Alteration in depressive behaviors by optogenetic modulation of VTA DA neurons - John Lambert

Here are two papers that use similar methods, that mainly focus on the same disease treatment and same areas of the brain, but that seemingly found opposite results. Chaudbury et al. found that stimulating the ventral tegmental area (VTA) of mice resistant to a social-defeat paradigm induced depressive-like symptoms, while Tye et al. found that stimulating the VTA of mice exposed to chronic mild stress (CMS) instantly reversed behaviors from depressive-like to normal. The main difference between the methods used in each study, is how they induced the depressive-like behavior in the mice. Chaudbury et al. utilized a social-defeat paradigm that differed greatly from the CMS used by Tye et al. Both papers utilized nearly the same optogenetics method to selectively target VTA dopamine neurons. 
I found the papers interesting, and I agree with Tye et al. that the difference in stressors, as well as the general complexity of depression, contributed to the difference in the papers’ results. Anxiety-depression phenotypes are far from perfect, though CMS is generally agreed to be the most valid protocol for inducing depressive behavior. I am curious about any more recent research related to these papers.
While reading Tye et al. I noticed that they stimulated the VTA DA neurons using a 30 Hz frequency, which lead me to also check Chaudbury et al., they used 0.5 Hz or 20 Hz frequencies. Previous, unrelated research has demonstrated that differences in gamma oscillations (30-100 Hz) are responsible for behavioral regression in mouse models of depression, and can be used as a biomarker to identify MDD [2, 4]. The 30 Hz bursts used in the VTA of the mice in Tye et al. may have been able to boost gamma oscillations in the mice, potentially altering the outcome of the experiment. Chaudburyet al. could also have altered the normal oscillations present in the mice. While I was not able to find any research conducted that used optogenetics to induce gamma oscillations as a treatment for any disorder, it has been determined that optogenetic techniques can stimulate gamma oscillations in mice [1]. Additionally, other methods of stimulating gamma oscillations in mice are being investigated as a treatment for other neurological diseases [3].  I am in favor of further investigation into this topic, to determine how or if this influenced the findings. 

References:

1. Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., . . . Moore, C. I. (2010). Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nature Protocols, 5, 247. doi:10.1038/nprot.2009.228
2. Fitzgerald, P. J., & Watson, B. O. (2018). Gamma oscillations as a biomarker for major depression: an emerging topic. Translational Psychiatry, 8(1), 177. doi:10.1038/s41398-018-0239-y
3. Iaccarino, H. F., Singer, A. C., Martorell, A. J., Rudenko, A., Gao, F., Gillingham, T. Z., . . . Tsai, L.-H. (2016). Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature, 540, 230. doi:10.1038/nature20587
4. Khalid, A., Kim, B. S., Seo, B. A., Lee, S.-T., Jung, K.-H., Chu, K., . . . Jeon, D. (2016). Gamma oscillation in functional brain networks is involved in the spontaneous remission of depressive behavior induced by chronic restraint stress in mice. BMC neuroscience, 17, 4-4. doi:10.1186/s12868-016-0239-x

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