Pathway-Specific Control of Striatal Neuron Vulnerability by Corticostriatal Cannabinoid CB1 Receptors.
Cerebral Cortex. 2017-10-31; 28(1): 307-322
DOI: 10.1093/cercor/bhx285
Lire sur PubMed
1. Cereb Cortex. 2018 Jan 1;28(1):307-322. doi: 10.1093/cercor/bhx285.
Pathway-Specific Control of Striatal Neuron Vulnerability by Corticostriatal
Cannabinoid CB1 Receptors.
Ruiz-Calvo A(1)(2), Maroto IB(1)(2), Bajo-Grañeras R(1)(2), Chiarlone A(1)(2),
Gaudioso Á(2), Ferrero JJ(3), Resel E(1)(2), Sánchez-Prieto J(3),
Rodríguez-Navarro JA(2), Marsicano G(4), Galve-Roperh I(1)(2), Bellocchio L(4),
Guzmán M(1)(2).
Author information:
(1)Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
(CIBERNED), Instituto Universitario de Investigación Neuroquímica (IUIN) and
Department of Biochemistry and Molecular Biology I, Complutense University, 28040
Madrid, Spain.
(2)Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid,
Spain.
(3)Instituto Universitario de Investigación Neuroquímica (IUIN) and Department of
Biochemistry and Molecular Biology IV, Complutense University, 28040 Madrid,
Spain.
(4)INSERM and University of Bordeaux, NeuroCentre Magendie, Physiopathologie de
la Plasticité Neuronale, U1215, 33077 Bordeaux, France.
The vast majority of neurons within the striatum are GABAergic medium spiny
neurons (MSNs), which receive glutamatergic input from the cortex and thalamus,
and form two major efferent pathways: the direct pathway, expressing dopamine D1
receptor (D1R-MSNs), and the indirect pathway, expressing dopamine D2 receptor
(D2R-MSNs). While molecular mechanisms of MSN degeneration have been identified
in animal models of striatal damage, the molecular factors that dictate a
selective vulnerability of D1R-MSNs or D2R-MSNs remain unknown. Here, we combined
genetic, chemogenetic, and pharmacological strategies with behavioral and
neurochemical analyses, and show that the pool of cannabinoid CB1 receptor (CB1R)
located on corticostriatal terminals efficiently safeguards D1R-MSNs, but not
D2R-MSNs, from different insults. This cell-specific response relies on the
regulation of glutamatergic signaling, and is independent from the CB1R-dependent
control of astroglial activity in the striatum. These findings define cortical
CB1R as a pivotal synaptic player in dictating a differential vulnerability of
D1R-MSNs versus D2R-MSNs, and increase our understanding of the role of
coordinated cannabinergic-glutamatergic signaling in establishing corticostriatal
circuits and its dysregulation in neurodegenerative diseases.
© The Author 2017. Published by Oxford University Press.
DOI: 10.1093/cercor/bhx285
PMID: 29121220 [Indexed for MEDLINE]