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Depression-Related Behaviors, Tye and Chaudhury

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Both Tye et al and Chaudhury et al saw robust results from activating and inactivating the VTA in depression-related behaviors. I think their findings are both elegantly done and contribute to a bigger story of the VTA and its involvement in mediating behaviors associated with depression. Tye et al show that by inhibiting VTA neurons after Chronic Mild Stress, depressive-like behaviors are induced. By activating the same subset of neurons, escape behaviors after CMS can be restored. Additionally, Tye et al showed that activation of the VTA in rats increases the prevalence of escape behavior in a novel stress test. Chaudhury et al utilize a different stress paradigm called the social defeat stress model. Their data indicate that phasic stimulation of the VTA causes depressive-liked behaviors in a social defeat paradigm, but inhibiting the VTA can restore social interaction in mice after they experience social defeat.

 Each paper explores related, yet different concepts. Although they come to different conclusions when activating and inactivating the VTA, I think the data are still complementary. While Tye et al mainly study stress models that display escape behavior, Chaudhury et al use a stress model that studies social interaction. Both behavioral paradigms are categorized under “Chronic Mild Stress,” yet they are testing two separate aspects that are seen in depression. The overlapping behavior test between the two papers, the sucrose-preference test, examines the anhedonic phenotype under two different conditions: social stress and learned helplessness. This could explain why they see differential results.

Chaudhury et al go a step further in studying the VTA by isolating specific projection routes of the VTA. While their data give great insight into how the VTA-NAc and VTA-mPFC circuits may modulate depressive-like behavior, it’s difficult to believe their interpretation of the results. This is because (a) they only studied male mice and (b) many other known outputs of the VTA are ignored. While their paper offers promising results for interpreting the functional importance of individual VTA circuits, I am still skeptical about there being other factors that may have led to the results they saw.

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