Increase of GABAA receptor-mediated tonic inhibition in DG cells after traumatic brain injury.pdf

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Increase of GABAA receptor-mediated tonic inhibition in DG cells after traumatic brain injury.pdf

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Increase of GABAA receptor-mediated tonic inhibition in DG cells after traumatic brain injury

Neurobiology of Disease 38 (2010) 464–475 Contents lists available at ScienceDirect Neurobiology of Disease j ourna l homepage: www.e lsev ie / locate /ynbd iIncrease of GABAA receptor-mediated tonic inhibition in dentate granule cells after traumatic brain injury Zakaria Mtchedlishvili a,b,?, Eka Lepsveridze d, Hong Xu a, Elena A. Kharlamov a,b, Bo Lu a, Kevin M. Kelly a,b,c a Center for Neuroscience Research, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA b Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA c Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA d Ilia Chavchavadze State University, Faculty of Life Sciences, Tbilisi, Georgia? Corresponding author. Allegheny General Hospital, 9 Pittsburgh, PA 15212, USA. Fax: +1 412 359 6847. E-mail address: zmtchedl@ (Z. Mtchedlish Available online on ScienceDirect (www.scienced 0969-9961/$ – see front matter ? 2010 Elsevier Inc. A doi:10.1016/j.nbd.2010.03.012a b s t r a c ta r t i c l e i n f oArticle history: Received 11 November 2009 Revised 10 March 2010 Accepted 10 March 2010 Available online 18 March 2010 Keywords: Traumatic brain injury Dentate granule cells GABAA receptor Diazepam Furosemide THIP Bicuculline mIPSCs Synaptic currents Tonic currentsTraumatic brain injury (TBI) can result in altered inhibitory neurotransmission, hippocampal dysfunction, and cognitive impairments. GABAergic spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) and tonic (extrasynaptic) whole cell currents were recorded in control rat hippocampal dentate granule cells (DGCs) and at 90 days after controlled cortical impact (CCI). At 34 °C, in CCI DGCs, sIPSC frequency and amplitude were unchanged, whereas mIPSC frequency was decreased (3.10±0.84 Hz, n=16, and 2.44±0.67 Hz, n=7, pb0.05). At 23 °C, 300 nM diazepam increased peak amplitude of mIPSCs in control and CCI DGCs, but the increa