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The endocannabinoid (eCB) signaling system has been functionally implicated in many brain regions. Our understanding of the role of cannabinoid receptor type 1 (CB 1 ) in olfactory processing remains limited. Cannabinoid signaling is involved in regulating glomerular activity in the main olfactory bulb (MOB). However, the cannabinoid-related circuitry of inputs to mitral cells in the MOB has not been fully determined. Using anatomical and functional approaches we have explored this question. CB 1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons but not in mitral cells. We detected eCBs in the mouse MOB as well as the expression of CB 1 and other genes associated with cannabinoid signaling in the MOB. Patch-clamp electrophysiology demonstrated that CB 1 agonists activated mitral cells and evoked an inward current, while CB 1 antagonists reduced firing and evoked an outward current. CB 1 effects on mitral cells were absent in subglomerular slices in which the olfactory nerve layer and glomerular layer were removed, suggesting the glomerular layer as the site of CB 1 action. We previously observed that GABAergic periglomerular cells show the inverse response pattern to CB 1 activation compared with mitral cells, suggesting that CB 1 indirectly regulates mitral cell activity as a result of cellular activation of glomerular GABAergic processes . This hypothesis was supported by the finding that cannabinoids modulated synaptic transmission to mitral cells. We conclude that CB 1 directly regulates GABAergic processes in the glomerular layer to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior. NEW &amp; NOTEWORTHY Cannabinoid signaling with cannabinoid receptor type 1 (CB 1 ) is involved in the regulation of glomerular activity in the main olfactory bulb (MOB). We detected endocannabinoids in the mouse MOB. CB 1 was present in periglomerular processes of a GAD65-positive subpopulation of interneurons. CB 1 agonists activated mitral cells. CB 1 directly regulates GABAergic processes to control GABA release and, in turn, regulates mitral cell activity with potential effects on olfactory threshold and behavior.

Cannabinoid receptor-mediated modulation of inhibitory inputs to mitral cells in the main olfactory bulb