4.8 Article

Distinct Developmental Origins Manifest in the Specialized Encoding of Movement by Adult Neurons of the External Globus Pallidus

Journal

NEURON
Volume 86, Issue 2, Pages 501-513

Publisher

CELL PRESS
DOI: 10.1016/j.neuron.2015.03.007

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Funding

  1. Medical Research Council UK (MRC) [UU138197109, MC_UU_12020/5]
  2. Monument Trust Discovery Award from Parkinson's UK [J-0901]
  3. Wellcome Trust [101821, 086602]
  4. MRC [MR/K004387/1]
  5. University of Oxford Clarendon Fund Scholarship
  6. European Research Council under European Community [207807]
  7. Human Frontier Science Program [CDA0023/2008-C]
  8. MRC [G0501173, MC_UU_12024/5, MC_UU_12024/2, MC_U138197109, MC_UU_12020/5] Funding Source: UKRI
  9. Medical Research Council [MC_UU_12024/2, MC_UU_12024/5, MC_UU_12020/5, MC_U138197109, G0501173, MR/K004387/1] Funding Source: researchfish
  10. Parkinson's UK [J-0901] Funding Source: researchfish
  11. Wellcome Trust [101821/Z/13/Z] Funding Source: researchfish
  12. Wellcome Trust [101821/Z/13/Z] Funding Source: Wellcome Trust

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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 twoGABAergicGPecell 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.

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