Long-Lasting Plasticity of Hippocampal Adult-Born Neurons

Abstract

Adult neurogenesis occurs in the dentate gyrus of the hippocampus, which is a key structure in learning and memory. It is believed that adult-born neurons exert their unique role in information processing due to their high plasticity during immature stage that renders them malleable in response to environmental demands. Here, we demonstrate that, in rats, there is no critical time window for experience-induced dendritic plasticity of adult-born neurons as spatial learning in the water maze sculpts the dendritic arbor of adult-born neurons even when they are several months of age. By ablating neurogenesis within a specific period of time, we found that learning was disrupted when the delay between ablation and learning was extended to several months. Together, these results show that mature adult-born neurons are still plastic when they are functionally integrated into dentate network. Our results suggest a new perspective with regard to the role of neo-neurons by highlighting that even mature ones can provide an additional source of plasticity to the brain to process memory information.

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

“…Indeed, by imaging new neurons using Zif268, it has been shown that spatial learning recruited 4-mo-old adult-born neurons (Tronel et al 2014). Depleting specifically these "old" adult-born neurons (by 1-wk AraC treatment 4 mo before training) delays learning (Lemaire et al 2012). These data indicating that adult-born neurons do not have a time-dependent role are consistent with the observation that they survive several months (Kempermann et al 2003).…”

“…When testing spatial memory ability, deficits were described in some studies (Snyder et al 2005;Fan et al 2007;Dupret et al 2008;FarioliVecchioli et al 2008;Imayoshi et al 2008;Garthe et al 2009;Lemaire et al 2012), but not in others (Shors et al 2002;Madsen et al 2003;Raber et al 2004;Meshi et al 2006;Saxe et al 2006;Winocur et al 2006;Wojtowicz et al 2008). From our own study, based on a model that consisted in selectively ablating adult hippocampal neurogenesis by overexpressing the proapoptotic protein Bax in neuronal precursors on administration of doxycycline, we concluded that adult-born neurons are required for an allocentric (and not egocentric) strategy and for the flexible use of the acquired information (Dupret et al 2008).…”

“…This suggests that various signals affect the branching of the newly generated neurons. Interestingly, there is no critical time window for experience-induced dendritic plasticity of adult-born neurons as spatial learning sculpts the dendritic arbor of adult-born neurons even when they are several months old (Lemaire et al 2012). The effects of learning are specific for neurons born during adulthood as neurons born during development remained unchanged after learning (Tronel et al 2010;Lemaire et al 2012).…”

“…During this "critical period," cells are still immature, but already differentiated as neurons and express immature neuronal markers and physiological neuronal characteristics (Kempermann et al 2004;Piatti et al 2006). In contrast, learning does not influence the survival of older (2 or 4 mo) neurons that are well integrated into the network (Lemaire et al 2012). One hypothesis is that these cells have reached an adequate developmental stage to be "stabilized" by activity-dependent stimuli generated in the course of learning.…”

“…However, this does not exclude the possibility that neuromodulators may act differently on developmental and adult-born neurons. When focusing on their structural plasticity, adult-born, but not developmentally generated, neurons are able to reshape in response to learning (Tronel et al 2010;Lemaire et al 2012), suggesting that these dissimilarities confer them different functions. Some studies, indeed, highlighted a specific behavioral signature for neurons born in development ( pups or juvenile) versus adulthood (Wei et al 2011;Nakashiba et al 2012;Tronel et al 2014).…”