Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine A2 Receptor Antagonists
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Animals
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Basal Ganglia / physiology*
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Benzazepines / pharmacology
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Cerebral Cortex / physiology*
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Corpus Striatum / physiology*
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Corpus Striatum / ultrastructure
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Electric Stimulation
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Excitatory Postsynaptic Potentials
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Glutamic Acid / metabolism
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Immunoenzyme Techniques
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Immunohistochemistry
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Male
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Mice
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Mice, Knockout
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Mice, Transgenic
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Microscopy, Electron
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphorylation
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Presynaptic Terminals
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Rats
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Rats, Sprague-Dawley
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Rats, Wistar
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Receptor, Adenosine A2A / immunology
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Receptor, Adenosine A2A / physiology*
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Receptors, Dopamine D1 / antagonists & inhibitors
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Receptors, Dopamine D2 / physiology
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Synaptic Transmission / physiology*
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Synaptosomes / physiology
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Xanthines / pharmacology
Substances
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Adenosine A2 Receptor Antagonists
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Benzazepines
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MSX 3 compound
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Receptor, Adenosine A2A
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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SCH 23390
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Xanthines
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Glutamic Acid
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Mitogen-Activated Protein Kinase 3