RT Journal Article
SR Electronic
T1 Cannabinoid Receptor 1 Is Required for Neurodevelopment of Striosome-Dendron Bouquets
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0318-21.2022
DO 10.1523/ENEURO.0318-21.2022
VO 9
IS 2
A1 Jill R. Crittenden
A1 Tomoko Yoshida
A1 Samitha Venu
A1 Ara Mahar
A1 Ann M. Graybiel
YR 2022
UL http://www.eneuro.org/content/9/2/ENEURO.0318-21.2022.abstract
AB Cannabinoid receptor 1 (CB1R) has strong effects on neurogenesis and axon pathfinding in the prenatal brain. Endocannabinoids that activate CB1R are abundant in the early postnatal brain and in mother’s milk, but few studies have investigated their function in newborns. We examined postnatal CB1R expression in the major striatonigral circuit from striosomes of the striatum to the dopamine-containing neurons of the substantia nigra. CB1R enrichment was first detectable between postnatal day (P)5 and P7, and this timing coincided with the formation of “striosome-dendron bouquets,” the elaborate anatomic structures by which striosomal neurons control dopaminergic cell activity through inhibitory synapses. In Cnr1−/− knock-out mice lacking CB1R expression, striosome-dendron bouquets were markedly disorganized by P11 and at adulthood, suggesting a postnatal pathfinding connectivity function for CB1R in connecting striosomal axons and dopaminergic neurons analogous to CB1R’s prenatal function in other brain regions. Our finding that CB1R plays a major role in postnatal wiring of the striatonigral dopamine-control system, with lasting consequences at least in mice, points to a crucial need to determine whether lactating mothers’ use of CB1R agonists (e.g., in marijuana) or antagonists (e.g., type 2 diabetes therapies) can disrupt brain development in nursing offspring.