Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex

The primary motor cortex (MOp) is an important site for motor skill learning. Interestingly, neurons in MOp possess reward-related activity, presumably to facilitate reward-based motor learning. While pyramidal neurons (PNs) and different subtypes of GABAergic inhibitory interneurons (INs) in MOp al...

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Main Authors: Candice Lee, Sandrine L. Côté, Nima Raman, Hritvic Chaudhary, Bryan C. Mercado, Simon X. Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Neural Circuits
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncir.2023.1093066/full
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author Candice Lee
Sandrine L. Côté
Nima Raman
Hritvic Chaudhary
Bryan C. Mercado
Simon X. Chen
Simon X. Chen
Simon X. Chen
author_facet Candice Lee
Sandrine L. Côté
Nima Raman
Hritvic Chaudhary
Bryan C. Mercado
Simon X. Chen
Simon X. Chen
Simon X. Chen
author_sort Candice Lee
collection DOAJ
description The primary motor cortex (MOp) is an important site for motor skill learning. Interestingly, neurons in MOp possess reward-related activity, presumably to facilitate reward-based motor learning. While pyramidal neurons (PNs) and different subtypes of GABAergic inhibitory interneurons (INs) in MOp all undergo cell-type specific plastic changes during motor learning, the vasoactive intestinal peptide-expressing inhibitory interneurons (VIP-INs) in MOp have been shown to preferentially respond to reward and play a critical role in the early phases of motor learning by triggering local circuit plasticity. To understand how VIP-INs might integrate various streams of information, such as sensory, pre-motor, and reward-related inputs, to regulate local plasticity in MOp, we performed monosynaptic rabies tracing experiments and employed an automated cell counting pipeline to generate a comprehensive map of brain-wide inputs to VIP-INs in MOp. We then compared this input profile to the brain-wide inputs to somatostatin-expressing inhibitory interneurons (SST-INs) and parvalbumin-expressing inhibitory interneurons (PV-INs) in MOp. We found that while all cell types received major inputs from sensory, motor, and prefrontal cortical regions, as well as from various thalamic nuclei, VIP-INs received more inputs from the orbital frontal cortex (ORB) – a region associated with reinforcement learning and value predictions. Our findings provide insight on how the brain leverages microcircuit motifs by both integrating and partitioning different streams of long-range input to modulate local circuit activity and plasticity.
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spelling doaj.art-eb4eaf76f2a94efbaed2cae2f28191512023-05-19T16:03:36ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102023-05-011710.3389/fncir.2023.10930661093066Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortexCandice Lee0Sandrine L. Côté1Nima Raman2Hritvic Chaudhary3Bryan C. Mercado4Simon X. Chen5Simon X. Chen6Simon X. Chen7Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, CanadaDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, CanadaDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, CanadaDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, CanadaDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, CanadaDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, CanadaBrain and Mind Research Institute, University of Ottawa, Ottawa, ON, CanadaCenter for Neural Dynamics, University of Ottawa, Ottawa, ON, CanadaThe primary motor cortex (MOp) is an important site for motor skill learning. Interestingly, neurons in MOp possess reward-related activity, presumably to facilitate reward-based motor learning. While pyramidal neurons (PNs) and different subtypes of GABAergic inhibitory interneurons (INs) in MOp all undergo cell-type specific plastic changes during motor learning, the vasoactive intestinal peptide-expressing inhibitory interneurons (VIP-INs) in MOp have been shown to preferentially respond to reward and play a critical role in the early phases of motor learning by triggering local circuit plasticity. To understand how VIP-INs might integrate various streams of information, such as sensory, pre-motor, and reward-related inputs, to regulate local plasticity in MOp, we performed monosynaptic rabies tracing experiments and employed an automated cell counting pipeline to generate a comprehensive map of brain-wide inputs to VIP-INs in MOp. We then compared this input profile to the brain-wide inputs to somatostatin-expressing inhibitory interneurons (SST-INs) and parvalbumin-expressing inhibitory interneurons (PV-INs) in MOp. We found that while all cell types received major inputs from sensory, motor, and prefrontal cortical regions, as well as from various thalamic nuclei, VIP-INs received more inputs from the orbital frontal cortex (ORB) – a region associated with reinforcement learning and value predictions. Our findings provide insight on how the brain leverages microcircuit motifs by both integrating and partitioning different streams of long-range input to modulate local circuit activity and plasticity.https://www.frontiersin.org/articles/10.3389/fncir.2023.1093066/fullmonosynaptic circuit tracinginhibitory neuronsmotor cortexassociative learningorbital frontal cortex (ORB)
spellingShingle Candice Lee
Sandrine L. Côté
Nima Raman
Hritvic Chaudhary
Bryan C. Mercado
Simon X. Chen
Simon X. Chen
Simon X. Chen
Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex
Frontiers in Neural Circuits
monosynaptic circuit tracing
inhibitory neurons
motor cortex
associative learning
orbital frontal cortex (ORB)
title Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex
title_full Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex
title_fullStr Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex
title_full_unstemmed Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex
title_short Whole-brain mapping of long-range inputs to the VIP-expressing inhibitory neurons in the primary motor cortex
title_sort whole brain mapping of long range inputs to the vip expressing inhibitory neurons in the primary motor cortex
topic monosynaptic circuit tracing
inhibitory neurons
motor cortex
associative learning
orbital frontal cortex (ORB)
url https://www.frontiersin.org/articles/10.3389/fncir.2023.1093066/full
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