title: Restoration of glutamatergic transmission by dopamine D4 receptors in stressed animals.
abstract: The prefrontal cortex (PFC), a key brain region for cognitive and emotional processes, is highly regulated by dopaminergic inputs. The dopamine D4 receptor, which is enriched in PFC, has been implicated in mental disorders, such as attention deficit-hyperactivity disorder and schizophrenia. Recently we have found homeostatic regulation of AMPA receptor-mediated synaptic transmission in PFC pyramidal neurons by the D4 receptor, providing a potential mechanism for D4 in stabilizing cortical excitability. Because stress is tightly linked to adaptive and maladaptive changes associated with mental health and disorders, we examined the synaptic actions of D4 in stressed rats. We found that neural excitability was elevated by acute stress and dampened by repeated stress. D4 activation produced a potent reduction of excitatory transmission in acutely stressed animals and a marked increase of excitatory transmission in repeatedly stressed animals. These effects of D4 targeted GluA2-lacking AMPA receptors and relied on the bi-directional regulation of calcium/calmodulin kinase II activity. The restoration of PFC glutamatergic transmission in stress conditions may enable D4 receptors to serve as a synaptic stabilizer in normal and pathological conditions.
authors.affiliation: From the Department of Physiology and Biophysics, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York 14214.
authors.forename: Eunice Y
authors.initials: EY
authors.lastname: Yuen
authors.affiliation: From the Department of Physiology and Biophysics, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York 14214.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhong
authors.affiliation: From the Department of Physiology and Biophysics, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York 14214.
authors.forename: Xiangning
authors.initials: X
authors.lastname: Li
authors.affiliation: From the Department of Physiology and Biophysics, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York 14214.
authors.forename: Jing
authors.initials: J
authors.lastname: Wei
authors.affiliation: From the Department of Physiology and Biophysics, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York 14214. Electronic address: zhenyan@buffalo.edu.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
mesh_terms: D000818:Animals; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission
chemical_list: D018091:Receptors, AMPA; D050638:Receptors, Dopamine D4; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Calcium/Calmodulin-dependent Protein Kinase (CaMK); Dopamine Receptors; Glutamate Receptors, Ionotropic (AMPA, NMDA); Neurophysiology; Stress