Cannabinoid Receptor 1 Is Required for Neurodevelopment of Striosome-Dendron Bouquets
Name
ENEURO.0318-21.2022.full.pdf
Description
Published version
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7.25 MB
Format
Adobe PDF
Checksum (MD5)
a995816eb89c5dd78e14500eb035424d
Author(s)
Crittenden, Jill R
Yoshida, Tomoko
Venu, Samitha
Mahar, Ara
Graybiel, Ann M
Date Issued
2022
Journal
eneuro
Publisher
Society for Neuroscience
Citation
Crittenden, Jill R, Yoshida, Tomoko, Venu, Samitha, Mahar, Ara and Graybiel, Ann M. 2022. "Cannabinoid Receptor 1 Is Required for Neurodevelopment of Striosome-Dendron Bouquets." eneuro, 9 (2).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1523/ENEURO.0318-21.2022
