Thalamic input to motor cortex facilitates goal-directed action initiation

• Type of Material: Article
• Authors: Naoya Takahashi, Humboldt-Universität zu Berlin; Sara Moberg, Einstein Center for Neurosciences Berlin; Timothy A Zolnik, Humboldt-Universität zu Berlin; Julien Catanese, Emory University; Robert NS Sachdev, Humboldt-Universität zu Berlin; Matthew E Larkum, Humboldt-Universität zu Berlin; Dieter Jaeger, Emory University
• Language: English
• Date: 2021-09-27
• Publisher: Elsevier Inc
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 The Author(s). Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cub.2021.06.089
• Title of Journal or Parent Work: Current Biology
• Volume: 31
• Issue: 18
• Start Page: 4148
• End Page: 4155.e4
• Grant/Funding Information: This study was supported by the University of Bordeaux (Initiative of Excellence to N.T.), the Region Nouvelle-Aquitaine (to N.T.), the ATIP-Avenir program (to N.T.), the Einstein Center for Neurosciences Berlin (PhD fellowship to S.M.), the Deutsche Forschungsgemeinschaft (Exc 257 NeuroCure, LA 3442/3–1, LA 3442/6–1, project number 327654276 SFB1315 to M.E.L.), the European Union Horizon 2020 Research and Innovation Programme (72070/HBP SGA1, 785907/HBP SGA2, 670118/ERC ActiveCortex to M.E.L.), the Einstein Foundation Berlin (EVF-2017–363 to D.J.), and the NINDS (1UO1NS094302, R01NS111470 to D.J.).
• Keywords: Animals; Axons; Basal Ganglia; goal-directed action; Goals; Thalamus; Motor Cortex; Neural Pathways; axonal calcium imaging; Mice; reaction time; thalamocortical projection; anterior lateral motor cortex; motor thalamus

Abstract

Prompt execution of planned motor action is essential for survival. The interactions between frontal cortical circuits and the basal ganglia are central to goal-oriented action selection and initiation.1–4 In rodents, the ventromedial thalamic nucleus (VM) is one of the critical nodes that conveys the output of the basal ganglia to the frontal cortical areas including the anterior lateral motor cortex (ALM).5–9 Recent studies showed the critical role of ALM and its interplay with the motor thalamus in preparing sensory-cued rewarded movements, specifically licking.10–12 Work in primates suggests that the basal ganglia output to the motor thalamus transmits an urgency or vigor signal,13–15 which leads to shortened reaction times and faster movement initiation. As yet, little is known about what signals are transmitted from the motor thalamus to the cortex during cued movements and how these signals contribute to movement initiation. In the present study, we employed a tactile-cued licking task in mice while monitoring reaction times of the initial lick. We found that inactivation of ALM delayed the initiation of cued licking. Two-photon Ca2+ imaging of VM axons revealed that the majority of the axon terminals in ALM were transiently active during licking. Their activity was predictive of the time of the first lick. Chemogenetic and optogenetic manipulation of VM axons in ALM indicated that VM inputs facilitate the initiation of cue-triggered and impulsive licking in trained mice. Our results suggest that VM thalamocortical inputs increase the probability and vigor of initiating planned motor responses.