@article{1e867c60f30f404ebf0ce2ddd1ad2323,
title = "LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance",
abstract = "Excitatory hilar mossy cells (MCs) in the dentate gyrus receive inputs from dentate granule cells (GCs) and project back to GCs locally, contralaterally, and along the longitudinal axis of the hippocampus, thereby establishing an associative positive-feedback loop and connecting functionally diverse hippocampal areas. MCs also synapse with GABAergic interneurons that mediate feed-forward inhibition onto GCs. Surprisingly, although these circuits have been implicated in both memory formation (e.g., pattern separation) and temporal lobe epilepsy, little is known about activity-dependent plasticity of their synaptic connections. Here, we report that MC-GC synapses undergo a presynaptic, NMDA-receptor-independent form of long-term potentiation (LTP) that requires postsynaptic brain-derived neurotrophic factor (BDNF)/TrkB and presynaptic cyclic AMP (cAMP)/PKA signaling. This LTP is input specific and selectively expressed at MC-GC synapses, but not at the disynaptic inhibitory loop. By increasing the excitation/inhibition balance, MC-GC LTP enhances GC output at the associative MC-GC recurrent circuit and may contribute to dentate-dependent forms of learning and epilepsy.",
keywords = "BDNF, CA3, TrkB, hippocampus, learning, memory, pattern separation, presynaptic",
author = "Yuki Hashimotodani and Kaoutsar Nasrallah and Jensen, {Kyle R.} and Ch{\'a}vez, {Andr{\'e}s E.} and Daniel Carrera and Castillo, {Pablo E.}",
note = "Funding Information: We thank Dr. Yoav Ben-Simon (Tel Aviv University) for providing AAV-hSyn-ChIEF-citrine, Dr. Lisa Monteggia (University of Texas, Southwestern Medical Center) for providing TrkB-floxed mice, and Hannah Monday for critical review of the manuscript and assistance with confocal imaging. We also thank Stefano Lutzu and Pablo Lituma for their help with the two-photon laser microscope. This work was supported by NIH R01 grants DA017392 and MH081935 to P.E.C. Y.H. was supported by the Japan Society for the Promotion of Science postdoctoral fellowships for research abroad (H23.829). K.N. was supported by the Fondation pour la Recherche M{\'e}dicale (postdoctoral fellowship for research abroad) and the Fondation Bettencourt Schueller (Prix pour les jeunes chercheurs 2016). A.E.C. was partially supported by a Ruth L. Kirschstein Award (F32 NS071821), a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation, and by the Millennium Nucleus Nu-MIND (NC 130011). D.C. was supported by the Maximizing Access to Research Careers Program (T34 GM008718) and the Albert Einstein College of Medicine Summer Undergraduate Research Program (R25 GM104547). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = aug,
day = "16",
doi = "10.1016/j.neuron.2017.07.028",
language = "English (US)",
volume = "95",
pages = "928--943.e3",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",
}