Both Tye and Chaudhury used optogenetics to investigate the relationship between phasic firing of dopaminergic neurons in the VTA. The biggest area of overlap in their research was the decision to concentrate on VTA dopaminergic neurons that project to the NAc. Tye et al. determined that VTA to NAc dopaminergic innervation is important in reversing the depressive-like symptoms brought about by chronic mild stress. Interestingly enough, Chaudhury et al. seemed to come to the reverse conclusion, stating that optical induction of phasic firing in the VTA-NAc neurons induced the susceptible phenotype (this is characterized by social avoidance and reduced sucrose preference).
There are a couple of differences in their methods that may have accounted for the opposing conclusions. Tye et. al induced depressive-like symptoms in mice by using the CMS paradigm, as well as the tail suspension test, the forced swim test, and the sucrose preference test. One thing I loved about this paper was that they thought to administer an open field test as well, to make sure that the reason for more or less struggling during the TST and FST was not a change in locomotor activity induced by the activation or inhibition of the VTA. On the other hand, Chaudhury used something known as the social defeat stress paradigm in concert with the sucrose preference test and the social-interaction test.
Although it looks like the two papers have completely different findings, I think that further research could possibly validate them both. While the CMS paradigm is a mild stressor (and a better animal model of depression, in my opinion), the social-defeat stress paradigm is more severe. It may be possible that dopaminergic innervation of the NAc is beneficial during less intense stress, and detrimental during harsher stress. Chaudhury mentions that chronic mild stressors inhibit VTA activity, whereas severe stressors increase VTA activity, so it makes sense that the ideal amount of VTA activity differs based on the type of stress. I am interested in seeing how other projections from dopaminergic neurons in the VTA can mediate the stress response. More specifically, I am curious to know what Tye would have observed had they investigated the VTA-mPFC pathway, like Chaudhury did.
There are a couple of differences in their methods that may have accounted for the opposing conclusions. Tye et. al induced depressive-like symptoms in mice by using the CMS paradigm, as well as the tail suspension test, the forced swim test, and the sucrose preference test. One thing I loved about this paper was that they thought to administer an open field test as well, to make sure that the reason for more or less struggling during the TST and FST was not a change in locomotor activity induced by the activation or inhibition of the VTA. On the other hand, Chaudhury used something known as the social defeat stress paradigm in concert with the sucrose preference test and the social-interaction test.
Although it looks like the two papers have completely different findings, I think that further research could possibly validate them both. While the CMS paradigm is a mild stressor (and a better animal model of depression, in my opinion), the social-defeat stress paradigm is more severe. It may be possible that dopaminergic innervation of the NAc is beneficial during less intense stress, and detrimental during harsher stress. Chaudhury mentions that chronic mild stressors inhibit VTA activity, whereas severe stressors increase VTA activity, so it makes sense that the ideal amount of VTA activity differs based on the type of stress. I am interested in seeing how other projections from dopaminergic neurons in the VTA can mediate the stress response. More specifically, I am curious to know what Tye would have observed had they investigated the VTA-mPFC pathway, like Chaudhury did.
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