Post 2: Investigation of Dopamine Neurons and Neural Firing Patterns in the VTA of Depressed Animal Models using Optogenetics

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 Naturein 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 defeat paradigms to induce stress, Tye employs a gentler chronic mild stress (CMS) paradigm As both Chaudhury and Tye acknowledge, the severity of stress modulates whether stress increases or decreases the activity of VTA dopamine neurons, with more severe stressors (like social defeat) increasing dopaminergic activity and less severe stressors (like CMS) decreasing dopaminergic activity. The severity-dependent bidirectional effects of stress on dopamine imbalance support Tye and Chaudhury’s seemingly opposing conclusions.

            While these two conclusions can logically co-exist, this is not to say that either of the papers are without limitations. I found that the poorly defined structure of both papers (presumably required by Nature) reduced the clarity and efficiency of the papers, as sections were not labeled (with Chaudhury forgoing an introduction altogether) and portions of the methods were restated throughout the results, as well as separately. Another cause for confusion: Chaudhury’s methods section details an elevated plus maze and open field test, but neither or these tests or their results are mentioned anywhere in the main paper. Despite these, and other weaknesses found in the papers, they demonstrate the utility of optogenetics in gaining an understanding of depression and, taken together, emphasize the complexity of the neurological systems that contribute to depression and other mood disorders.