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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

Authors

  • Megan L. Fitzgerald,

    1. Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10065
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  • June Chan,

    1. Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10065
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  • Kenneth Mackie,

    1. Department of Psychological & Brain Sciences and the Gill Center, Indiana University, Bloomington, Indiana 47405
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  • Carl R. Lupica,

    1. Electrophysiology Research Section, Cellular Neurobiology Branch, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland 21224
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  • Virginia M. Pickel

    Corresponding author
    1. Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York 10065
    • Division of Neurobiology, Weill Cornell Medical College, 407 East 61st St., New York, NY 10065
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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. J. Comp. Neurol. 520:4013–4031, 2012. © 2012 Wiley Periodicals, Inc.

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