Optogenetics, physiology, and emotions

Optogenetics is a powerful tool for investigating causal links between neural circuits and behavior. In recent years, optogenetic studies have expanded into the emotional realm, elucidating new facts about the circuits that underlie anxiety, depression, and reward. One caveat with investigating this realm is that emotional responses can be non-linear. Reward is pleasurable to a point, beyond which it can produce mania, an anxious, and unpleasant state. Consistent with this, stimulant drugs that increase dopaminergic function are reinforcing across a limited dose range, above which they are no longer reinforcing, presumably because of anxiogenic effects (Ettenberg and Geist, 1991, 1993; Yang et al., 1992; Deroche et al., 1997). Many published optogenetic studies have not examined potential non-linearities in the relationship between neural activity and the behavior being studied, nor identified where on such a curve their optogenetic manipulation is acting. In addition, the state a neural system achieves during optogenetic stimulation may not necessarily reside on a physiological curve at all, as optogenetics can drive firing parameters outside of physiological ranges (Figure 1). We believe that further consideration of this point may lead to more accurate insights into the relationships between neural activity, emotions, and behavior.