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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
Author(s) -
Fitzgerald Megan L.,
Chan June,
Mackie Kenneth,
Lupica Carl R.,
Pickel Virginia M.
Publication year - 2012
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23141
Subject(s) - parvalbumin , biology , interneuron , prefrontal cortex , dopamine receptor d2 , neuroscience , dopamine , cannabinoid receptor , neurotransmission , dendrite (mathematics) , inhibitory postsynaptic potential , receptor , microbiology and biotechnology , biochemistry , cognition , agonist , geometry , mathematics
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. J. Comp. Neurol. 520:4013–4031, 2012. © 2012 Wiley Periodicals, Inc.