A Disynaptic Circuit in the Globus Pallidus Controls Locomotion Inhibition

Autor: Massimo Barresi, Nicolas Mallet, Lise Guilhemsang, Jérôme Baufreton, Asier Aristieta, Stéphanie Fioramonti, Sophie Gauthier, Gilles Courtand, Shiva Azizpour Lindi, Grégory Barrière, Brice de la Crompe
Přispěvatelé: Neurodegeneratives Diseases Institute (IMN-UMR CNRS 5293), Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), IMN (UMR 5293), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2020
Předmět:
Zdroj: Current Biology-CB
Current Biology-CB, Elsevier, In press, ⟨10.1016/j.cub.2020.11.019⟩
ISSN: 1879-0445
0960-9822
Popis: Basal ganglia (BG) inhibit movement through two independent pathways, the indirect- and the hyperdirect-pathways. The globus pallidus (GP) has always been viewed as a simple relay within these two pathways, but its importance has changed drastically with the discovery of two functionally-distinct cell types, namely the prototypic and the arkypallidal neurons. Classic BG models suggest that all GP neurons receive GABAergic inputs from striato-pallidal indirect spiny projection neurons and glutamatergic inputs from subthalamic neurons. However, whether this synaptic connectivity scheme applies to both GP cell-types is currently unknown. Here, we optogenetically dissect the input organization of prototypic and arkypallidal neurons and further define the circuit mechanism underlying action inhibition in BG. Our results highlight that an increased activity of arkypallidal neurons is required to inhibit locomotion. Finally, this work supports the view that arkypallidal neurons are part of a novel disynaptic feedback loop that broadcast inhibitory control on movement execution.; Basal ganglia (BG) inhibit movement through two independent pathways, the indirect- and the hyperdirect-pathways. The globus pallidus (GP) has always been viewed as a simple relay within these two pathways, but its importance has changed drastically with the discovery of two functionally-distinct cell types, namely the prototypic and the arkypallidal neurons. Classic BG models suggest that all GP neurons receive GABAergic inputs from striato-pallidal indirect spiny projection neurons and glutamatergic inputs from subthalamic neurons. However, whether this synaptic connectivity scheme applies to both GP cell-types is currently unknown. Here, we optogenetically dissect the input organization of prototypic and arkypallidal neurons and further define the circuit mechanism underlying action inhibition in BG. Our results highlight that an increased activity of arkypallidal neurons is required to inhibit locomotion. Finally, this work supports the view that arkypallidal neurons are part of a novel disynaptic feedback loop that broadcast inhibitory control on movement execution.; 17 18 Keywords: external globus pallidus, prototypic and arkypallidal neurons, optogenetic manipulation, 19 indirect pathway, subthalamic nucleus, disynaptic loop, inhibitory locomotion control 20 21 22 23 24 25 26 Highlights: 27-Striatopallidal and subthalamic nucleus inputs are differentially integrated by prototypic and 28 arkypallidal GP neurons 29-The axon collaterals of prototypic neurons powerfully regulate the activity of arkypallidal neurons 30 and form a novel disynaptic microcircuit motif within the GP 31-Striatopallidal inputs can gate the synaptic integration of subthalamic inputs by arkypallidal neurons 32-Disynaptic activation of arkypallidal neurons represents a novel basal ganglia network mechanism 33 supporting global motor suppression 34 35
Databáze: OpenAIRE
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