Pathway-Specific Control of Striatal Neuron Vulnerability by Corticostriatal Cannabinoid CB1 Receptors
| Autor: | Anna Chiarlone, Giovanni Marsicano, Jose A. Rodriguez-Navarro, Andrea Ruiz-Calvo, Irene B. Maroto, José Sánchez-Prieto, Manuel Guzmán, Luigi Bellocchio, José Javier Ferrero, Eva Resel, Ismael Galve-Roperh, Angel Gaudioso, Raquel Bajo-Grañeras |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cell Survival Cognitive Neuroscience Genetic Vectors Glutamic Acid Mice Transgenic Striatum Biology Indirect pathway of movement Medium spiny neuron Synaptic Transmission 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic 0302 clinical medicine Dopamine receptor D1 Neurochemical Receptor Cannabinoid CB1 Dopamine receptor D2 Neural Pathways Animals Humans Direct pathway of movement Cerebral Cortex Neurons Huntingtin Protein Receptors Dopamine D2 Receptors Dopamine D1 Corpus Striatum Disease Models Animal Huntington Disease 030104 developmental biology Astrocytes Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cerebral Cortex. 28:307-322 |
| ISSN: | 1460-2199 1047-3211 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|