Week III

Ramirez et al. (2015) found that when engram cells associated with positive experiences are chronically stimulated there is an increase in neurogenesis. However, in Extended Data Figure 8 the researchers come to a slightly different conclusion, that chronic activation of positive memory cells prevents stress induced decreases in neurogenesis. These two claims imply very different implications of the clinical uses of this method. The former claim implies that optogenetic activation of positive memory cells was able to reverse the effects of stress. The latter claim implies that activation of positive memory cells simply halted the inhibition of neurogenesis in stresses animals.

The implications that optogenetic stimulation can increase neurogenesis reminded me of a paper we read a couple of weeks ago, Santarelli et al. in which researchers found that antidepressants functioned by promoting neurogenesis. Santarelli et al. suggested, “stimulation of hippocampal neurogenesis could provide novels avenues for the treatment of anxiety and depressive disorders.” Ramirez et al (2015) implied a similar idea regarding deep brain stimulation as an alternative treatment for the symptoms of depression. After reading these papers the thought occurred to me that perhaps optogenetic stimulation of hippocampal cells activated the same pathway as certain antidepressants that ultimately resulted in neurogenesis. If that is indeed the case then perhaps more research should be done focusing on the pathway that promotes/inhibits neurogenesis.

An alternative idea occurred to me as I was thinking about the connection between neurogenesis and the reversal of the depressive phenotype. The week we discussed Santarelli et al. we also discussed the Bessa et al. paper in which researchers claimed it synaptic plasticity was the mechanism by which antidepressants functioned. Perhaps the repeated activation of these positive memory cells resulted in some form of synaptic plasticity that somehow reversed the behavioral effects of stress. The result of this study that optogenetic stimulation saw an increase in neurogenesis could have provided additional insight on whether or not its neurogenesis, synaptic plasticity, or both that ultimately result in the reversal of depressive behavior. Unfortunately the researchers did not provide further comment on this finding so it is difficult to make any conclusions.