Week 2: Tye and Chaudhury

The papers by Tye et al. and Chaudhury et al. both provide interesting research regarding the relationship between ventral tegmental area dopamine neuron activation and depressive behaviors. Both studies have a similar purpose looking into this relationship and use optogenetic techniques to observe and quantify the activation states of these specific VTA DA neurons. However, the procedures Chaudhury and Tye used were different and their conclusions were largely contrasting. Tye et al. concludes that the phasic activation of VTA DA neurons reverses depressive-like behaviors in stress-induced mice, specifically anhedonia and reduced motivation. The paper makes note that this effect is immediate and reversible as well, meaning that inhibition of the same dopaminergic neuronal projections to the VTA increases the depressive-like behaviors. On the other hand, Chaudhury et al. concludes that activation of the VTA dopamine neurons in a phasic neuronal pattern in stress-induced mice induces depressive-like behavior and that inhibiting the dopaminergic projections to the VTA reduces these behaviors. One explanation for these differing conclusions may due to their differing procedures.

 The studies both focus on the implementation and alleviation of depressive-like symptoms in stress-induced rodents but use different paradigms to implement the stress. Tye uses a chronic mild stress paradigm for 8-12 weeks while Chaudhury uses the social defeat paradigm. It is believed that the CMS is a gentler stress paradigm, which may have affected the level of stress induced and therefore the rodent’s response to alleviating efforts in the VTA DA neurons. Both studies used the sucrose preference test to test for anhedonia but Tye also used the Forced-Swim test while Chaudhury used the social interaction test to quantify other depressive behaviors. Although the researchers were probably limited by funds and time, it would be interesting to see the result of VTA DA activation and inhibition in regards to the many other symptoms of depression besides anhedonia, motivation, and social interaction. In humans, depression is a multifaceted disorder that is often hard to pinpoint because of its many possible symptoms. Better understanding each of these symptoms may provide a more targeted treatment.

I think both experiments were generally thorough and well-done, so their contrasting conclusions are that much more surprising. My guess for the discrepancy between results is due to the differences in the the stress-induction. The rodents in Tye’s experiment were likely subjected to a gentler form of stress than those in Chaudhury’s, so their positive response to the dopaminergic neuronal activation could be due to that. The rodents in Chaudhury’s experiment may have crossed a theoretical threshold of stress, turning their response to the DA activation negative and making them more susceptible to Depressive behaviors. We clearly do not fully understand why these results differ and the truly complex nature of stress and depression. More research into different types of stress and their relationship to depression may shed light on some of these answers.