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eNeuro. 2018 Dec 3;5(6). pii: ENEURO.0137-18.2018. doi: 10.1523/ENEURO.0137-18.2018. eCollection 2018 Nov-Dec.

Development of GABAergic Inputs Is Not Altered in Early Maturation of Adult Born Dentate Granule Neurons in Fragile X Mice.

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Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208.


Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most common known cause of autism. Loss of fragile X mental retardation protein (FMRP) in mice (Fmr1 KO) leads to altered synaptic and circuit maturation in the hippocampus that is correlated with alterations in hippocampal-dependent behaviors. Previous studies have demonstrated that loss of FMRP increased the rate of proliferation of progenitor cells and altered their fate specification in adult Fmr1 KO mice. While these studies clearly demonstrate a role for FMRP in adult neurogenesis in the hippocampus, it is not known whether the functional synaptic maturation and integration of adult-born dentate granule cells (abDGCs) into hippocampal circuits is affected in Fmr1 KO mice. Here, we used retroviral labeling to birthdate abDGCs in Fmr1 KO mice which allowed us to perform targeted patch clamp recording to measure the development of synaptic inputs to these neurons at precise time points after differentiation. The frequency and amplitude of spontaneous GABAergic events increased over the first three weeks after differentiation; however, this normal development of GABAergic synapses was not altered in Fmr1 KO mice. Furthermore, the relatively depolarized GABA reversal potential (E GABA) in immature abDGCs was unaffected by loss of FMRP as was the development of dendritic arbor of the adult generated neurons. These studies systematically characterized the functional development of abDGCs during the first four weeks after differentiation and demonstrate that the maturation of GABAergic synaptic inputs to these neurons is not grossly affected by the loss of FMRP.


GABA; adult born neurons; fragile X; neurogenesis; synapse

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