Optogenetics

The two papers that were examined this week by Tye et al (2012) and Chaudhury et al (2012), both explored the role of the ventral tegmental area (VTA) and the nucleus accumbens in the brain's response to a variety of stressful conditions. In the Tye et al (2012) paper, the effects of optogenetically activating or inhibiting neurons in the VTA were explored using a chronic mild stress paradigm. Upon optogenetic activation of the VTA neurons, the depressive symptoms instilled in the mice as a result of stressful situations such as the tail-suspension test and the forced swim test were reversed. In addition, mice that were exposed to chronic mild stress and then subjected to the sucrose preference test showed significantly more preference for sucrose when the VTA neurons were optogenetically activated. The reverse was also true, in that mice with optogenetically inhibited VTA neurons displayed significantly more depressive like symptoms. Tye et al (2012) also found that dopamine receptors in the nucleus accumbens of mice trigger the activation of VTA neurons.

            In the Chaudhury et al (2012) paper, the firing rates of the VTA neurons, as well as the effects of optogenetic activation versus inhibition, were more closely examined as a focal point of the research. Interestingly, Chaudhury et al (2012) found that activation of VTA neurons after social defeat stress triggered depressive-like symptoms, while inhibition alleviated these symptoms and allowed for the mice to be “resilient.” They also found that activation of phasic firing in the VTA neurons led to the depressive-like symptoms observed, whereas tonic firing did not yield the same results. Similarly to Tye et al (2012), they found that the nucleus accumbens is primarily responsible for the circuitry that accounts for depressive behaviors, as opposed to other brain regions.

            The differences in results between Chaudhury et al (2012) and Tye et al (2012) may be because of the different types of stress tests they used. Tye et al used a chronic mild stress paradigm, while Chaudhury used the social defeat stress paradigm. This difference in the methods of the experiments could account for the different results obtained by the two papers.