title: Perinatal Exposure to Neuregulin-1 Results in Disinhibition of Adult Midbrain Dopaminergic Neurons: Implication in Schizophrenia Modeling.
abstract: Aberrant neuregulin-1 (NRG1) signals are suggested to associate with the neuropathophysiology of schizophrenia. Employing a mouse schizophrenia model established by neonatal neuregulin-1 challenge, we analysed postpubertal consequence of the NRG1 pretreatment for the electrophysiological property of nigral dopamine neurons. In vivo single unit recordings from anaesthetized NRG1-pretreated mice revealed increased spike bursting of nigral dopamine neurons. In slice preparations from NRG1-pretreated mice, spontaneous firing was elevated relative to controls. The relative increase in firing rates was abolished by a GABAA receptor antagonist. Whole-cell recording showed that perinatal NRG1 pretreatment diminished inhibitory miniature synaptic currents as well as GABAA receptor sensitivity. These results collectively suggest that perinatal exposure to neuregulin-1 results in the disinhibition of nigral dopamine neurons to influence their firing properties at the adult stage when the behavioral deficits are evident.
authors.affiliation: Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Namba
authors.affiliation: Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okubo
authors.affiliation: Department of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008636:Mesencephalon / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D020890:Neuregulin-1 / Q000633:toxicity*; D011963:Receptors, GABA-A / Q000378:metabolism; D012559:Schizophrenia / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D058787:GABA-A Receptor Antagonists; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D011963:Receptors, GABA-A