title: Distinct developmental origins manifest in the specialized encoding of movement by adult neurons of the external globus pallidus.
abstract: Transcriptional codes initiated during brain development are ultimately realized in adulthood as distinct cell types performing specialized roles in behavior. Focusing on the mouse external globus pallidus (GPe), we demonstrate that the potential contributions of two GABAergic GPe cell types to voluntary action are fated from early life to be distinct. Prototypic GPe neurons derive from the medial ganglionic eminence of the embryonic subpallium and express the transcription factor Nkx2-1. These neurons fire at high rates during alert rest, and encode movements through heterogeneous firing rate changes, with many neurons decreasing their activity. In contrast, arkypallidal GPe neurons originate from lateral/caudal ganglionic eminences, express the transcription factor FoxP2, fire at low rates during rest, and encode movements with robust increases in firing. We conclude that developmental diversity positions prototypic and arkypallidal neurons to fulfil distinct roles in behavior via their disparate regulation of GABA release onto different basal ganglia targets.
authors.affiliation: Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK; Oxford Parkinson's Disease Centre, University of Oxford, Oxford OX1 3QX, UK. Electronic address: paul.dodson@pharm.ox.ac.uk.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Dodson
authors.affiliation: Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Larvin
authors.affiliation: Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Duffell
authors.affiliation: Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
authors.forename: Farid N
authors.initials: FN
authors.lastname: Garas
authors.affiliation: Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Doig
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Kessaris
authors.affiliation: Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Duguid
authors.affiliation: Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Rafal
authors.initials: R
authors.lastname: Bogacz
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Simon J B
authors.initials: SJ
authors.lastname: Butt
authors.affiliation: Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK; Oxford Parkinson's Disease Centre, University of Oxford, Oxford OX1 3QX, UK. Electronic address: peter.magill@pharm.ox.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Magill
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D019070:Cell Lineage / Q000502:physiology; D004745:Enkephalins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005917:Globus Pallidus / Q000166:cytology* / Q000196:embryology / Q000254:growth & development*; D051379:Mice; D009068:Movement / Q000502:physiology*; D009474:Neurons / Q000145:classification* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012372:ROC Curve; D012097:Repressor Proteins / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D004745:Enkephalins; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D011498:Protein Precursors; D012097:Repressor Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid; C033660:preproenkephalin
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