Homeostatic regulation of glutamatergic transmission by dopamine D4 receptors.

Abstract

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.

• Authors: Eunice Y Yuen, Ping Zhong, Zhen Yan
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 107 Issue 51 Pg. 22308-13 (Dec 21 2010) ISSN: 1091-6490 [Electronic] United States
• PMID: 21135234 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Receptors, Dopamine D4
• Glutamic Acid

Topics

• Animals
• Attention Deficit Disorder with Hyperactivity (metabolism)
• Glutamic Acid (metabolism)
• Homeostasis (physiology)
• Humans
• Protein Transport (physiology)
• Pyramidal Cells (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Dopamine D4 (metabolism)
• Schizophrenia (metabolism)
• Synapses (metabolism)
• Synaptic Transmission (physiology)