Sunday, September 25, 2016

9/26 Tye/Chaudhury

Both papers pointed out that tests measuring depression-like symptoms aren’t always helpful in studying depression. The Chaudhury paper said that chronic mild stress (CMS) paradigms and physically aversive stimuli inhibit ventral tegmental area (VTA) dopamine neurons, whereas more severe stressors and severe social stressors will increase neuron activity. Because of this, both papers agree that a different method must be used to study depression-like behaviors.

Instead, they suggest studying circuits that are translational between rodents and humans. Both papers researched the VTA-NAc pathway by stimulating dopamine neurons using optogenetics. This has shown to be an important pathway in depression, especially relating to susceptibility vs. resilience. However, they differed by the stressor used to cause the depression-like behaviors.

Tye et al. temporally excited VTA dopamine neurons using channelrhodopsin-2 (ChR2) in a phasic firing pattern. When combined with a twelve-week CMS paradigm, illumination increased kicking and swimming behavior in ChR2 animals. They found that locomotion wasn’t increased in an open field test (OFT), so the increase in movement was from VTA dopamine activation, not just a general increase in locomotion.

Chaudhury et al. investigated the use of optogenetics in resilient vs. susceptible animals that were subjected to a ten-day social defeat stress paradigm. They used ChR2 to phasically induce VTA dopamine neuron firing. Optical phasic firing stimulation of the VTA-NAc dopamine neuronal pathway induced the depression-like phenotype in socially stressed mice. By inhibiting the VTA-NAc pathway by using a halorhodopsin (NpHR), the mice subjected to social stress became more resilient. They discovered that susceptible mice have increased dopamine neuron firing in this circuit.

The results of the two papers suggests that further research should be done on brain circuits to treat depression, and optogenetics seems like a valuable way to approach it.

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