Influence of ontogenetic age on the role of dentate granule neurons

Abstract

New neurons are continuously produced in the adult dentate gyrus of the hippocampus, a key structure in learning and memory. It has been shown that adult neurogenesis is crucial for normal memory processing. However, it is not known whether neurons born during the developmental period and during adulthood support the same functions. Here, we demonstrate that neurons born in neonates (first postnatal week) are activated in different memory processes when they are mature compared to neurons born in adults. By imaging the activation of these two different neuron generations in the same rat and using the IEG Zif268 and Fos, we show that these neurons are involved in discriminating dissimilar contexts and spatial problem solving, respectively. These findings demonstrate that the ontogenetic stage during which neurons are generated is crucial for their function within the memory network.

Early survival and delayed death of developmentally‐born dentate gyrus neurons

“…Whether it is in fact desirable to rescue developmentally-born neurons is another question, as they appear to be fundamentally different from (even relatively old) adult-born neurons. Adult-born neurons have greater experience-dependent morphological plasticity (Lemaire et al, 2012;Tronel et al, 2010), display unique experience-dependent patterns of IEG expression (Snyder, Radik, Wojtowicz, & Cameron, 2009;Snyder et al, 2011;Tronel et al, 2014), and have distinct functions in contextual encoding (Danielson et al, 2016;Nakashiba et al, 2012). Thus, culling developmentally-born neurons and replacing them with new neurons may in fact be beneficial, particularly if the developmentally-born neurons are less plastic and have formed maladaptive associations.…”

“…Electrophysiological properties may ultimately be similar once cells have reached maturity (Laplagne et al, 2006). However, different IEG responses to experience (Tronel, Lemaire, Charrier, Montaron, & Abrous, 2014) and enhanced morphological plasticity in old adult-born cells (Tronel et al, 2010) suggest that there may be persistent differences between DG neurons born at different ages. Understanding the behavioral contribution of developmentally-born neurons also depends on their patterns of survival.…”

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

“…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). However, others reported a functional equivalence between these different neuronal populations (Stone et al 2011b).…”

“…Finally, in contrast to what was proposed in the early retire-ment hypothesis, mature adult-born neurons are permanently functionally integrated into neuronal network. 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).…”

Daily access to sucrose impairs aspects of spatial memory tasks reliant on pattern separation and neural proliferation in rats

“…However, more loosely, "behavioral pattern separation" refers to processes that enhance discrimination among similar stimuli (Kent et al 2016). The dentate gyrus (DG) is a site of adult hippocampal neurogenesis (Kuhn et al 1996;Cameron and McKay 2001) and is hypothesized to be a neural substrate for behavioral pattern separation processes (Sahay et al 2011;Tronel et al 2015). Reductions in adult hippocampal neurogenesis by X-ray irradiation impaired performance when an array of visual target touchscreen stimuli were presented with little spatial separation, but not when the stimuli were more widely separated in space, indicating that neurogenesis is required to discriminate between similar spatial locations (Clelland et al 2009).…”