week 2 optogenetics regulating depressive-like behaviors

I thoroughly enjoyed this week’s two articles significantly more than last week’s articles, perhaps due to the style of writing required by the Nature journal or that both papers are relatively new coming out in the year 2012. The article by Tye et al. clearly explained their study design and addressed other factors that might contribute or invalidate known results. They addressed that depression can be caused by stressors over time so they not only conducted acute stress tests on normal (not initially stressed) mice but also on mice that were exposed to a chronic mild stress paradigm. They even clearly stated that, “various stressors can lead to adverse responses from VTA neurons depending on pre-exposure and severity.” In their study design, they first proved that there was an induction of depressive-like behavior, such as despair and anhedonia, in normal mice that had their VTA neurons inhibited by illumination (the eNpHR3.0 mice model) in both the inescapable stressor tests and the sucrose-preference tests. Then, they did the same tests on CMS mice and showed that phasic illumination of VTA dopamine neurons reversed depressive-like behavior. To me, this finding was amazing and shows that different stressors have different effects on the brain’s circuitry!

The article by Chaudhury et al. also adequately showed that optogenetics can be used to understand the relationship between VTA neurons and depressive symptoms. I appreciated that the Chaudhury et al. article tested the difference of tonic and phasic firing in VTA dopamine neurons because this was something I had wondered while reading the Tye et al. article, what would be the effect of tonic firing in the VTA dopamine neurons? This article also recognized that VTA neurons fire differently based on the severity of stress. While chronic stress inhibits the activity of the VTA dopamine neurons, higher severity stimulus increases the activity of these neurons.

With two papers coming out at the exact same time both discussing how VTA dopamine neurons play a huge role in both producing and reversing depression related behaviors, I believe that this is a breakthrough in understanding the underlying circuits of depression. Better understanding of a disease’s etiology and pathology leads to more effective treatment.