The effects of VTA-DA neurons - Dana Walker


Tye et al. and Chaudhury et al. both focused on the different roles of dopamine neurons in the VTA and how they affect depressive behaviors, but their varying methods presented differing results. Both also packed numerous experiments into one publication. Tye’s study manipulated VTA neurons expressing TH with eNpHR3.0/eYFP to hyperpolarize neurons upon illumination, as well as with ChR2/eYFP to excite them. Mice were either exposed or not exposed to a chronic mild stress (CMS) paradigm over 8-12 weeks. They found that phasic inhibition of VTA DA neurons resulted in an increase in depressive-like symptoms in the CMS group, and firing of these same neurons reversed these effects. Next, they collected recordings of the NAc and observed increased kicks during the forced swim task (FST) while stimulating VTA neurons. However, the role of these neurons can vary, as some responded to and some were inhibited by light.
Chaudhury took a slightly different approach. They only used ChR2, but investigated both tonic and phasic firing in VTA DA neurons. Their protocol was also a subthreshold exposure to social defeat. They found mice who experienced phasic stimulation showed an increase in depressive-like symptoms vs. controls and tonic stimulation. This introduced a new effect of DA from the VTA: one that rapidly and negatively affects behavior, as opposed to a positive effect. This effect is also capable of immediately converting phenotypically resilient mice to susceptible mice. Next, they compared the roles of the VTA-NAc and VTA-mPFC pathways in promoting resilient or susceptible phenotypes. They found these pathways have opposite effects; the VTA-NAc pathway can induces anhedonia, but not the VTA-mPFC pathway. Therefore, their article highlighted the different dopaminergic pathways from the VTA and how they both can play a role in depressive behaviors.
I appreciated that Chaudhury dove deeper into the different pathways from the VTA and their implications in depressive behavior. It became difficult to navigate the paper since they seemed to swap back and forth between subthreshold and repeat stressor paradigms. Perhaps better formatting within the paper or more figures outlining the procedures would have aided in separating the different experiments.
In Tye’s paper, I appreciated them breaking up the analysis into specific behaviors (anhedonia and motivation.) They also explicitly outlined different experiments using eNpHR3.0 and ChR2. It made the paper’s logic easier to follow. I also found a couple aspects of their research unique and memorable. I was interested in why the sucrose-preference test was measured using number of licks on spouts, instead of volume of water consumed. I wondered if this could possibly lead to confounds in measurements if mice drink differing amounts of water at different times.

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