From pattern separation to mood regulation: multiple roles for developmental signals in the adult dentate gyrus

نویسندگان

  • Marlena Wosiski-Kuhn
  • Alexis M. Stranahan
چکیده

OVERVIEW OF ADULT HIPPOCAMPAL NEUROGENESIS The dentate gyrus represents a unique system for the study of interactions between neuronal development and experience. While this hippocampal subfield has been extensively investigated in relationship to the ongoing process of adult neurogenesis, the mnemonic contributions of mature granule neurons have remained enigmatic. Much of the rationale for focusing on newly generated neurons, as opposed to mature granule cells, rests on the greater excitability of immature neurons, which positions them to make a unique contribution to memory processing. On the other hand, the assertion that mature granule cells are either inactive, or very finely tuned to specific spatial configurations, is derived from electrophysiological recording experiments and measures of immediate early gene expression conducted under conditions that are not likely to evoke significant psychological or physiological stress. In this Opinion piece, we present the argument that mature dentate granule neurons are synaptically silent under low-stress conditions, but are recruited in far greater numbers under emotionally salient conditions due to their combined input from the amygdala and entorhinal cortex. Functional activation of the far more numerous mature granule cell population could potentially serve as an emotional tag linking spatial context with stressful experiences. The underlying mechanism for emotional tagging of spatial contexts likely involves signaling cascades implicated in neuronal development, such as the reelin signaling pathway. Alterations in reelin signaling among mature granule neurons could therefore determine their ability to disambiguate stressful and nonstressful contexts. Adult born neurons account for up to 10% of the entire granule cell population (Imayoshi et al., 2008), and at the point of senescence, nearly forty percent of granule neurons will have been born in adulthood (Snyder and Cameron, 2012). The functional significance of dentate neurogenesis is thought to arise from the distinct synaptic properties of newly generated neurons, with the assumption that increased excitability among new neurons favors their recruitment over the mature dentate granule neuron population. A number of studies have hypothesized mature granule neurons may in fact be functionally silent (Aimone et al., 2010; Alme et al., 2010), but an alternative interpretation can be generated by comparing across studies that evaluated the recruitment and functional significance of dentate gyrus granule cells under lowor high-stress conditions. Although the distributed innervation of dentate granule neurons favors sparse coding, with approximately three percent of granule cells exhibiting firing during exploration of an environment (Chawla et al., 2005; Leutgeb et al., 2007; Treves et al., 2008), these recordings were conducted under low-stress conditions that may not recruit as many mature dentate granule cells. Sparse activation of functionally mature dentate granule cells is sufficient for recall of contextual fear memory (Liu et al., 2012), suggesting that although the proportion of mature granule cells recruited by an experience may be relatively small, the selective recruitment of specific ensembles is involved in the behavioral expression of memory for stressful contexts. Given that the dentate gyrus receives extensive innervation from the amygdala (Wheal and Miller, 1980; Bergado et al., 2007)), mature granule cells may be functionally poised for activation only under conditions of high emotional salience.

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2013