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Hippocampus. 2016 Jun;26(6):763-78. doi: 10.1002/hipo.22557. Epub 2016 Feb 8.

Activation of local inhibitory circuits in the dentate gyrus by adult-born neurons.

Drew LJ1,2, Kheirbek MA1,2,3, Luna VM1,2, Denny CA1,2, Cloidt MA2, Wu MV1,2, Jain S4, Scharfman HE4,5,6,7, Hen R1,2,3,8.

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Department of Psychiatry, Columbia University, New York, NY.
Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY.
Department of Neuroscience, Columbia University, New York, NY.
Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Bldg. 35, Orangeburg, NY.
Department of Child and Adolescent Psychiatry, New York University, Langone Medical Center, New York, NY.
Department of Physiology and Neuroscience, New York University, Langone Medical Center, New York, NY.
Department of Psychiatry, New York University, Langone Medical Center, New York, NY.
Department of Pharmacology, Columbia University, New York, NY.


Robust incorporation of new principal cells into pre-existing circuitry in the adult mammalian brain is unique to the hippocampal dentate gyrus (DG). We asked if adult-born granule cells (GCs) might act to regulate processing within the DG by modulating the substantially more abundant mature GCs. Optogenetic stimulation of a cohort of young adult-born GCs (0 to 7 weeks post-mitosis) revealed that these cells activate local GABAergic interneurons to evoke strong inhibitory input to mature GCs. Natural manipulation of neurogenesis by aging-to decrease it-and housing in an enriched environment-to increase it-strongly affected the levels of inhibition. We also demonstrated that elevating activity in adult-born GCs in awake behaving animals reduced the overall number of mature GCs activated by exploration. These data suggest that inhibitory modulation of mature GCs may be an important function of adult-born hippocampal neurons. © 2015 Wiley Periodicals, Inc.


adult neurogenesis; dentate gyrus; granule cells; hippocampus; inhibition; interneurons; optogenetics

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