week 2

Although both papers employ the use of optogenetic tools to understand the dopaminergic circuitry involved in depression, I find myself preferring Tye’s paper to Chaudhary’s for several reasons. For starters, I am not entirely convinced that social defeat is the only or perhaps the most efficient way to induce depression-like symptoms. “Chronic mild stress and chronic social-defeat stress have been shown recently to produce different changes in extracellular levels of several neurotransmitters in a number of brain areas18. These findings raise the possibility that, in addition to context, the severity of stress is another important determinant of stress regulation of dopamine-neuron firing.” If this is true, Chaudhary et al. could have used an additional paradigm or other “severe ” or “less severe” tests to compare the effects or strengthen the conclusion proposed. In contrast, Tye et al. employ the use of various tests and use the CMS model, which I believe (and I maybe wrong) is a better approach in inducing stress in the animal. Therefore, I found Tye’s approach to be more in depth and meticulous, whereas Chaudhary’s approach felt more superficial – even though they did explore additional downstream pathways (VTA-mPFC).

I also found it interesting that even though both these papers are investigating the firing pattern of the same neurons in a “stressful” paradigm, the results seem to outline complete contradictory interactions. Tye’s paper highlights how “selective inhibition of VTA dopamine neurons acutely produces depression-related behaviour in measures of both motivation and anhedonia, and that phasic activation of VTA dopamine neurons acutely rescues a chronic mild stress- induced depression-like phenotype, in a phenomenon that requires functioning of dopamine receptors in the NAc. Whereas Chaudhary’s paper found that “functional importance of increased phasic, but not tonic, firing of  VTA dopamine neurons during exposure to stress for promoting susceptibility for depression-like behavioural abnormalities.” I’m not sure if this difference may be due to using different paradigms or experimental protocol (days exposed to stressor), or perhaps an entirely different factor altogether, but I’m curious to find out!