RT Journal Article
T1 Pathway-Specific Control of Striatal Neuron Vulnerability by Corticostriatal Cannabinoid CB1 Receptors
A1 Maroto Martínez, Irene Berenice
A1 Ruiz-Calvo, Andrea
A1 Bajo Grañeras, Raquel
A1 Chiarlone, Anna
A1 Gaudioso, Ángel
A1 Ferrero, José J
A1 Resel, Eva
A1 Sánchez-Prieto Borja, José
A1 Rodríguez Navarro, José Antonio
A1 Marsicano, Giovanni
A1 Galve Roperh, Ismael
A1 Bellocchio, Luigi
A1 Guzmán, Manuel
A1 Guzmán Pastor, Manuel
AB 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.
PB Oxford Academic
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/113489
UL https://hdl.handle.net/20.500.14352/113489
LA eng
NO Ruiz-Calvo A, Maroto IB, Bajo-Grañeras R, Chiarlone A, Gaudioso Á, Ferrero JJ, Resel E, Sánchez-Prieto J, Rodríguez-Navarro JA, Marsicano G, Galve-Roperh I, Bellocchio L, Guzmán M. Pathway-Specific Control of Striatal Neuron Vulnerability by Corticostriatal Cannabinoid CB1 Receptors. Cereb Cortex. 2018 Jan 1;28(1):307-322. doi: 10.1093/cercor/bhx285. PMID: 29121220.
DS Docta Complutense
RD 11 abr 2025