Changing behavior with light


        The 2013 article by Ramirez and colleagues is a phenomenal example of what can be achieved with optogenetics. The use of dox to selectively label neurons that are active at a specific time with light-dependent ChR2, so these can be activated at a later time is brilliant. Researchers were able to the activation of neurons in the dentate gyrus as a conditioned stimulus for false memory formation. While the effect of implanted memories on freezing behavior was not as strong as that of a real memory using an environmental conditioned stimulus, the effect was still very clear, leaving no margin for doubt that a false memory had been implanted. Importantly, the fact that cfos levels in the BLA and CeA of the amygdala were similar in real and false memories despite differing behavioral response indicates that the freezing response is being modulated in some other manner. Furthermore, the negative results steaming from the activation with light of CA1 neurons, despite some specificity of these neurons for context, are asking for further investigation, potentially using electric reading of the neurons, given the temporal dynamics hypothesis put forward by the authors.

          The 2015 article by the same authors build on their previous work and applies the same behavioral altering methods (which before were fear inducing) in trying to reduce negative or abnormal behaviors (i.e. anxiety and depressive behaviors). Interestingly, the authors were not able to recover the normal anxiety phenotype ins stressed animals with stimulation of positive experience engrams in the dentate gyrus, which raises questions regarding what regions might be of interest for future studies. The overall results are very impressive and have important implications for treatment and therapy of depressed patients. First, it shows that glutaminergic and dopaminergic activity is essential the recovery of the normal phenotype, which gives clues regarding the mechanism of action current medications. Finally, it demonstrates that the activation of circuits related to previous positive experiences is a viable way to recover the normal phenotype, which might be a mechanism via which the same is achieved in therapy with humans.

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