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The Journal of Neuroscience, June 9, 2004, 24(23):5292-5300; doi:10.1523/JNEUROSCI.0195-04.2004

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Cellular/Molecular
Microdomains for Dopamine Volume Neurotransmission in Primate Prefrontal Cortex

Constantinos D. Paspalas and Patricia S. Goldman-Rakic 

The explicit yet enigmatic involvement of dopamine in cortical physiology is in part volumetric (beyond the synapse), as is apparently the action of neuroleptics targeting dopamine receptors. The notion that nonsynaptic neuronal membranes would translate extracellular dopamine into receptor-specific spatiotemporal downstream signaling, similar to the chemical synapse, is intriguing. Here, we report that dopamine D₅ (but not D₁ or D₂) receptors in the perisomatic plasma membrane of prefrontal cortical neurons form discrete and exclusively extrasynaptic microdomains with inositol 1,4,5-trisphosphate-gated calcium stores of subsurface cisterns and mitochondria. These findings introduce a novel dopaminoceptive substratum in the brain and a unique D₅ receptor-specific signaling paradigm.

Key words: dopamine receptor; InsP3 receptor; subsurface cistern; electron microscopy; neuronal calcium; microdomain; prefrontal cortex; working memory

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Received Jan 18, 2004; revised April 1, 2004; accepted April 29, 2004.

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