Key modulatory role of presynaptic adenosine A2A receptors in cortical neurotransmission to the striatal direct pathway.
Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1 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 A2A 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.
Quiroz
César
C
National Institute on Drug Abuse, IRP, NIH, DHHS, Baltimore, MD, USA.
Luján
Rafael
R
Uchigashima
Motokazu
M
Simoes
Ana Patrícia
AP
Lerner
Talia N
TN
Borycz
Janusz
J
Kachroo
Anil
A
Canas
Paula M
PM
Orru
Marco
M
Schwarzschild
Michael A
MA
Rosin
Diane L
DL
Kreitzer
Anatol C
AC
Cunha
Rodrigo A
RA
Watanabe
Masahiko
M
Ferré
Sergi
S
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology* / Q000648:ultrastructure; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D017729:Presynaptic Terminals; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000276:immunology / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013574:Synaptosomes / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D001552:Benzazepines; C113602:MSX 3 compound; D043705:Receptor, Adenosine A2A; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D014970:Xanthines; D018698:Glutamic Acid; D048052:Mitogen-Activated Protein Kinase 3