Subcellular specificity of cannabinoid effects in striatonigral circuits.
Neuron. 2021-03-01; :
DOI: 10.1016/j.neuron.2021.03.007
Read on PubMed
Soria-Gomez E(1), Pagano Zottola AC(2), Mariani Y(2), Desprez T(2), Barresi M(3), Bonilla-Del Río I(4), Muguruza C(5), Le Bon-Jego M(3), Julio-Kalajzić F(2), Flynn R(6), Terral G(2), Fernández-Moncada I(2), Robin LM(2), Oliveira da Cruz JF(2), Corinti S(2), Amer YO(7), Goncalves J(2), Varilh M(2), Cannich A(2), Redon B(2), Zhao Z(2), Lesté-Lasserre T(2), Vincent P(2), Tolentino-Cortes T(8), Busquets-García A(2), Puente N(4), Bains JS(9), Hebert-Chatelain E(7), Barreda-Gómez G(8), Chaouloff F(2), Lohman AW(10), Callado LF(11), Grandes P(12), Baufreton J(3), Marsicano G(13), Bellocchio L(14).
Author information:
(1)INSERM, U1215 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, France; University of Bordeaux, Bordeaux, France; Department of
Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain; Achucarro Basque Center for Neuroscience, Leioa, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. Electronic address: .
(2)INSERM, U1215 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, France; University of Bordeaux, Bordeaux, France.
(3)University of Bordeaux, Bordeaux, France; IMN-UMR CNRS 5293 Neurodegenerative Diseases Institute, Bordeaux, France.
(4)Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain; Achucarro Basque Center for Neuroscience, Leioa, Spain.
(5)Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
(6)Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
(7)Canada Research Chair in Mitochondrial Signaling and Physiopathology, Department of Biology, University of Moncton, Moncton, NB, Canada.
(8)Department of Research and Development, IMG Pharma Biotech S.L., Derio, Spain.
(9)Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
(10)Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
(11)Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
(12)Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain; Achucarro Basque Center for Neuroscience, Leioa, Spain; Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
(13)INSERM, U1215 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, France; University of Bordeaux, Bordeaux, France. Electronic address:
(14)INSERM, U1215 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, Bordeaux, France; University of Bordeaux, Bordeaux, France. Electronic address:
Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors. Pharmacological activation of type 1 cannabinoid (CB1) receptors in the striatonigral circuit elicits both antinociception and catalepsy in mice. The decrease in nociception depends on the activation of plasma membrane-residing CB1 receptors (pmCB1), leading to the inhibition of cytosolic PKA activity and substance P release. By contrast, mitochondrial-associated CB1 receptors (mtCB1) located at the same terminals mediate cannabinoid-induced catalepsy through the decrease in intra-mitochondrial PKA-dependent cellular respiration and synaptic transmission. Thus, subcellular-specific CB1 receptor signaling within striatonigral circuits determines multimodal control of behavior.
Copyright © 2021. Published by Elsevier Inc.