Cannabinoid Receptor Type 1 regulates growth cone filopodia and axon dispersion in the optic tract of Xenopus laevis tadpoles.

Previous studies show that the main cannabinoid receptor in the brain-cannabinoid type 1 receptor (CB1R)-is required for establishment of axonal projections in developing neurons but questions remain regarding the cellular and molecular mechanisms, especially in neurons developing in their native environment. We assessed the effects of CB1R signalling on growth cone filopodia and axonal projections of retinal ganglion cells (RGCs) in whole mount brains from Xenopus laevis tadpoles. Our results indicate that growth cones of RGC axons in brains from tadpoles exposed to a CB1R agonist had fewer filopodial protrusions, whereas growth cones from tadpoles exposed to a CB1R inverse agonist had more filopodia than growth cones of RGC axons in whole brains from control tadpoles. However, application of both the CB1R agonist and inverse agonist resulted in RGC axons that were overly dispersed and undulatory in the optic tract in situ. In addition, expression of a mutant for cadherin adhesive factor, ß-catenin, that disrupts its binding to α-catenin, and application of an inhibitor for actin regulator non-muscle Myosin II, phenocopied the effects of the CB1R agonist and inverse agonist on growth cone filopodia, respectively. These findings suggest that both destablization and stabilization of growth cone filopodia are required for RGC axonal fasciculation/defasciculation in the optic tract and that CB1R regulates growth cone filopodia and axon dispersion of RGCs by oppositely modulating ß-catenin adhesive and Myosin II actin regulatory functions. This study extends and confirms our understanding of cannabinoid mechanisms in sculpting developing neuronal circuits in vivo.

A Case Series: Successfully Preventing COVID-19 Outbreak in a Residential Community Setting at a Drug and Alcohol Addiction Treatment Center.

Coronavirus disease 2019 (COVID-19) has reduced the capacity of many addiction treatment centers, limiting access to safe, continual treatment for people with substance use disorders (SUD) in the setting of a pandemic. Here, we describe the COVID-19 screening process of a residential addiction treatment center in rural Connecticut that has had no outbreaks, closures, or reductions in capacity since the pandemic began. Out of 420 patients screened for COVID-19 from 1 February to 1 July, five patients tested positive for COVID-19: four prior to entering its residential community setting, and one after entering the residential community, resulting in no COVID-19 spread to other patients. Patient 1 presented from home and tested positive during screening prior to entry into the community. The primary care provider for patient 2 notified staff of a recent pos-itive COVID-19 test prior to the patient's arrival on-site. Patient 3 had a COVID-19 infection in the weeks prior to arrival and tested positive during initial screening. Patient 4 tested positive af-ter coming from another addiction treatment facility that was shut down due to a COVID-19 outbreak. Patient 5 tested negative for COVID-19 during initial screening, entered the residential community, and later tested positive. It is imperative that in-person support for SUD continues during the pandemic. This case report highlights the importance of implementing a variety of tools in an effective screening process, including polymerase chain reaction screening and daily symptomology and temperature screening, which may help prevent further closures or reductions in capacity of addiction treatment centers during the COVID-19 pandemic or future outbreaks.