Journal
THESCIENTIFICWORLDJOURNAL
Volume 9, Issue -, Pages 1321-1344Publisher
HINDAWI LTD
DOI: 10.1100/tsw.2009.143
Keywords
adenosine A(2A) receptor; striatum; basal ganglia; medium spiny neuron; glutamatergic neurotransmission; presynaptic receptors
Categories
Funding
- National Institute on Drug Abuse
- CHDI Foundation
- Consejeria de Educacion y Ciencia de la Junta de Comunidades de Castilla-La Mancha [PAI08-0174-6967]
- Fundacao para a Ciencia e Tecnologia [FCT-PTDC/SAU-NEU/81064/2006]
- National Institutes of Health [RO1 NS054978]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [K24NS060991, R01NS054978] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [ZIADA000493] Funding Source: NIH RePORTER
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Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D-1 and D-2 receptors, respectively. Adenosine A(2A) receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D-2 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 A(2A) 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 A(2A) receptors could provide a new target for the treatment of neuropsychiatric disorders.
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