Week 2 Optogenetics

Optogenetics involves the control of specific neuronal populations through light waves and is a novel technology that can be used to directly study certain neurotransmitter pathways. The model of depression has long been studying the effects of dopamine on depression and depressive behaviors. The role of this circuit was looked at in the two papers discussing phasic and tonic firing of VTA dopamine neurons as a contributor in elevating depressive symptoms or causing susceptibility towards them.

            In the first paper, Tye et al find that through the CMS model of depressive behaviors that a phasic firing of VTA dopamine neurons alleviates the depressive symptoms quickly and that this effect also requires functioning DA receptors in the NAc. Their alternative finding was that inhibiting these same neurons induced a depressive behavior state. These results would lead one to believe that the firing of DA neurons in the VTA plays an important role in depression. I appreciated that Tye et al included a locomotion control test in order to assess whether CMS or induced inhibition of VTA DA neurons reduced general locomotion. This control showed that these systems were not being affected through their experimental manipulations of DA signaling and thus stood to strengthen the findings that CMS and induced inhibition of VTA DA neurons caused a reduction of struggle behavior associated with a tail suspension test.  Even with these measures, Tye et al admit to the fact that their findings should be looked at as a beginning for understanding how the DA circuit mediates these effects. This is because depression is a complex illness and that it is not fully clear what downstream target the VTA has that is changing the depression related behaviors.

            Chaundry et al had very different findings regarding the stimulation of DA neurons in the VTA. They found through their social-defeat stress model of depression that phasic firing of the DA neurons in the VTA actually lead to depressive related behaviors being induced. This finding was backed up by looking at the VTA projections to the NAc and the mPFC in order to see if the depressive susceptibility needed either brain area to mediate its effects. It was seen to be true that the phasic activation of the NAc from DA neuron projections was the area that mediated such effects.

            Since both papers looked at the phasic firing of the DA neurons in the VTA but found almost opposite effects then the differences must come down to the stress paradigms in which each experiment was run. The CMS model is seen as causing low levels of stress in comparison to the higher stress of the social-defeat model. Both methods affect the brains normal bursting activity and it is through this alteration that both groups of researchers believe depressive behaviors are being mediated.  The CMS low stress model showed that phasic firing of the VTA relieved depressive related behaviors while the social-defeat high stress model showed that the phasic firing of the VTA caused depressive related behaviors. It is possible (and likely) that both are true and that the levels of stress play a role in the determination of depressive related behaviors and that firing patterns in the VTA will cause their seen effects based on this stressor. Knowing of both pieces of research can lead to another study that looks at the effects of differing stress paradigms and phasic firing of the VTA on depression.