Pathway-Specific Control of Striatal Neuron Vulnerability by Corticostriatal Cannabinoid CB1 Receptors. (31st October 2017)

• Record Type: Journal Article
• Authors: Ruiz-Calvo, Andrea; Maroto, Irene B; Bajo-Grañeras, Raquel; Chiarlone, Anna; Gaudioso, Ángel; Ferrero, José J; Resel, Eva; Sánchez-Prieto, José; Rodríguez-Navarro, José A; Marsicano, Giovanni; Galve-Roperh, Ismael; Bellocchio, Luigi; Guzmán, Manuel
• Is Part Of: Cerebral cortex. Volume 28:Number 1(2018)
• Page Start: 307
• Page End: 322
• Publication Date: 2017-10-31
• Subjects: Cannabinoid receptor -- corticostriatal projection -- huntingtin -- medium spiny neuron -- neuroprotection; Cerebral cortex -- Periodicals; Brain -- Periodicals; 612.825
• DOI: 10.1093/cercor/bhx285
• Languages: English
• ISSNs: 1047-3211

Abstract

Abstract: 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 (D1 R-MSNs), and the indirect pathway, expressing dopamine D2 receptor (D2 R-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 D1 R-MSNs or D2 R-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 (CB1 R) located on corticostriatal terminals efficiently safeguards D1 R-MSNs, but not D2 R-MSNs, from different insults. This cell-specific response relies on the regulation of glutamatergic signaling, and is independent from the CB1 R-dependent control of astroglial activity in the striatum. These findings define cortical CB1 R as a pivotal synaptic player in dictating a differential vulnerability of D1 R-MSNs versus D2 R-MSNs, and increase our understanding of the role of coordinated cannabinergic-glutamatergic signaling in establishing corticostriatal circuits and its dysregulation in neurodegenerative diseases.