Homer1a-dependent recovery from depression-like behavior by photic stimulation in mice.

A significant number of depressed people are resistant to drug therapy. Promising alternative therapy may be brain stimulation achievable by diverse methods. In a mouse model of depression, we previously investigated the mechanisms by which repetitive transcranial magnetic stimulation (rTMS) reverses depression-like behavior, and found an essential involvement of the immediate early gene product Homer1a. Home1a is known to be expressed not just by rTMS but also by photic stimulation (PS) via activation of the retino-geniculo-cortical pathway, suggesting that PS may have an antidepressant effect. This was tested by using a two-phase version of forced swimming (FS), in which the first phase consists of a 10-min swimming for 5 consecutive days and the second phase takes place at a 4-week interval for testing behavior. During the 4-week period, PS was applied everyday (300lx, 2Hz for 6h daily). After the last swimming, the brains were removed and subjected to quantitative RT-PCR and electrophysiological analysis. The 4-week-long PS alleviated depression-like behavior to the extent comparable to that obtained with rTMS previously. Homer1a expression was drastically reduced by FS and recovered by PS. Consistently with our previous studies, activity of the large conductance calcium-activated potassium (BK) channel was facilitated by PS in a Homer1a-dependent manner. PS may thus have a potential utility for depression therapy. Furthermore, given that Homer1a is implicated in various neuropsychiatric disorders, brain stimulations that induce Homer1a expression, such as rTMS or PS, may have a wider applicability than currently thought.