title: Modulation of inhibitory activity markers by intermittent theta-burst stimulation in rat cortex is NMDA-receptor dependent.
abstract: BACKGROUND
  Intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation has been shown to increase cortical excitability in humans. In the rat brain it strongly reduced the number of neurons expressing the 67-kD isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and those expressing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), specific markers of fast-spiking (FS) and non-FS inhibitory interneurons, respectively, an indication of modified cortical inhibition.
  
  
  OBJECTIVE
  Since iTBS effects in humans have been shown to be NMDA receptor sensitive, we wondered whether the iTBS-induced changes in the molecular phenotype of interneurons may be also sensitive to glutamatergic synaptic transmission mediated by NMDA receptors.
  
  
  METHODS
  In a sham-controlled fashion, five iTBS-blocks of 600 stimuli were applied to rats either lightly anesthetized by only urethane or by an additional low (subnarcotic) or high dose of the NMDA receptor antagonist ketamine before immunohistochemical analysis.
  
  
  RESULTS
  iTBS reduced the number of neurons expressing GAD67, PV and CB. Except for CB, a low dose of ketamine partially prevented these effects while a higher dose almost completely abolished the iTBS effects.
  
  
  CONCLUSIONS
  Our findings indicate that iTBS modulates the molecular, and likely also the electric, activity of cortical inhibitory interneurons and that the modulation of FS-type but less that of non-FS-type neurons is mediated by NMDA receptors. A combination of iTBS with pharmacological interventions affecting distinct receptor subtypes may thus offer options to enhance its selectivity in modulating the activity of distinct cell types and preventing others from being modulated.
authors.affiliation: Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, D-44780 Bochum, Germany; Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, D-44791 Bochum, Germany.
authors.forename: Adnan
authors.initials: A
authors.lastname: Labedi
authors.affiliation: Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, D-44780 Bochum, Germany; Department of Cognitive Neurology, Hertie-Institute for Clinical Brain Research, Centre for Integrative Neuroscience, University of Tübingen, Germany.
authors.forename: Alia
authors.initials: A
authors.lastname: Benali
authors.affiliation: Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Mix
authors.affiliation: Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, D-44780 Bochum, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Neubacher
authors.affiliation: Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, D-44780 Bochum, Germany. Electronic address: klaus.funke@rub.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Funke
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology*; D005625:Frontal Lobe / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission; D013826:Theta Rhythm / Q000502:physiology*; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
chemical_list: D064026:Calbindins; D010320:Parvalbumins; D020033:Protein Isoforms; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D005968:Glutamate Decarboxylase
keywords: Calcium-binding proteins; GAD67; Inhibitory systems; Neocortex; c-Fos