Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors.

Department of Physiology and Biophysics, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY 14214, USA.

Proceedings of the National Academy of Sciences of the United States of America 2010 Dec 21

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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.

Citation

Eunice Y Yuen, Ping Zhong, Zhen Yan. Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors. Proceedings of the National Academy of Sciences of the United States of America. 2010 Dec 21;107(51):22308-13