title: Cellular mechanisms underlying behavioral state-dependent bidirectional modulation of motor cortex output.
abstract: 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.
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Schiemann
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK; Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK; Neuroinformatics Doctoral Training Centre, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Puggioni
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Joshua
authors.initials: J
authors.lastname: Dacre
authors.affiliation: Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK; Neuroinformatics Doctoral Training Centre, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK.
authors.forename: Miha
authors.initials: M
authors.lastname: Pelko
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Domanski
authors.affiliation: Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, UK.
authors.forename: Mark C W
authors.initials: MC
authors.lastname: van Rossum
authors.affiliation: Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK. Electronic address: ian.duguid@ed.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Duguid
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*