Efficacy of the VTA-mPFC pathway test in Chaudhury et al.

In Chaudhury et al. there were multiple experiments looking at the different effects of exciting and inhibiting two different pathways that are known to be involved in dopamine release and depression. From the references (19) it somewhat seemed that the group wanted to follow up on the idea that there are “unconventional” dopamine neurons that have “high-frequency firing” to the mPFC. The VTA-mPFC pathway was not easy to find online, but we know that the VTA is the source of dopamine, and the mPFC may be involved in memory consolidation (please correct me if I’m wrong!). So, when I was reading about the group manipulating this pathway, a question came to mind about how important context memory is in this experiment. If the group were worried about memory consolidation, maybe they would use a paradigm (like the water maze task?) to just rule out the effect of inhibition/excitation on the consolidation.

            The next thing I thought about was the results of the inhibition/excitation paradigm. As we saw, the VTA-mPFC excitation showed no induction of susceptibility but with the inhibition, we saw that it promoted susceptibility but by only one (significant) measure. Chaudhury noted that there was a trend in “time in corner” yet it is not significant; therefore we are not sure how reliable. Since only 1/3 of the tests were significant, this makes me wary that it is enough to call this “promoted susceptibility”. If we’re going that far, we can almost say that it looks like there is a trend that excitation of the VTA-mPFC pathway makes mice more likely to explore, as they seem to be spending more time in the interaction zone and less time in the corner when a target is involved in tonic excitation. Since this pathway is still a mystery, I think this paper ends on a note that there is definitely more to be discovered about what happens when we manipulate the VTA-mPFC dopamine neurons and the other interactions it has in the brain.