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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2009-01-01
|
| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2009.143 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850169994299572224 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | César Quiroz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ad275f79176c452d8034ffe263f2ceba |
| institution | OA Journals |
| issn | 1537-744X |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-ad275f79176c452d8034ffe263f2ceba2025-08-20T02:20:36ZengWileyThe Scientific World Journal1537-744X2009-01-0191321134410.1100/tsw.2009.143Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct PathwayCésar Quiroz0Rafael Luján1Motokazu Uchigashima2Ana Patrícia Simoes3Talia N. Lerner4Janusz Borycz5Anil Kachroo6Paula M. Canas7Marco Orru8Michael A. Schwarzschild9Diane L. Rosin10Anatol C. Kreitzer11Rodrigo A. Cunha12Masahiko Watanabe13Sergi Ferré14National Institute on Drug Abuse, IR , NIH, DHHS, Baltimore, MD, USADepartamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, SpainDepartment of Anatomy, Hokkaido University School of Medicine, Sapporo, JapanInstitute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, PortugalGladstone Institute of Neurological Disease, Department of Physiology, University of California, San Francisco, USANational Institute on Drug Abuse, IR , NIH, DHHS, Baltimore, MD, USADepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, USAInstitute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, PortugalNational Institute on Drug Abuse, IR , NIH, DHHS, Baltimore, MD, USADepartment of Neurology, MassGeneral Institute for Neurodegenerative Disease, Charlestown, USADepartment of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, USAGladstone Institute of Neurological Disease, Department of Physiology, University of California, San Francisco, USAInstitute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, PortugalDepartment of Anatomy, Hokkaido University School of Medicine, Sapporo, JapanNational Institute on Drug Abuse, IR , NIH, DHHS, Baltimore, MD, USABasal 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.http://dx.doi.org/10.1100/tsw.2009.143 |
| spellingShingle | 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 Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway The Scientific World Journal |
| title | Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway |
| title_full | Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway |
| title_fullStr | Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway |
| title_full_unstemmed | Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway |
| title_short | Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway |
| title_sort | key modulatory role of presynaptic adenosine a2a receptors in cortical neurotransmission to the striatal direct pathway |
| url | http://dx.doi.org/10.1100/tsw.2009.143 |
| work_keys_str_mv | AT cesarquiroz keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT rafaellujan keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT motokazuuchigashima keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT anapatriciasimoes keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT talianlerner keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT januszborycz keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT anilkachroo keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT paulamcanas keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT marcoorru keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT michaelaschwarzschild keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT dianelrosin keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT anatolckreitzer keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT rodrigoacunha keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT masahikowatanabe keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway AT sergiferre keymodulatoryroleofpresynapticadenosinea2areceptorsincorticalneurotransmissiontothestriataldirectpathway |