Microdomains for dopamine volume neurotransmission in primate prefrontal cortex.
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.
Paspalas
Constantinos D
CD
Yale University School of Medicine, Department of Neurobiology, Sterling Hall of Medicine B408, 333 Cedar Street, New Haven, CT 0651, USA. constantinos.paspalas@yale.edu
Goldman-Rakic
Patricia S
PS
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008253:Macaca mulatta; D021962:Membrane Microdomains / Q000378:metabolism / Q000502:physiology*; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000378:metabolism / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050641:Receptors, Dopamine D5; D015398:Signal Transduction; D009435:Synaptic Transmission
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050641:Receptors, Dopamine D5; D004298:Dopamine