Original Research ARTICLE
CB1 cannabinoid receptor expression in the striatum: association with corticostriatal circuits and developmental regulation
- Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA
Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains). We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25) and then progressively decreases toward adolescent (P40) and adult (P70) levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors) tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors) receive inputs from cortical regions with higher expression (medial prefrontal cortex). In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important.
Keywords: CB1 cannabinoid receptor, corticostriatal, development, gene expression, striatum
Citation: Van Waes V, Beverley JA, Siman H, Tseng KY and Steiner H (2012) CB1 cannabinoid receptor expression in the striatum: association with corticostriatal circuits and developmental regulation. Front. Pharmacol. 3:21. doi: 10.3389/fphar.2012.00021
Received: 12 October 2011; Accepted: 07 February 2012;
Published online: 12 March 2012.
Edited by:Joseph F. Cheer, University of Maryland School of Medicine, USA
Reviewed by:David M. Lovinger, National Institutes of Health, USA
Jason B. Wu, Cedars-Sinai Medical Center, USA
Miles Herkenham, National Institutes of Health, USA
Copyright: © 2012 Van Waes, Beverley, Siman, Tseng and Steiner. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Heinz Steiner, Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. e-mail: email@example.com
†Present address: Vincent Van Waes, Laboratory of Integrative and Clinical Neurosciences, University of Franche-Comté, 25000 Besançon, France