Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19115-20. Epub 2005 Dec 15.

Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor.

Author information

1
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Scheeles väg 1:A1, Karolinska Institutet, S-17177 Stockholm, Sweden.

Abstract

In utero exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the active component from marijuana, induces cognitive deficits enduring into adulthood. Although changes in synaptic structure and plasticity may underlie Delta(9)-THC-induced cognitive impairments, the neuronal basis of Delta(9)-THC-related developmental deficits remains unknown. Using a Boyden chamber assay, we show that agonist stimulation of the CB(1) cannabinoid receptor (CB(1)R) on cholecystokinin-expressing interneurons induces chemotaxis that is additive with brain-derived neurotrophic factor (BDNF)-induced interneuron migration. We find that Src kinase-dependent TrkB receptor transactivation mediates endocannabinoid (eCB)-induced chemotaxis in the absence of BDNF. Simultaneously, eCBs suppress the BDNF-dependent morphogenesis of interneurons, and this suppression is abolished by Src kinase inhibition in vitro. Because sustained prenatal Delta(9)-THC stimulation of CB(1)Rs selectively increases the density of cholecystokinin-expressing interneurons in the hippocampus in vivo, we conclude that prenatal CB(1)R activity governs proper interneuron placement and integration during corticogenesis. Moreover, eCBs use TrkB receptor-dependent signaling pathways to regulate subtype-selective interneuron migration and specification.

PMID:
16357196
PMCID:
PMC1323195
DOI:
10.1073/pnas.0509494102
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center