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Post 2 Reward Circuitry and Depression

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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 relative activation or deactivation of these regions. But, the story is not the same for both studies. First, Tye et al. shows that VTA inhibition causes depressive phenotypes after chronic mild stress as decreased sucrose preference and learned helplessness is seen. On the other hand, Chaudhury et al. demonstrates that similar inhibition in response to social defeat stress causes a rescue of depressive phenotypes of social avoidance and lack of sucrose preference. In fact, these phenotypes are seen when the animal undergoes phasic activation. 
It is possible to speculate that these opposite effects of optogenetic control are seen either by using different targeting strategies or due to differences in behavioral and stress paradigms. It is possible that the different viruses (AAV vs. HSV) and targeting strategies (straight injection vs. cre) may be targeting select groups of neurons that are recruited differently to produce various tonic output to the NAc. Also, just as how different stressors in humans may both cause depression but with different symptomatology, social avoidance may not produce as much of a reward driven phenotype as the tail suspension test or vice versa. 
Overall, it is very intriguing to see such opposite results in papers published so close together in the same journal. In comparing these papers, it seems that there is another alternate mechanism at play that can modulate the bidirectional nature of the VTA-NAc pathway when implicated in these depressive phenotypes.

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