Dopamine Receptor-Expressing Neurons Are Differently Distributed throughout Layers of the Motor Cortex to Control Dexterity.

Przemyslaw E Cieslak, Sylwia Drabik, Anna Gugula, Aleksandra Trenk, Martyna Gorkowska, Kinga Przybylska, Lukasz Szumiec, Grzegorz Kreiner, Jan Rodriguez Parkitna, Anna Blasiak
Author Information
  1. Przemyslaw E Cieslak: Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow 30-387, Poland pe.cieslak@uj.edu.pl anna.blasiak@uj.edu.pl.
  2. Sylwia Drabik: Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow 30-387, Poland.
  3. Anna Gugula: Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow 30-387, Poland. ORCID
  4. Aleksandra Trenk: Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow 30-387, Poland. ORCID
  5. Martyna Gorkowska: Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow 30-387, Poland.
  6. Kinga Przybylska: Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow 30-387, Poland.
  7. Lukasz Szumiec: Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow 31-343, Poland.
  8. Grzegorz Kreiner: Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow 31-343, Poland.
  9. Jan Rodriguez Parkitna: Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow 31-343, Poland. ORCID
  10. Anna Blasiak: Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow 30-387, Poland pe.cieslak@uj.edu.pl anna.blasiak@uj.edu.pl. ORCID

Abstract

The motor cortex comprises the primary descending circuits for flexible control of voluntary movements and is critically involved in motor skill learning. Motor skill learning is impaired in patients with Parkinson's disease, but the precise mechanisms of motor control and skill learning are still not well understood. Here we have used transgenic mice, electrophysiology, in situ hybridization, and neural tract-tracing methods to target genetically defined cell types expressing D1 and D2 dopamine receptors in the motor cortex. We observed that putative D1 and D2 dopamine receptor-expressing neurons (D1+ and D2+, respectively) are organized in highly segregated, nonoverlapping populations. Moreover, based on ex vivo patch-clamp recordings, we showed that D1+ and D2+ cells have distinct morphological and electrophysiological properties. Finally, we observed that chemogenetic inhibition of D2+, but not D1+, neurons disrupts skilled forelimb reaching in adult mice. Overall, these results demonstrate that dopamine receptor-expressing cells in the motor cortex are highly segregated and play a specialized role in manual dexterity.

