2016.06.21
Perinatal Exposure to Neuregulin-1 Results in Disinhibition of Adult Midbrain Dopaminergic Neurons: Implication in Schizophrenia Modeling
(Sci. Rep. 6, 22606; doi: 10.1038/srep22606 (2016))
Hisaaki Namba, Takeshi Okubo & Hiroyuki Nawa
Department of Molecular Neurobiology, Brain Research Institute, Niigata University
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.
