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Week 1: Neurogenesis

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Data suggests that neurogenesis continues into adulthood and is an essential process in which new neurons are derived, migrate, and inevitably integrate into circuits. It is interesting to note that although neurons and glia themselves are highly dynamic given their ability to rewire constantly, still new neurons are needed. This is especially relevant in the context of disease and disorder states, such as severe depression, in which brain atrophy is present. 
At first glance of  Santarelli et al. and Bessa et al., it is obvious that the functional relevance of neurogenesis is very hard to study. Both papers do show that neurogenesis occurs in the context of antidepressant treatment but struggle to establish a functional link between these new neurons formed and behavioral rescue of anhedonia and helplessness. This is in fact the exact rebuttal of Bessa et al. to Santarelli et al.’s claim that antidepressants work via neurogenic restoration. There is a major problem with this claim. The paper does make a good attempt at showing the necessity of neurogenesis in linking antidepressant’s improvement on NSF latency but, does not provide any functional relevance in the context of depression. For example, it would have been interesting to test the 5HT-1A receptor null mice using the CMS model in Bessa et al. or to prove that these serotonergic neurons are part of engrams responsible for overall anxiety, not just feeding behaviors. Down-regulating receptors and irradiating the hippocampus may cause brain-wide changes and labeling new mature neurons is not sufficient to prove that neurogenesis mediate antidepressants alone. 
Even though Bessa et al. contradicts the earlier link established between neurogenesis and antidepressant treatment, I think both parties would serve well to look into the role of these new neurons. In Bessa et al. it is partially concluded that these new neurons are indeed changing behavior but only robustly in NSF. But, without looking at the functional niche of these new neurons it is hard to claim that there is no link at all. As anxiety behaviors amongst individuals vary, so do their respective circuits. Possibly, these new neurons formed are associated with a specific anxiety pathway in which should be investigated further. Especially if neurogenesis is robust enough to change PFC volume, it is unfair to disregard it and claim that this is only neuronal/synaptic remodeling.
Overall, both papers do provide some convincing data in that neurogenesis is present but, it is intriguing to see how contradictory both papers really are. Many more experiments need to be done in order to truly establish a link with antidepressants, and truly understand the secondary mechanisms of action at play when these treatments are used. 

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