title: Altered dendritic distribution of dopamine D2 receptors and reduction in mitochondrial number in parvalbumin-containing interneurons in the medial prefrontal cortex of cannabinoid-1 (CB1) receptor knockout mice.
abstract: The prelimbic prefrontal cortex (PL) is a brain region integral to complex behaviors that are highly influenced by cannabinoids and by dopamine D2 receptor (D2R)-mediated regulation of fast-firing parvalbumin-containing interneurons. We have recently shown that constitutive deletion of the cannabinoid-1 receptor (CB1R) greatly reduces parvalbumin levels in these neurons. The effects of CB1R deletion on PL parvalbumin interneurons may be ascribed to loss of CB1R-mediated retrograde signaling on mesocortical dopamine transmission, and, in turn, altered expression and/or subcellular distribution of D2R in the PL. Furthermore, diminished parvalbumin expression could indicate metabolic changes in fast-firing interneurons that may be reflected in changes in mitochondrial density in this population. We therefore comparatively examined electron microscopic dual labeling of D2R and parvalbumin in CB1 (-/-) and CB1 (+/+) mice to test the hypothesis that absence of CB1R produces changes in D2R localization and mitochondrial distribution in parvalbumin-containing interneurons of the PL. CB1 (-/-) mice had a significantly lower density of cytoplasmic D2R-immunogold particles in medium parvalbumin-labeled dendrites and a concomitant increase in the density of these particles in small dendrites. These dendrites received both excitatory and inhibitory-type synapses from unlabeled terminals and contained many mitochondria, whose numbers were significantly reduced in CB1 (-/-) mice. Non-parvalbumin dendrites showed no between-group differences in either D2R distribution or mitochondrial number. These results suggest that cannabinoid signaling provides an important determinant of dendritic D2 receptor distribution and mitochondrial availability in fast-spiking interneurons.
authors.affiliation: Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Fitzgerald
authors.forename: June
authors.initials: J
authors.lastname: Chan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mackie
authors.forename: Carl R
authors.initials: CR
authors.lastname: Lupica
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Pickel
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000648:ultrastructure*; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism / Q000648:ultrastructure; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: C543264:Cnr1 protein, rat; D010320:Parvalbumins; D043884:Receptor, Cannabinoid, CB1; D017448:Receptors, Dopamine D2