Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors.
Alterations of synaptic transmission have been considered a core feature of mental disorders; thus, we examined the role of dopamine D(4) receptors, which is highly implicated in attention-deficit hyperactivity disorder and schizophrenia, in regulating synaptic functions of prefrontal cortex, a brain region critical for cognitive and emotional processes. We found that D(4) stimulation caused a profound depression or potentiation of AMPA receptor-mediated excitatory synaptic transmission in prefrontal cortex pyramidal neurons when their activity was elevated or dampened, respectively, which was accompanied by a D(4)-induced decrease or increase of AMPARs at synapses. The dual effects of D(4) on AMPAR trafficking and function was dependent on the D(4)-mediated bidirectional regulation of CaMKII activity via coupling to distinct signaling pathways, which provides a unique mechanism for D(4) receptors to serve as a homeostatic synaptic factor to stabilize cortical excitability.
Department of Physiology and Biophysics, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY 14214, USA.
Eunice Y
EY
Yuen
Ping
P
Zhong
Zhen
Z
Yan
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D021381:Protein Transport / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D050638:Receptors, Dopamine D4; D018698:Glutamic Acid