Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output

Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mic...

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Main Authors: Schiemann, Julia, Puggioni, Paolo, Dacre, Joshua, Pelko, Miha, Domanski, Aleksander, van Rossum, Mark C.W., Duguid, Ian
Format: Article
Published: Elsevier 2015
Online Access:https://eprints.nottingham.ac.uk/49633/
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author Schiemann, Julia
Puggioni, Paolo
Dacre, Joshua
Pelko, Miha
Domanski, Aleksander
van Rossum, Mark C.W.
Duguid, Ian
author_facet Schiemann, Julia
Puggioni, Paolo
Dacre, Joshua
Pelko, Miha
Domanski, Aleksander
van Rossum, Mark C.W.
Duguid, Ian
author_sort Schiemann, Julia
building Nottingham Research Data Repository
collection Online Access
description Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior.
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spelling nottingham-496332020-05-04T17:08:04Z https://eprints.nottingham.ac.uk/49633/ Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output Schiemann, Julia Puggioni, Paolo Dacre, Joshua Pelko, Miha Domanski, Aleksander van Rossum, Mark C.W. Duguid, Ian Neuronal activity in primary motor cortex (M1) correlates with behavioral state, but the cellular mechanisms underpinning behavioral state-dependent modulation of M1 output remain largely unresolved. Here, we performed in vivo patch-clamp recordings from layer 5B (L5B) pyramidal neurons in awake mice during quiet wakefulness and self-paced, voluntary movement. We show that L5B output neurons display bidirectional (i.e., enhanced or suppressed) firing rate changes during movement, mediated via two opposing subthreshold mechanisms: (1) a global decrease in membrane potential variability that reduced L5B firing rates (L5Bsuppressed neurons), and (2) a coincident noradrenaline-mediated increase in excitatory drive to a subpopulation of L5B neurons (L5Benhanced neurons) that elevated firing rates. Blocking noradrenergic receptors in forelimb M1 abolished the bidirectional modulation of M1 output during movement and selectively impaired contralateral forelimb motor coordination. Together, our results provide a mechanism for how noradrenergic neuromodulation and network-driven input changes bidirectionally modulate M1 output during motor behavior. Elsevier 2015-05-26 Article PeerReviewed Schiemann, Julia, Puggioni, Paolo, Dacre, Joshua, Pelko, Miha, Domanski, Aleksander, van Rossum, Mark C.W. and Duguid, Ian (2015) Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output. Cell Reports, 11 (8). pp. 1319-1330. ISSN 2211-1247 https://www.sciencedirect.com/science/article/pii/S221112471500443X?via%3Dihub doi:10.1016/j.celrep.2015.04.042 doi:10.1016/j.celrep.2015.04.042
spellingShingle Schiemann, Julia
Puggioni, Paolo
Dacre, Joshua
Pelko, Miha
Domanski, Aleksander
van Rossum, Mark C.W.
Duguid, Ian
Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output
title Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output
title_full Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output
title_fullStr Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output
title_full_unstemmed Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output
title_short Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output
title_sort cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output
url https://eprints.nottingham.ac.uk/49633/
https://eprints.nottingham.ac.uk/49633/
https://eprints.nottingham.ac.uk/49633/