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Adult-born hippocampal neurons bidirectionally modulate entorhinal inputs into the dentate gyrus

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Science  10 May 2019:
Vol. 364, Issue 6440, pp. 578-583
DOI: 10.1126/science.aat8789

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Afferents modulate newborn neurons

What is the role of adult neurogenesis in learning, memory, and mood? Luna et al. found that adult-born neurons either inhibited or excited the dentate gyrus, depending on whether synaptic inputs originated from the lateral or the medial entorhinal cortex (see the Perspective by Llorens-Martín). These opposing mechanisms were driven by extrasynaptic transmission from adult-born neurons directly onto mature granule cells via metabotropic glutamate receptors or N-methyl-D-aspartate receptors, respectively. The balance between these mechanisms could explain the differences in dentate gyrus activity during two versions of an active place-avoidance task. The action of adult-born neurons thus depended entirely on the demands of the environment, which can be defined by the activity of cortical and subcortical regions sending inputs to the dentate gyrus.

Science, this issue p. 578; see also p. 530

Abstract

Young adult-born granule cells (abGCs) in the dentate gyrus (DG) have a profound impact on cognition and mood. However, it remains unclear how abGCs distinctively contribute to local DG information processing. We found that the actions of abGCs in the DG depend on the origin of incoming afferents. In response to lateral entorhinal cortex (LEC) inputs, abGCs exert monosynaptic inhibition of mature granule cells (mGCs) through group II metabotropic glutamate receptors. By contrast, in response to medial entorhinal cortex (MEC) inputs, abGCs directly excite mGCs through N-methyl-d-aspartate receptors. Thus, a critical function of abGCs may be to regulate the relative synaptic strengths of LEC-driven contextual information versus MEC-driven spatial information to shape distinct neural representations in the DG.

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