Experience-Specific Functional Modification of the Dentate Gyrus through Adult Neurogenesis: A Critical Period during an Immature Stage

Abstract

Neural circuits in the dentate gyrus are continuously modified by adult neurogenesis, whose level is affected by the animal's experience. However, it is not known whether this experience-dependent anatomical modification alters the functional properties of the dentate gyrus. Here, using the expression of immediate early gene products, c-fos and Zif268, as indicators of recently activated neurons, we show that previous exposure to an enriched environment increases the total number of new neurons and the number of new neurons responding to reexposure to the same environment. The increase in the density of activated new neurons occurred specifically in response to exposure to the same environment but not to a different experience. Furthermore, we found that these experience-specific modifications are affected exclusively by previous exposure around the second week after neuronal birth but not later than 3 weeks. Thus, the animal's experience within a critical period during an immature stage of new neurons determines the survival and population response of the new neurons and may affect later neural representation of the experience in the dentate gyrus. This experience-specific functional modification through adult neurogenesis could be a mechanism by which new neurons exert a long-term influence on the function of the dentate gyrus related to learning and memory.

Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory

“…Contrasting with their putative role as comparator cells, this matched situation led, in fact, to a larger recruitment of the new neurons, indicating instead that their activity was predominantly experience-specific. Activation of new granular neurons specifically in response to exposure to the same environment, but not to a different experience, has been reported recently (6). The present results extend this finding by showing that new neurons respond preferentially to a previously encountered situation whose memory relies on the elaboration of complex cognitive maps enabling spatial navigation and storage of a specific location or goal.…”

“…At this age, new cells exhibit unique characteristics that make them particularly inclined to modification by experience (6,8,10,11). One day after spatial navigation in the water maze (i.e., 10 days after BrdU injections), we found more BrdU-labeled cells in the DG of both Spatial ϪPF and Swim animals compared with Cage control mice [F (2,15) ϭ 6.01; P Ͻ 0.05; Fig.…”

“…Supporting this idea, the increasing number of reports that have used correlative and invasive approaches indicates the existence of a functional link between hippocampal-dependent learning and adult hippocampal neurogenesis (1)(2)(3)(4)(5). Recently, it was found that new cells contribute to the functional activity patterns elicited in the hippocampus in response to performing memory tasks that solicit hippocampal networks (4,6,7).…”

Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus

“…These changes may be especially relevant for regenerative processes, for example following epileptic seizures (3), and neurogenesis induced by learning or exposure to enriched environments (see ref. 37). Although the underlying mechanisms still need to be clarified, the requirement of connexin expression for normal adult neurogenesis reported here supports the view that embryonic (see ref.…”

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

“…Exposure of mice to an enriched environment or a running wheel increases both the spatial memory ability in the water maze and the number of adult-born neurons in DG (Kempermann et al 1997(Kempermann et al , 1998aNilsson et al 1999;van Praag et al 1999a,b;Brown et al 2003;Koo et al 2003;Rossi et al 2006;Tashiro et al 2007). In addition, both neurogenesis and spatial memory performances are improved in senescent or middle-aged mice raised in an enriched environment (Kempermann et al 1998b.…”