title: Thalamocortical-auditory network alterations following cuprizone-induced demyelination.
abstract: Demyelination and remyelination are common pathological processes in many neurological disorders, including multiple sclerosis (MS). Clinical evidence suggests extensive involvement of the thalamocortical (TC) system in patients suffering from MS.
  
  
  
  Using murine brain slices of the primary auditory cortex, we investigated the functional consequences of cuprizone-induced de- and remyelination on neuronal activity and auditory TC synaptic transmission in vitro.
  
  
  
  Our results revealed an impact of myelin loss and restoration on intrinsic cellular firing patterns, synaptic transmission, and neuronal plasticity in layer 3 and 4 neurons of the auditory TC network. While there was a complex hyper- and depolarizing shift of the resting membrane potential, spontaneous and induced action potential firing was reduced during demyelination and early remyelination. In addition, excitatory postsynaptic potential amplitudes were decreased and induction of LTP was reduced during demyelination.
  
  
  
  These data indicate that demyelination-induced impairment of neurons and network activity within the TC system may underlie clinical symptoms observed in demyelinating diseases, corroborating human findings that disease progression is significantly correlated with microstructural tissue damage of the TC system. Further investigation into focal inflammation-induced demyelination models ex vivo and in vivo are needed to understand the functional implication of local and remote lesion formation on TC network activity in MS.
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, University of Münster, Robert-Koch-Straße 27a, 48149, Münster, Germany.
authors.forename: Nikoo
authors.initials: N
authors.lastname: Ghaffarian
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, University of Münster, Robert-Koch-Straße 27a, 48149, Münster, Germany.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mesgari
authors.affiliation: Department of Neurology, Westfälische Wilhelms-Universität, University of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Cerina
authors.affiliation: Department of Neurology, Westfälische Wilhelms-Universität, University of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Göbel
authors.affiliation: Institute of Physiology I, Westfälische Wilhelms-Universität, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Budde
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, University of Münster, Robert-Koch-Straße 27a, 48149, Münster, Germany.
authors.forename: Erwin-Josef
authors.initials: EJ
authors.lastname: Speckmann
authors.affiliation: Department of Neurology, Westfälische Wilhelms-Universität, University of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. sven.meuth@ukmuenster.de.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, University of Münster, Robert-Koch-Straße 27a, 48149, Münster, Germany. gorjial@uni-muenster.de.|Department of Neurology, Westfälische Wilhelms-Universität, University of Münster, Albert-Schweitzer-Campus 1, Building A1, 48149, Münster, Germany. gorjial@uni-muenster.de.|Department of Neurosurgery, Westfälische Wilhelms-Universität Münster, Münster, Germany. gorjial@uni-muenster.de.|Shefa Neuroscience Research Center, Khatam-Alanbia Hospital, Tehran, Iran. gorjial@uni-muenster.de.
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001303:Auditory Cortex / Q000473:pathology*; D001306:Auditory Pathways / Q000187:drug effects* / Q000503:physiopathology; D001703:Biophysics; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D018991:Myelin Proteolipid Protein; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018408:Patch-Clamp Techniques; D055366:Synaptic Potentials / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
chemical_list: D008996:Monoamine Oxidase Inhibitors; D018991:Myelin Proteolipid Protein; D003471:Cuprizone
keywords: Auditory cortex; Internal capsule; Long-term potentiation; Neuronal activity