Cell type specific cannabinoid CB1 receptor distribution across the human and non-human primate cortex

Abstract

Alterations in cannabinoid CB1 receptor (CB1R) are implicated in various psychiatric disorders. CB1R participates in both depolarization induced suppression of inhibition (DSI) and depolarization induced suppression of excitation (DSE), suggesting its involvement in regulating excitatory and inhibitory (E/I) balance. Prior studies examining neuronal cell type specific CB1R distribution have been conducted near exclusively within rodents. Identification of these distribution patterns within the human and non-human primate cortex is essential to increase our insight into its function. Using co-labeling immunohistochemistry and fluorescent microscopy, we examined CB1R protein levels within excitatory and inhibitory boutons of male human and non-human primate prefrontal cortex and auditory cortices, regions involved in the behavioral effects of exogenous cannabinoid exposures. We found that CB1R was present in both bouton populations within all brain regions examined in both species. Significantly higher CB1R levels were found within inhibitory than within excitatory boutons across all regions in both species, although the cell type by brain region interactions differed between the two species. Our results support the importance of conducting more in-depth CB1R examinations to understand how cell type and brain region dependent differences contribute to regional E/I balance regulation, and how aberrations in CB1R distribution may contribute to pathology.

Modulation of Astroglial Glutamate Transporters by CB1 Receptor Shapes Endocannabinoid-Mediated Long-Term Depression in the Medial Prefrontal Cortex

“…1a, b & d). The wide distribution and staining pattern of CB1R in the cortical layers evaluated was aligned with the existing literature for other brain regions 43 . Speci cally, our analysis revealed a positive colocalization with CB1R, con rming its expression by astrocytes in the cortical layers examined of the mPFC (Fig.…”

Regular cannabis use modulates the impact of HIV on the neural dynamics serving cognitive control

“…Cannabis is one of the most commonly used psychotropic substances in the United States (Azofeifa et al, 2016; Carliner et al, 2017) and its main psychoactive component is ∆ 9 -tetrahydrocannabinol (Bloomfield et al, 2019; Chou et al, 2022), which serves as an agonist of the endocannabinoid CB 1 and CB 2 receptors (Howlett and Abood, 2017). Cannabis has been shown to reduce inflammation in PWH (Ellis et al, 2020, 2021; Manuzak et al, 2018) by acting on CB 2 receptors found primarily on immune cells that modulate the release of inflammatory cytokines (Hall and Degenhardt, 2009; Skosnik et al, 2016).…”

Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: a pilot study

“…We previously demonstrated successful and specific vGAT and vGlut1 labeling in human and non-human primate postmortem studies using these antibodies (48)(49)(50)(51). The CB1R antibody demonstrated successful co-labeling with both vGAT and vGlut1 in both neuronal cultures and postmortem human brain samples (21,52). In addition, vGAT and CB1R antibody specificities were validated through knockout samples (53,54), and vGlut1 antibody through pre-adsorption controls (Millipore certificate of analysis, 2016).…”

“…A ubiquitous G-protein coupled receptor (GPCR) (17), CB1R is highly expressed within the cholecystokinin (CCK) subtype GABAergic inhibitory interneurons within the human cortex (18,19). However, it is also found in other interneuronal subtypes and glutamatergic neurons (20,21). Functionally, presynaptic CB1R activation results in reduced synaptic transmission by attenuating neurotransmitter release, a phenomenon known as depolarization-induced suppression of inhibition (DSI) at inhibitory boutons, and depolarization-induced suppression of excitation (DSE) at excitatory sites (22)(23)(24).…”

“…We hypothesized that the discrepant results between these two methods may stem from Terminal type-specific alterations of CB1R levels in SZ. We undertook to preliminarily test this idea by performing quantitative IHC using a CB1R antibody we previously showed to detect CB1R in both interneurons and glutamatergic neurons in the postmortem human PFC (21), in an existing cohort of SZ subjects previously examined with both ligand-binding autoradiography and CCK cell selective CB1R antibodies.…”