Week 2

After reading both of these papers, I think it is really interesting that the type of stress used to induce a depressive model has such a large effect on the circuitry involved. Tye et al used a chronic mild stress (CMS) and found that phasic activation of VTA dopamine neurons helps relieve depressive behaviors. On the other hand, Chaudhury et al used a social-defeat stress paradigm (severe stress) and found that phasic activation of the VTA dopamine neurons caused an increase in depressive behaviors. Both papers used similar behavioral outcomes, anhedonia and sucrose preference, making them easy to compare. However, both papers were published on the same date, so neither of them addressed the results found in the other paper.

      Tye et al had a small investigation into how CMS may affect VTA neuronal activity, which might be the link to why CMS can produce a different outcome from using severe stress. Tye et al states that non-stressed rats had VTA neuronal activity with a “greater proportion of spikes occurring within bursts, had longer-duration bursts, and had more spikes in each burst compare to VTA neurons in CMS rats”. I don’t know much about neuronal firing patterns, but from the information given in Chaudhury et al, it sounds like the changes described in Tye et al might be an increase of phasic firing in the VTA neurons in non-stressed rats. If this is true, then it makes sense that, if chronic mild stress reduces the phasic firing of VTA neurons, that increasing the phasic firing of those neurons could reverse depressive behaviors. This would mean that causing severe stress has to create a different neuronal activity change in the VTA, possibly by increasing the phasic firing to a dangerous level which can then be ameliorated by inhibiting phasic VTA activation. I would be interested to see the changes in neuronal activity in animals with the social-stress defeat paradigm used in Chaudhury et al.

Both of these papers speak to the importance of learning more about the etiology and pathology of mental diseases. Currently, the umbrella terms like depression may be encompassing multiple diseases with different causes and circuitry changes involved, that simply manifest with similar symptoms. If we can better understand the circuitry involved, then it will be easier to find treatments that will work for specific patients.