Sunday, September 25, 2016

9/26 VTA DA Neurons. Tye et al and Chaudhury et al

Summary of Tye et al:
In this study, they hypothesized that VTA DA neurons were involved in the neural circuit responsible for depression-like behaviors. The main findings were that 1) selectively inhibiting VTA DA neurons produces many depression-like behaviors, 2) the depression-like phenotype produced from CMS can be reversed with phasic activation of VTA DA neurons, 3) activation of NAc DA receptors are necessary to express baseline escape-related behavior, and 4) NAc neurons regulate escape-related behavior and phasic activation of VTA DA neurons. 

Questions/Comments for Tye et al:
Why did they use mice AND rats? During the electrophysiological portion of their study, they mentioned that the equipment was too cumbersome for mice and opted to use rats because their escape-related behavior wouldn't be affected as much. So now their neural representation data is from rats while the majority of their behavioral assays were performed on mice. They could have just used rats from the beginning. (In their defense, rats are likely more expensive to house, but that's the only reason I can think of that they'd use 2 different species)

I liked how in the conclusion, they included how other studies also using CMS show a decreased rate of DA neuron firing while studies that use social-defeat models (more severe stress) show an increased rate of firing; it just shows that they've looked at a wider assortment of studies that used different animal models that also looked at the link between depression-like symptoms and DA neurons.

Summary of Chaudhury et al:
In this study, they also looked at VTA DA neurons but instead focused on VTA DA neuron firing rate/firing type, 2 different VTA pathways (NAc and mPFC), and used a social-defeat model instead of CMS paradigm. They hypothesized that increased phasic firing of VTA DA neurons produced a depressive-like (susceptible) phenotype in mice when exposed to social-defeat stress, specifically the VTA-NAc pathway. The main findings were that 1) only phasic firing of VTA DA neurons produced depressive-like behavior in the social interaction and sucrose preference tests, 2) phasic firing of VTA DA neurons changed previously resilient mice to the susceptible phenotype, 3) activation of DA neuronal phasic firing in the VTA-NAc pathway produce susceptibility while inhibition of DA phasic firing in the same pathway produces resilience (the effects of activation/inhibition of DA phasic firing in the VTA-mPFC are reversed).

Questions/Comments for Chaudhury et al:
I'm not really sure how I feel about the social interaction test. I've never really liked the idea of it as an indicator of depression-/anxiety-like/avoidance behaviors. I understand why they'd use it though since they're also using the social-defeat model. The bar graphs for the social interaction tests (specifically Fig 1e, 2c, and 3c) show that when there's no other mouse in the cage, all 3 groups approach the interaction zone with the same frequency. When another mouse IS present, only the eYFP (phasic) and CHr2 (tonic) groups show a significant increase in time spent in the interaction zone. The CHr2 (phasic) mice, however, spend the same amount of time in the interaction zone whether a mouse is present or not. If the amount of time spent in the interaction zone was significantly LESS when a mouse IS present, then I would agree that it's a reliable indicator of avoidance behavior. 

In general, I don't think I was really "sold" on this paper. Toward the end, they claimed "Our study establishes a direct link between VTA DA-neuronal firing patterns and susceptibility to a depression-related phenotype", to which I responded with eyebrow-raising. 

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