Abstract
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.
Highlights
Anatomical circuits interconnecting the cerebral cortex and the basal ganglia are critical for the organization of goal-directed behavior, and dysfunction in these circuits is associated with numerous brain disorders, ranging from movement disorders to obsessive compulsive disorder, schizophrenia, and drug addiction, depending on the particular circuits affected (e.g., Albin et al, 1989; DeLong, 1990; Hyman and Nestler, 1996; Graybiel and Rauch, 2000; Steiner, 2010)
We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats
Anatomical circuits interconnecting the cerebral cortex and the basal ganglia are critical for the organization of goal-directed behavior, and dysfunction in these circuits is associated with numerous brain disorders, ranging from movement disorders to obsessive compulsive disorder, schizophrenia, and drug addiction, depending on the particular circuits affected (e.g., Albin et al, 1989; DeLong, 1990; Hyman and Nestler, 1996; Graybiel and Rauch, 2000; Steiner, 2010)
Summary
Anatomical circuits interconnecting the cerebral cortex and the basal ganglia are critical for the organization of goal-directed behavior, and dysfunction in these circuits is associated with numerous brain disorders, ranging from movement disorders to obsessive compulsive disorder, schizophrenia, and drug addiction, depending on the particular circuits affected (e.g., Albin et al, 1989; DeLong, 1990; Hyman and Nestler, 1996; Graybiel and Rauch, 2000; Steiner, 2010). Cortico-basal ganglia circuits arise from all parts of the cortex and project in a topographical manner to the striatum (caudate–putamen, nucleus accumbens), and from there, via basal ganglia output nuclei and thalamus, back to the cortex (Alexander et al, 1986, 1990; Albin et al, 1989; Groenewegen et al, 1990; Joel and Weiner, 1994). Activity within these circuits is modulated by a variety of G-protein-coupled receptors. Lower levels of CB1 receptors are present throughout the cortex (Herkenham et al, 1991b; Mailleux and Vanderhaeghen, 1992; Matsuda et al, 1993; Heng et al, 2011), including in corticostriatal neurons (Uchigashima et al, 2007)
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