Looking into the complexity of the role dopamine neurons play in depression

The combination of the two papers, Chaudhury et al and Tye et al, show the complexity of dopaminergic neurons and their role in depression. They both identify different roles that phasic firing of dopaminergic neurons have in affecting depression, but I still feel that the water is very muddy. The two papers are consistent with fact that the effects of dopaminergic neurons hinge on the phasic firing of the neurons. After that distinction, the papers present many different complex pathways that involve phasic firing. Chaudhury goes on to show that depressive symptoms are not solely firing frequency based, but also heavily context based. Firgure 3-b shows that the VTA-NAc neuron has a significant increase in firing rate among susceptible mice, whereas Figure 4-b shows that the VTA-mPFC neuron shows a significant decrease in firing rate among susceptible mice. Depending on the circuit and the pathway, firing rate is adjusted. This difference hints at the complexity of the dopamine connections, but I still think that there is a lot that needs to be done in terms of understanding the circuitry.

 Tye et al adds to the complexity of the dopaminergic neuron role in the experiments showing how both inhibiting and exciting dopamine neurons play a role. By using neurons containing eNpHR, upon activation by light the dopamine neurons were inhibited though hyperpolarization. These mice showed significant decreases in both the time spend struggling and sucrose preference. To show the other side of the spectrum, they activated dopamine neurons of mice that were subjected to chronic mild stress and were able to significantly increase the time that these mice spent struggling and increase their preference for sucrose. This part of the experiment is especially interesting because it kind of mimics the way that an antidepressant might alleviate the depression of a previously stressed individual. Tye went on to show how VTA dopamine neurons can stimulate the encoding of escape based behavior.

These papers helped bring to light different ways that dopamine neurons work, but they only open the door to the complexity of the circuits. These papers provide the knowledge for more focused experiments on specific circuits in the future.