title: KCNQ5 K(+) channels control hippocampal synaptic inhibition and fast network oscillations.
abstract: KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) K(+) channels dampen neuronal excitability and their functional impairment may lead to epilepsy. Less is known about KCNQ5 (Kv7.5), which also displays wide expression in the brain. Here we show an unexpected role of KCNQ5 in dampening synaptic inhibition and shaping network synchronization in the hippocampus. KCNQ5 localizes to the postsynaptic site of inhibitory synapses on pyramidal cells and in interneurons. Kcnq5(dn/dn) mice lacking functional KCNQ5 channels display increased excitability of different classes of interneurons, enhanced phasic and tonic inhibition, and decreased electrical shunting of inhibitory postsynaptic currents. In vivo, loss of KCNQ5 function leads to reduced fast (gamma and ripple) hippocampal oscillations, altered gamma-rhythmic discharge of pyramidal cells and impaired spatial representations. Our work demonstrates that KCNQ5 controls excitability and function of hippocampal networks through modulation of synaptic inhibition.
authors: 1] Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Street 10, Berlin 13125, Germany [2] Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Street 10, Berlin 13125, Germany [3] Klinik für Neurologie, Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany.
authors: Pawel
authors: P
authors: Fidzinski
authors: 1] Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Street 10, Berlin 13125, Germany [2] NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany.
authors: Tatiana
authors: T
authors: Korotkova
authors: 1] Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Street 10, Berlin 13125, Germany [2] Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Street 10, Berlin 13125, Germany.
authors: Matthias
authors: M
authors: Heidenreich
authors: Neurowissenschaftliches Forschungszentrum, Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany.
authors: Nikolaus
authors: N
authors: Maier
authors: 1] Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Street 10, Berlin 13125, Germany [2] Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Street 10, Berlin 13125, Germany.
authors: Sebastian
authors: S
authors: Schuetze
authors: Leibniz-Institut für Neurobiologie (LIN), Brenneckestraße 6, Magdeburg 39118, Germany.
authors: Oliver
authors: O
authors: Kobler
authors: Leibniz-Institut für Neurobiologie (LIN), Brenneckestraße 6, Magdeburg 39118, Germany.
authors: Werner
authors: W
authors: Zuschratter
authors: 1] NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany [2] Neurowissenschaftliches Forschungszentrum, Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany [3] Deutsches Zentrum für Neurodegenerative Erkrankungen in der Helmholtz-Gemeinschaft (DZNE), Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany.
authors: Dietmar
authors: D
authors: Schmitz
authors: 1] Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Street 10, Berlin 13125, Germany [2] NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany.
authors: Alexey
authors: A
authors: Ponomarenko
authors: 1] Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Street 10, Berlin 13125, Germany [2] Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Street 10, Berlin 13125, Germany [3] NeuroCure Cluster of Excellence, Charité Universitätsmedizin, Charitéplatz 1, Berlin 10117, Germany.
authors: Thomas J
authors: TJ
authors: Jentsch
mesh_terms: D000200:Action Potentials; D000818:Animals; D059330:GABAergic Neurons / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D021381:Protein Transport; D017966:Pyramidal Cells / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D051656:KCNQ Potassium Channels; C506326:KCNQ5 channel, mouse