Week 2: Tye and Chaudhury

Both of these papers used optogenetics in order to assess the role of VTA dopamine neuronal function in depression-like models. I think what was most interesting in regards to these papers were the seemingly contradictory findings both had in regards to how phasic bursting of VTA dopamine neurons impacts depression-like symptoms. Tye et. al’s paper used a chronic mild stress paradigm to assess how CMS impacts bursting patterns of the VTA DA neurons and if these differential bursting patterns had any impact on depressive like symptoms. Interestingly, their findings suggest that chronic mild stress interferes with baseline bursting patterns of the VTA DA neurons – and that induced phasic bursting patterns could reduce depressive like behaviors in CMS treated mice. This was a significant finding that used experimental activation of these VTA DA neurons using optogenetic methods. Additionally, their same protocol found that induced inhibition of VTA DA neurons interferes with endogenous bursting patterns in the VTA DA system that results in an increase in depressive-like behaviors. These findings indicate that endogenous, phasic bursting of dopamine neurons in the VTA is important in maintaining a non depressive phenotype. Additionally, it suggests that interruption of these phasic bursting patterns during CMS induce a depressive-like phenotype, which can be reversed by inducing a phasic bursting pattern via optogenetics.

            The Chaudhury paper seems to contradict these findings, indicating that after a social stress paradigm an induced increase in phasic bursting patterns of dopamine neurons in the VTA causes an increase in depressive-like behaviors. Chaudhury et al. also presented findings that suggest phasic firing of VTA DA neurons is crucial in the development of depressive-like behaviors in response to stress.

            Where the two papers differ is in the stress model used. Tye used a mild stress paradigm while Chaudhury used a more acute, extreme stress paradigm. The differential findings between the two conditions show that VTA DA neurons react to different types of stress in contradictory ways. During chronic mild stress, an increase in phasic bursting of the VTA DA neurons seems to eliminate depressive-like symptoms, whereas in the severe stress paradigm used by Chaudhury, phasic bursting of the VTA DA neurons seems to exacerbate depressive like behaviors in response to stress. These differences may lie in the fact that chronic mild stress reduces DA firing while severe stress increases DA firing. This suggests that the effects of VTA DA signaling is context specific and very complex – indicating that severity of stress may differentially impact DA firing.