Biopsych seminar 2020

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 d...

Chaudhury et al. and Tye et al. present two opposing viewpoints in regards to the mechanisms behind depression and depressive-like behavior. I was surprised to find that both these papers were published in the same issue of Nature in 2012. Whereas Chaudhury et al. establishes two links—one between the excitation of VTA dopaminergic neuron phasic firing patterns and a susceptibility to a depression-like phenotype as well as one between the inhibition of the same VTA neuronal projections to the nucleus accumbens (validated by a social defeat behavioral paradigm and sucrose preference test)—Tye et al. utilizes a tail-suspension test as a CMS paradigm as well as a sucrose preference test to claim that a reduced modulation of dopamine cell firing in the VTA causes depressive-like symptoms whereas the inhibition of VTA dopaminergic projection neurons to the nucleus accumbens increases depressive phenotypes. I would assert that both arguments are backed with adequate resear...

The two articles, Tye et al. (2012) and Chaudhury et al. (2012), both investigated how manipulating dopamine neurons using optogenetics impacts depression-related behavior, but they came to contradicting conclusions. While Chaudhury’s study discovered that increasing phasic signaling from the ventral tegmental area (VTA) increased depression-related behavior, Tye et al. found that inducing phasic signaling in the same pathway resulted in an decrease in depression-related behavior. Based on the evidence presented in the two studies, it is difficult to decide which I am more inclined to believe as I feel like both articles had flaws. In my opinion, Chaudhury was more thorough in its methods. By breaking VTA signaling into specific projection routes, VTA to NAcc and VTA to medial prefrontal cortex (mPFC), this lead to a more comprehensive approach to the understanding the susceptibility of mice to depressive-related behavior. I would have like to have seen Tye et al. do t...

Symptoms of depression, amongst many others, include anhedonia, anxiety, and helplessness, all of which may be modulated by motivation and reward salience. Both papers, Tye et al. 2012 and Chaudhury et al. 2012 aim to understand how dopaminergic signaling links reward circuitry to these behavioral phenotypes specifically in the contexts of stressors related to depression. It is well understood that the ventral tegmental area (VTA)  acts as a reward processor via dopaminergic signalling. The VTA signals to the nucleus accumbens (NAc) in which acts as the gatekeeper for reward-based behavioral output. Both papers harness the temporal and circuit-specific power of optogenetic manipulation in order to test the sufficiency and necessity of the VTA-NAc circuit in modulating depressive behaviors and susceptibility to stress. Interestingly enough, a bidirectional nature of the VTA and the VTA-NAc pathway is seen in that either depressive states are apparent or not at all based on the rel...

Chaudhury et al. and Tye et al. both published articles about the use of optogenetics to investigate the effects of dopamine neurons and their firing patters in the VTA on depressive behaviors in  Nature in 2012. While their experiments had numerous similarities in purpose and methods, the details of their procedures revealed seemingly contrasting results that highlight the complexity of the neurological manifestation and treatment of depression. While Tye primarily concludes that dopamine activation, particularly in a phasic neural pattern, reverses the depressive-like behaviors exhibited by stress-induced mice, Chaudhury concludes that phasic firing of VTA dopamine neurons in stress-induced mice is suggestive of susceptibility for depressive behaviors.             One difference between the two experiments that may contribute to their contradictory results is the stress paradigm used. While Chaudhury uses social defe...

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...