Optogenetics to study the circuits of fear- and depression-like behaviors: a critical analysis

In recent years, the development and extensive use of optogenetics resulted in impressive findings on the neurobiology of anxiety and depression in animals. Indeed, it permitted to depict precisely the role of specific cell populations in various brain areas, including the amygdala nuclei, the auditory cortex, the anterior cingulate, the hypothalamus, the hippocampus and the bed nucleus of stria terminalis in specific aspects of fear and anxiety behaviors. Moreover, these findings emphasized the involvement of projections from the ventral tegmental area to the nucleus accumbens and the medial prefrontal cortex in eliciting depressive-like behaviors in stress-resilient mice or in inhibiting the expression of such behaviors in stress-vulnerable mice. Here we describe the optogenetic toolbox, including recent developments, and then review how the use of this technique contributed to dissect further the circuit underlying anxiety- and depression-like behaviors. We then point to some drawbacks of the current studies, particularly a) the sharp contrast between the sophistication of the optogenetic tools and the rudimentary aspect of the behavioral assays used, b) the fact that the studies were generally undertaken using normal rodents, that is animals that have not been subjected to experimental manipulations shifting them to a state relevant for pathologies and c) that the opportunity to explore the potential of these techniques to develop innovative therapeutics has been fully ignored yet. Finally, we discuss the point that these findings frequently ignore the complexity of the circuitry, as they focus only on a particular subpart of it. We conclude that users of this cutting edge technology could benefit from dialog between behavioral neuroscientists, psychiatrists and pharmacologists to further improve the impact of the findings.