Immunohistochemical description of the endogenous cannabinoid system in the rat cerebellum and functionally related...

We report a detailed analysis of the distribution of relevant proteins of the endogenous cannabinoid system in the rat cerebellum (cerebellar cortex and deep cerebellar nuclei) and the two functionally related nuclei, the vestibular nuclei and the inferior olive. These proteins include the two main cannabinoid receptors (CB(1) and CB(2)), the enzymes involved in cannabinoid biosynthesis (DAGL alpha, DAGL beta, and NAPE-PLD), and the endocannabinoid-degradating enzymes (FAAH and MAGL). With regard to the cerebellar cortex, these data confirm several published reports on the distribution of cannabinoid CB(1) receptors, DAGL alpha, MAGL, and FAAH, which suggests a role of endocannabinoids as retrograde messengers in the synapses of the Purkinje cells by either parallel fibers of granule cells or climbing fibers from the inferior olive or GABAergic interneuron. Additionally, we describe the presence of CB(2) receptors in fibers related to Purkinje somata (Pinceau formations) and dendrites (parallel fibers), suggesting a potential role of this receptor in the retrograde cannabinoid signaling. A remarkable finding of the present study is the description of the different elements of the endogenous cannabinoid system in both the main afferent nuclei to the cerebellar cortex (the inferior olive) and the efferent cerebellar pathway (the deep cerebellar nuclei). The presence of the endogenous cannabinoid system at this level establishes the basis for endocannabinoid-mediated synaptic plasticity as a control mechanism in motor learning, opening new research lines for the study of the contribution of this system in gait disorders affecting the cerebellum.