Dopamine Neurons in the VTA and Depression

In these two papers, Tye et al. (2012) and Chaudhury et al. (2012) explored the role of the ventral tegmental area (VTA) and the nucleus accumbens (NAc) in the brain’s response to stress.  They both addressed how dopamine neurons in the VTA induced depression-like behavior in mice either by their stimulation or silencing.  The Tye et al. (2012) paper focused on determining the mechanism by which dopamine neurons cause depression.  On the other hand, Chaudhury et al. (2012) asked what type of firing in dopamine neurons caused depression.  Mice in the Tye et al. (2012) experiment expressed more escape-related behavior and increased sucrose preference when the VTA underwent phasic and optogenetic stimulation.  However, mice in the Chaudhury et al. (2012) experiment expressed the opposite behavior when the VTA underwent phasic stimulation.

The fact that Tye et al. (2012) used the chronic mild stress (CMS) model, whereas Chaudhury et al. (2012) used a model of social-defeat stress, makes it more difficult to compare the two experiments.  I also had trouble differentiating between what it meant to undergo optogenetic activation versus phasic activation.  I thought that the social-defeat stress test was very interesting as I think it well represents the antisocial characteristics of depressed people.  It was also interesting to learn more about how the pre-frontal cortex firing contributed to susceptible and resilient phenotypes in the mice.  I found the Tye et al. (2012) paper to be the more convincing of the two, especially because the chronic mild stress model is one of the most valid models of depression.  The authors were also more straightforward and helpful with their explanations. 

            I think that the next step would be to explore what other circuits cause the dopaminergic response to depression in the VTA.  Afterwards, researchers can perform more optogenetic techniques to better understand the reward-related dopamine circuit and to increase the number of active dopamine neurons in the VTA.  It might be good to look into when and how GABAergic neurons stimulate dopaminergic ones, and see how this might affect symptoms of depression.