Gene Wakeup Calls from the Locus Ceruleus

Dopamine and some other neuromodulators are thought to act by volumetric signaling (i.e., gradient diffusion of neurotransmitter to receptors beyond a synaptic release site). In this issue, Paspalas and Goldman-Rakic outline such a signaling pathway involving the D5 dopamine receptor. They used immunogold labeling and electron microscopy in pyramidal neurons of monkey prefrontal cortex. Specific signaling cascades presumably require cytosolic compartmentalization of signaling molecules and a physical scaffold for downstream effector molecules. The authors report a tight anatomical link between membrane D5 receptors in the perisomatic region and subsurface cisterns (SSCs) containing calcium and inositol 1,4,5-trisphosphate (InsP) receptors. SSCs were confined to the perisomatic regions and were not seen in nonpyramidal neurons. Likewise, D5 receptors appeared to be exclusively expressed outside of the synapse. Thus D5 receptors in plasma membrane closely apposed to SSC and mitochondrial membranes provide a plausible mechanism for, as the authors put it, “diffuse” dopaminergic transmission.