Abnormalities in GABAergic synaptic transmission of intralaminar thalamic neurons in a genetic rat model of absence epilepsy |
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| Authors: | Brockhaus Johannes Pape Hans-Christian |
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| Institution: | 1. Department of Physiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada;2. Michael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC V6T 1Z4, Canada;1. Department of General Surgery, Chengdu Second People''s Hospital, No.10, Qingyun South Street, Jinjiang District, 610017 Chengdu, Sichuan Province, People''s Republic of China;2. Department of Hepatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People''s Republic of China;1. Department of Neurology, College of Medicine, Korea University, Seoul, Republic of Korea;2. Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea;3. Department of Neurology, College of Medicine, Konkuk University, Seoul, Republic of Korea;1. Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada;2. Human Biology Program, University of Toronto, Toronto, ON M5S 1A8, Canada;3. Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON M5S 1A8, Canada;1. Neuroscience Center, General Hospital of Ningxia Medical University, Key Laboratory for Craniocerebral Diseases of Ningxia Hui Autonomous Region, Yinchuan, China;2. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, USA;3. Department of Human Anatomy, Histology and Embryology, Ningxia Medical University, Yinchuan, China;4. Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan, China;1. Department of Child and Adolescent Psychiatry, Ann and Robert H. Lurie Children''s Hospital of Chicago, Chicago, IL, United States;2. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States;3. Florey Institute of Neuroscience and Mental Health, Melbourne, Australia;4. New York University School of Medicine, New York, NY, United States;5. Department of Public Health, Northern Illinois University, DeKalb, IL, United States;6. Department of Medicine, University of Melbourne, Parkville, Victoria, Australia;7. Epilepsy Center, Ann and Robert H. Lurie Children''s Hospital of Chicago, Chicago, IL, United States;8. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, United States |
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| Abstract: | Synaptic activity mediated via GABA receptors in thalamic circuits is critically involved in the generation of hypersynchrony associated with absence epilepsy. Neurons of "unspecific" intralaminar thalamic nuclei display characteristic burst patterns during seizure activity, although their synaptic properties remain largely unknown. Here, we used in vitro patch-clamp techniques in neurons of the paracentral (PC) thalamic nucleus, derived from a genetic model of absence epilepsy (WAG-Rij) and a non-epileptic control strain (ACI) to elucidate intrinsic and synaptic properties. PC neurons displayed voltage-dependent low threshold spike bursts or tonic spike firing, typical of thalamic neurons. These parameters, and electrotonic properties, were similar in PC neurons of the two strains. Analyses of miniature inhibitory post synaptic currents (mIPSCs) mediated via GABA(A) receptors revealed no difference in decay time constant and inter-event interval between strains, but a significantly larger amplitude and higher single channel conductance (as assessed by non-stationary variance analysis) in WAG-Rij compared to ACI. By comparison, thalamocortical neurons from the ventrobasal complex of the thalamus showed no difference in mIPSC kinetics and unitary conductance between the two rat strains. In view of the critical role of GABAergic inhibition for synchronous activity in thalamocortical circuits, it is concluded that the increase in unitary conductance of IPSCs in PC neurons contributes to hypersynchrony characterizing seizure activity. |
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