Rewiring, forgetting and learning. Commentary: A critical period for experience-dependent remodeling of adult-born neuron connectivity

Citation: Martínez-Canabal A (2015) Rewiring, forgetting and learning. Commentary: A critical period for experience-dependent remodeling of adult-born neuron connectivity. Thirty years after the discovery that neurons are generated in the adult brain (Altman and Das, 1965), studies of the link between hippocampal neurogenesis and behavior revealed that exercise and environmental enrichment are highly effective at maximizing the proliferation and survival of adult-born neurons (Van Praag et al., 1999b; Bruel-Jungerman et al., 2005). Depending on the neurogenesis markers used, enriched animals exhibit a 50–200% increase in the number of new neurons compared with animals housed in standard home cages. Based on the premise that these new cells are important for cognition, several experiments show that exercise or environmental enrichment results in noticeable improvements in hippocampal-dependent task performance (Van Praag et al., 1999a; Van der Borght et al., 2007; Creer et al., 2010). Furthermore, the depletion of adult-born neurons with antimitotic drug treatment or focal radiation blocks the effect of environmental enrichment on memory (Bruel-Jungerman et al., 2005; Meshi et al., 2006). However, in nearly all of these studies, enrichment occurred before learning but not after learning. In fact, this experimental design is routinely used in the functional study of neurogenesis, not only with enrichment but also with other manipulations. However, two in vivo (Feng et al., 2001; Akers et al., 2014) and one in silico (Weisz and Argibay, 2012) experiment show that when environmental enrichment occurs after learning, previously-acquired memories are forgotten. These three studies show that as a consequence of more cells added to the hippocampal circuit, memory retention suffers. This seemingly counterintuitive result can be explained by a detailed analysis of the morphological changes driven by running and enrichment and their effect on neuronal connectivity. Specifically, newly generated axon terminals can juxtapose with or displace previously established synapses (Akers et al., 2014), thus degrading pre-existing memory circuits and resulting in forgetting. By taking advantage of the rabies virus to retrogradely infect monosynaptic neurons (Wickersham et al., 2007), a new study by Bergami et al. (2015) shows that this neurogenesis-induced rewiring occurs more extensively than previously thought. The authors created a retrovirus that tags both newly generated neurons and all neurons that have synaptic contacts with these new neurons with a TVA receptor, allowing tagged neurons to be labeled with permanently expressed GFP. They then counted the number of retroinfected cells within the dentate gyrus, the entire hippocampus, and other …