A Disynaptic Circuit in the Globus Pallidus Controls Locomotion Inhibition

• Published in: Current biology 2021-02, Vol.31 (4), p.707-721.e7
• Main Authors: Aristieta, Asier, Barresi, Massimo, Azizpour Lindi, Shiva, Barrière, Grégory, Courtand, Gilles, de la Crompe, Brice, Guilhemsang, Lise, Gauthier, Sophie, Fioramonti, Stéphanie, Baufreton, Jérôme, Mallet, Nicolas P.
• Format: Article
• Language: English
• Subjects: Animals; disynaptic loop; external globus pallidus; Female; Globus Pallidus - cytology; indirect pathway; inhibitory locomotion control; Life Sciences; Locomotion - physiology; Male; Mice; Mice, Inbred C57BL; Neural Pathways; Neurobiology; Neurons; Neurons and Cognition; optogenetic manipulation; Optogenetics; prototypic and arkypallidal neurons; subthalamic nucleus; Subthalamic Nucleus - cytology; Synapses
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2020.11.019

The basal ganglia (BG) inhibit movements through two independent circuits: the striatal neuron-indirect and the subthalamic nucleus-hyperdirect pathways. These pathways exert opposite effects onto external globus pallidus (GPe) neurons, whose functional importance as a relay has changed drastically with the discovery of two distinct cell types, namely the prototypic and the arkypallidal neurons. However, little is known about the synaptic connectivity scheme of different GPe neurons toward both motor-suppressing pathways, as well as how opposite changes in GPe neuronal activity relate to locomotion inhibition. Here, we optogenetically dissect the input organizations of prototypic and arkypallidal neurons and further define the circuit mechanism and behavioral outcome associated with activation of the indirect or hyperdirect pathways. This work reveals that arkypallidal neurons are part of a novel disynaptic feedback loop differentially recruited by the indirect or hyperdirect pathways and that broadcasts inhibitory control onto locomotion only when arkypallidal neurons increase their activity. [Display omitted] •STR and STN inputs are differentially integrated by Proto and Arky GPe neurons•Axon collaterals of Proto GPe neurons form a disynaptic circuit motif within the GPe•STR inputs can gate the synaptic integration of STN inputs by Arky GPe neurons•Disynaptic disinhibition of Arky GPe neurons supports global motor suppression Aristieta et al. show that striatal indirect and subthalamic nucleus input organizations present cell-type-specific integration in the external globus pallidus leading to opposite activity patterns between prototypic and arkypallidal neurons and opposite behavioral outcomes on movement inhibition during locomotor activity.