Adult‐born neurons are necessary for extended contextual discrimination

Abstract

New neurons are continuously produced in the adult dentate gyrus of the hippocampus. It has been shown that one of the functions of adult neurogenesis is to support spatial pattern separation, a process that transforms similar memories into nonoverlapping representations. This prompted us to investigate whether adult-born neurons are required for discriminating two contexts, i.e., for identifying a familiar environment and detect any changes introduced in it. We show that depleting adult-born neurons impairs the animal's ability to disambiguate two contexts after extensive training. These data suggest that the continuous production of new dentate neurons plays a crucial role in extracting and separating efficiently contextual representation in order to discriminate features within events.

Conditional reduction of adult neurogenesis impairs bidirectional hippocampal synaptic plasticity

“…This approach has several advantages, because it is not associated with any of the side effects that accompany the use of irradiation or the administration of pharmacologic compounds (17,18). Moreover, it targets specifically hippocampal neurogenesis without affecting olfactory neurogenesis (6,12,13). More importantly, such a partial ablation of adult-born neurons is reversible, enabling validation of a direct role of adult neurogenesis in governing synaptic strength in the DG.…”

“…Adult male transgenic mice were obtained from the breeding of Tet-Bax with Nestin-rtTA founder mice, as described previously (6,12,13). In brief, in this model, Dox administration to bigenic mice activates the nestin-controlled transactivator (rtTA), which drives the transcription of the proapoptotic Bax gene in the adult brain and not in peripheral tissues.…”

“…To address these issues, we took advantage of an inducible transgenic mouse that allows the reduction of adult hippocampal neurogenesis (6,12,13). In this model, neural precursors (expressing nestin) can be selectively killed in double-transgenic mice (bigenic mice) through overexpression of the proapoptotic protein Bax after the oral administration of an exogenous tetracycline analog, doxycycline (Dox; SI Materials and Methods).…”

“…In this model, neural precursors (expressing nestin) can be selectively killed in double-transgenic mice (bigenic mice) through overexpression of the proapoptotic protein Bax after the oral administration of an exogenous tetracycline analog, doxycycline (Dox; SI Materials and Methods). We have previously shown that disruption of adult neurogenesis strongly affects the processing of spatial and emotional information (6,12,13).…”

Interaction between Neurogenesis and Hippocampal Memory System: New Vistas

“…At the behavioral level, the data obtained so far suggest that immature neurons are not involved in this process (Deng et al 2013). Deficits appear when training occurs 2 mo (and not earlier) after depleting or increasing adult neurogenesis, suggesting that mature adult-born neurons are involved in PS (Clelland et al 2009;Sahay et al 2011;Nakashiba et al 2012;Tronel et al 2012;Groves et al 2013). …”