PT  - JOURNAL ARTICLE
AU  - Jill R. Crittenden
AU  - Tomoko Yoshida
AU  - Samitha Venu
AU  - Ara Mahar
AU  - Ann M. Graybiel
TI  - Cannabinoid Receptor 1 Is Required for Neurodevelopment of Striosome-Dendron Bouquets
AID  - 10.1523/ENEURO.0318-21.2022
DP  - 2022 Mar 01
TA  - eneuro
PG  - ENEURO.0318-21.2022
VI  - 9
IP  - 2
4099  - http://www.eneuro.org/content/9/2/ENEURO.0318-21.2022.short
4100  - http://www.eneuro.org/content/9/2/ENEURO.0318-21.2022.full
SO  - eNeuro2022 Mar 01; 9
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.