Two sides of the same coin?: the bidirectional effects of VTA-NAc DA neurons - Emily Jones
Papers like the ones assigned this week reminded of the reasons I opted to take this class. Research into the biological nuances of complex clinical disorders really reinforces the idea that everything psychological is simultaneously biological. And in these papers, optogenetics amazingly gives us a fast and efficient way to explore these nuances.
Interestingly, both papers demonstrated a bidirectional effect of dopamine neurons in the VTA-NAc pathway on depression phenotypes using phasic photoactivation. However, it seemed that these effects were flipped. In other words, when Chaudhury et al. inhibited the neurons, a resilient phenotype was induced in previously susceptible mice (indicated by a high preference for sugar water and decreased social avoidance compared to control mice); when Tye et. al. use the same opsin to inhibit the same kind of neurons, depression phenotypes were induced. Indeed the differences may be due in large part to the different stress conditions the mice were subjected to before treatment. In the paper by Tye and colleagues, it was found that in mice who have undergone 8-12 weeks of chronic mild stress and received the ChR2 injection returned to non-CMS levels of depression-like behavior once their neurons were stimulated phasically blue light. At the same time, Chaudhury and colleagues also studied the role of midbrain dopamine neurons in the regulation of depression-related behaviors. However, this team observed the opposite effects. In mice who were subject to subthreshold social defeat and were injected with ChR2, turning on phasic stimulation (in contrast to tonic stimulation) induced a “robust increase in the depression-like phenotypes.” These findings speak volumes to the fact that different kinds of depression stressors manifest in different ways biologically and merits studies on all kinds of stress models.
All in all, I think the two papers give invaluable insight into the different ways that external stress can impact the brain. Taking the two papers into account, I wonder if there are mice who are more or less susceptible to chronic mild stress, similar to how some mice were susceptible to social defeat stress in Chaudhury and colleagues’ study. If so, would a conceptual replication of Tye and colleagues’ study separating the resilient and susceptible mice still yield the same results?
It is clear that depression involves intermingled and complex neurological processes. While research may seem like endless chipping away to the answer, techniques like optogenetics can help us untangle the web; pathway by pathway, circuit by circuit.
Interestingly, both papers demonstrated a bidirectional effect of dopamine neurons in the VTA-NAc pathway on depression phenotypes using phasic photoactivation. However, it seemed that these effects were flipped. In other words, when Chaudhury et al. inhibited the neurons, a resilient phenotype was induced in previously susceptible mice (indicated by a high preference for sugar water and decreased social avoidance compared to control mice); when Tye et. al. use the same opsin to inhibit the same kind of neurons, depression phenotypes were induced. Indeed the differences may be due in large part to the different stress conditions the mice were subjected to before treatment. In the paper by Tye and colleagues, it was found that in mice who have undergone 8-12 weeks of chronic mild stress and received the ChR2 injection returned to non-CMS levels of depression-like behavior once their neurons were stimulated phasically blue light. At the same time, Chaudhury and colleagues also studied the role of midbrain dopamine neurons in the regulation of depression-related behaviors. However, this team observed the opposite effects. In mice who were subject to subthreshold social defeat and were injected with ChR2, turning on phasic stimulation (in contrast to tonic stimulation) induced a “robust increase in the depression-like phenotypes.” These findings speak volumes to the fact that different kinds of depression stressors manifest in different ways biologically and merits studies on all kinds of stress models.
All in all, I think the two papers give invaluable insight into the different ways that external stress can impact the brain. Taking the two papers into account, I wonder if there are mice who are more or less susceptible to chronic mild stress, similar to how some mice were susceptible to social defeat stress in Chaudhury and colleagues’ study. If so, would a conceptual replication of Tye and colleagues’ study separating the resilient and susceptible mice still yield the same results?
It is clear that depression involves intermingled and complex neurological processes. While research may seem like endless chipping away to the answer, techniques like optogenetics can help us untangle the web; pathway by pathway, circuit by circuit.
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