has added an additional valuable methodology to this experimental toolkit. Here, we review several recent studies that leverage optogenetic technologies to elucidate neural mechanisms possibly related to depression, anxiety, and obsessive-compulsive disorder. We use a few illustrative examples to highlight key emergent principles about how optogenetics, in conjunction with more established modalities, can help to organize our understanding of how disease-related states, specific neuronal circuits, and various behavioral assays fit into hierarchical frameworks such as the National Institute of Mental Health Research Domain Criteria matrix.