ReviewOf Mice, Men, and Microbial Opsins: How Optogenetics Can Help Hone Mouse Models of Mental Illness
Section snippets
Obsessive-Compulsive Disorder
Evidence from both humans and animals reveals that the repetitive and compulsive behaviors characteristic of OCD reflect dysfunction in cortico-striato-thalamocortical circuitry (20). Specifically, hyperactive connectivity between the orbitofrontal cortex (OFC) and striatum has been implicated as an important circuit mechanism underlying compulsive/repetitive behavior (21, 22). Moreover, reversal of hyperactivity in this circuit is associated with treatment response in humans (23). According to
Depression
Attempts to model depression in rodents rely on many behavioral assays, each capturing potentially overlapping components of the disease (e.g., forced swim or tail suspension tests for motivated behavior, sucrose preference test for anhedonia) (29, 30, 31). Optogenetics has accelerated the identification of precise neural pathways mediating each of these phenotypes, which together contribute to the syndrome of depression. Optogenetic studies of depression have largely focused on manipulating
Anxiety
While both assays of innate anxiety, such as the open field test (OFT) and elevated plus maze (EPM), as well as conditioned fear paradigms, in which a conditioned stimulus is paired with an aversive unconditioned stimulus, are well established in the rodent literature, optogenetic manipulation of amygdala circuitry and its distal projections during these assays has added to our understanding of the circuitry that contributes to anxiety-like behavior (42, 43). While upstream amygdala circuitry
Conclusions
Here, we presented a few examples to show how optogenetics can elucidate the specific neural mechanisms underlying particular RDoC domains, as well as advance our understanding of these domains themselves. As these examples illustrate, optogenetic studies by no means supplant studies of transgenic or mutant animals. Rather, optogenetics can be most informative when combined with these approaches to probe how the function of particular neuronal pathways is altered by these manipulations.
Acknowledgments and Disclosures
This work was supported by a National Institutes of Health New Innovator Award to VSS, NIMH R01 MH100292, and the Staglin Family and International Mental Health Research Organization. TFM is additionally supported by an APF/Genentech Schizophrenia Research Fellowship.
Dr. Sohal receives research funding from F. Hoffmann-La Roche. Dr. Marton reports no biomedical financial interests or potential conflicts of interest.
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