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RESEARCH PRODUCT

Modulating Neuronal Competition Dynamics in the Dentate Gyrus to Rejuvenate Aging Memory Circuits.

Stefan P BergerCraig RussoNannan GuoBenedikt BerningerMatteo BergamiKimberly N. ScobiePakanat DecharatanachartKathleen M. McavoyMark L. NelsonAmar SahayHugo Vega-ramirezSam Miake-lyeMichael J. WhalenDusan BartschRené Hen

subject

0301 basic medicinerac1 GTP-Binding ProteinAgingDendritic spineCell SurvivalDendritic SpinesNeurogenesisKruppel-Like Transcription FactorsRAC1BiologyNegative regulator03 medical and health sciencesMice0302 clinical medicineDownregulation and upregulationNeural Stem CellsMemorymedicineAnimalsCell ProliferationNeuronsMemory circuitsGeneral NeuroscienceDentate gyrusNeuropeptidesGranule cellUp-RegulationKLF9Adult Stem Cells030104 developmental biologymedicine.anatomical_structureDentate GyrusMutationNeuroscience030217 neurology & neurosurgery

description

The neural circuit mechanisms underlying the integration and functions of adult-born dentate granule cell (DGCs) are poorly understood. Adult-born DGCs are thought to compete with mature DGCs for inputs to integrate. Transient genetic overexpression of a negative regulator of dendritic spines, Kruppel-like factor 9 (Klf9), in mature DGCs enhanced integration of adult-born DGCs and increased NSC activation. Reversal of Klf9 overexpression in mature DGCs restored spines and activity and reset neuronal competition dynamics and NSC activation, leaving the DG modified by a functionally integrated, expanded cohort of age-matched adult-born DGCs. Spine elimination by inducible deletion of Rac1 in mature DGCs increased survival of adult-born DGCs without affecting proliferation or DGC activity. Enhanced integration of adult-born DGCs transiently reorganized adult-born DGC local afferent connectivity and promoted global remapping in the DG. Rejuvenation of the DG by enhancing integration of adult-born DGCs in adulthood, middle age, and aging enhanced memory precision.

yearjournalcountryeditionlanguage
2015-09-14Neuron
10.1016/j.neuron.2016.08.009https://pubmed.ncbi.nlm.nih.gov/27654861