Key modulatory role of presynaptic adenosine A2A receptors in cortical neurotransmission to the striatal direct pathway

César Quiroz, Rafael Luján, Motokazu Uchigashima, Ana Patrícia Simoes, Talia N. Lerner, Janusz Borycz, Anil Kachroo, Paula M. Canas, Marco Orru, Michael A. Schwarzschild, Diane L. Rosin, Anatol C. Kreitzer, Rodrigo A. Cunha, Masahiko Watanabe, Sergi Ferré*

*Corresponding author for this work

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D 1 and D2 receptors, respectively. Adenosine A2A receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A 2A receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2A receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)1321-1344
Number of pages24
JournalTheScientificWorldJournal
Volume9
DOIs
StatePublished - Nov 18 2009

Keywords

  • Adenosine A receptor
  • Basal ganglia
  • Glutamatergic neurotransmission
  • Medium spiny neuron
  • Presynaptic receptors
  • Striatum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)

Fingerprint Dive into the research topics of 'Key modulatory role of presynaptic adenosine A<sub>2A</sub> receptors in cortical neurotransmission to the striatal direct pathway'. Together they form a unique fingerprint.

  • Cite this

    Quiroz, C., Luján, R., Uchigashima, M., Simoes, A. P., Lerner, T. N., Borycz, J., Kachroo, A., Canas, P. M., Orru, M., Schwarzschild, M. A., Rosin, D. L., Kreitzer, A. C., Cunha, R. A., Watanabe, M., & Ferré, S. (2009). Key modulatory role of presynaptic adenosine A2A receptors in cortical neurotransmission to the striatal direct pathway. TheScientificWorldJournal, 9, 1321-1344. https://doi.org/10.1100/tsw.2009.143