Keywords

References

  1. Nat Neurosci. 2010 Jan;13(1):133-40 [PMID: 20023653]
  2. Science. 2000 Oct 20;290(5491):533-6 [PMID: 11039938]
  3. Nat Commun. 2017 Jun 09;8:15834 [PMID: 28598433]
  4. Stroke. 2002 Jul;33(7):1869-75 [PMID: 12105368]
  5. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76 [PMID: 18344392]
  6. Elife. 2022 May 04;11: [PMID: 35506662]
  7. BMC Bioinformatics. 2021 Apr 26;22(1):214 [PMID: 33902456]
  8. J Neurosci. 2007 Sep 12;27(37):9817-23 [PMID: 17855595]
  9. Mov Disord. 2021 Jul;36(7):1565-1577 [PMID: 33606292]
  10. Nat Methods. 2012 Jul;9(7):671-5 [PMID: 22930834]
  11. Science. 1990 Dec 7;250(4986):1429-32 [PMID: 2147780]
  12. Trends Neurosci. 1989 Oct;12(10):366-75 [PMID: 2479133]
  13. Brain Behav. 2018 Nov;8(11):e01132 [PMID: 30264518]
  14. Nat Neurosci. 2015 Sep;18(9):1299-1309 [PMID: 26237365]
  15. Front Neural Circuits. 2014 Feb 28;8:13 [PMID: 24616667]
  16. Neurobiol Dis. 2021 Jan;147:105159 [PMID: 33152506]
  17. J Clin Invest. 2017 Feb 1;127(2):720-734 [PMID: 28112685]
  18. PLoS Biol. 2011 Jan 04;9(1):e1000572 [PMID: 21245906]
  19. J Hand Ther. 2013 Apr-Jun;26(2):148-54; quiz 155 [PMID: 23231827]
  20. Nature. 2010 Jul 29;466(7306):622-6 [PMID: 20613723]
  21. J Physiol. 2021 Jan;599(1):231-252 [PMID: 32997815]
  22. Neuropsychopharmacology. 2011 Sep;36(10):2097-102 [PMID: 21697824]
  23. J Neurosci. 2017 Jun 14;37(24):5846-5860 [PMID: 28522735]
  24. Cell Rep. 2022 May 10;39(6):110801 [PMID: 35545038]
  25. Front Syst Neurosci. 2011 Jun 08;5:32 [PMID: 21713123]
  26. Trends Neurosci. 1990 Jul;13(7):281-5 [PMID: 1695404]
  27. J Neurosci. 2014 Jun 25;34(26):8894-903 [PMID: 24966388]
  28. Front Neurol. 2014 May 16;5:75 [PMID: 24904519]
  29. J Neurosci. 2012 Aug 1;32(31):10516-21 [PMID: 22855801]
  30. Neuron. 2020 Sep 9;107(5):954-971.e9 [PMID: 32589878]
  31. Nat Neurosci. 2008 Mar;11(3):360-6 [PMID: 18246064]
  32. Sci Adv. 2022 Mar 11;8(10):eabj5167 [PMID: 35263129]
  33. N Engl J Med. 1988 Apr 7;318(14):876-80 [PMID: 3352672]
  34. eNeuro. 2021 Oct 18;8(5): [PMID: 34556558]
  35. Nature. 2014 Jun 12;510(7504):263-7 [PMID: 24805237]
  36. PLoS One. 2009 Sep 17;4(9):e7082 [PMID: 19759902]
  37. Brain Res. 2008 May 1;1207:102-10 [PMID: 18377879]
  38. Klin Wochenschr. 1960 Dec 15;38:1236-9 [PMID: 13726012]
  39. Neuron. 2019 Mar 20;101(6):1042-1056 [PMID: 30897356]
  40. Elife. 2015 Dec 02;4:e10774 [PMID: 26633811]
  41. Nat Protoc. 2008;3(5):866-76 [PMID: 18451794]
  42. Eur J Neurol. 2003 Sep;10(5):567-72 [PMID: 12940840]
  43. Mov Disord. 2006 Oct;21(10):1693-702 [PMID: 16817194]
  44. Nature. 2021 Oct;598(7879):159-166 [PMID: 34616071]
  45. Nature. 2009 Dec 17;462(7275):915-9 [PMID: 19946267]
  46. Front Neurosci. 2009 Dec 15;3(3):337-43 [PMID: 20198150]
  47. Annu Rev Neurosci. 2012;35:559-78 [PMID: 22524789]
  48. J Neurosci. 2008 May 28;28(22):5686-90 [PMID: 18509029]
  49. J Neurosci. 2005 Jun 15;25(24):5700-9 [PMID: 15958736]
  50. Nat Neurosci. 2018 Sep;21(9):1281-1289 [PMID: 30127430]
  51. Addict Biol. 2018 Mar;23(2):569-584 [PMID: 28436559]
  52. PLoS One. 2015 May 04;10(5):e0124986 [PMID: 25938462]
  53. J Neurosci. 2011 Feb 16;31(7):2481-7 [PMID: 21325515]
  54. Cell Rep. 2018 Mar 6;22(10):2767-2783 [PMID: 29514103]
  55. Bioinformatics. 2011 Sep 1;27(17):2453-4 [PMID: 21727141]
  56. Nature. 2021 Oct;598(7879):86-102 [PMID: 34616075]
  57. Front Cell Neurosci. 2022 Feb 25;16:836116 [PMID: 35281300]
  58. Nat Neurosci. 2010 Jun;13(6):739-44 [PMID: 20436481]
  59. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):5093-8 [PMID: 15051874]
  60. Neuron. 2016 Feb 17;89(4):683-94 [PMID: 26889809]
  61. BMC Neurosci. 2007 Jan 03;8:4 [PMID: 17201924]
  62. J Parkinsons Dis. 2022;12(4):1083-1113 [PMID: 35253780]
  63. J Neurosci. 2012 Apr 4;32(14):4959-71 [PMID: 22492051]
  64. Nat Neurosci. 1998 Jul;1(3):230-4 [PMID: 10195148]
  65. Front Neuroanat. 2010 Oct 07;4: [PMID: 20953289]

MeSH Term

Mice
Humans
Animals
Motor Cortex
Receptors, Dopamine D1
Dopaminergic Neurons
Mice, Transgenic
Brain
Corpus Striatum

Chemicals

Receptors, Dopamine D1

Word Cloud

Created with Highcharts 10.0.0motorcortexskilllearningdopamineD1+D2+controlMotormiceD1D2observedreceptor-expressingneuronshighlysegregatedcellscomprisesprimarydescendingcircuitsflexiblevoluntarymovementscriticallyinvolvedimpairedpatientsParkinson'sdiseaseprecisemechanismsstillwellunderstoodusedtransgenicelectrophysiologysituhybridizationneuraltract-tracingmethodstargetgeneticallydefinedcelltypesexpressingreceptorsputativerespectivelyorganizednonoverlappingpopulationsMoreoverbasedexvivopatch-clamprecordingsshoweddistinctmorphologicalelectrophysiologicalpropertiesFinallychemogeneticinhibitiondisruptsskilledforelimbreachingadultOverallresultsdemonstrateplayspecializedrolemanualdexterityDopamineReceptor-ExpressingNeuronsDifferentlyDistributedthroughoutLayersCortexControlDexterity

Similar Articles

Cited By