Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.
BACKGROUND: Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs) and retinal ganglion cells (RGCs). The ne...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4002430?pdf=render |
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| author | Pin-Chien Huang Yu-Tien Hsiao Shao-Yen Kao Ching-Feng Chen Yu-Chieh Chen Chung-Wei Chiang Chien-Fei Lee Juu-Chin Lu Yijuang Chern Chih-Tien Wang |
| author_facet | Pin-Chien Huang Yu-Tien Hsiao Shao-Yen Kao Ching-Feng Chen Yu-Chieh Chen Chung-Wei Chiang Chien-Fei Lee Juu-Chin Lu Yijuang Chern Chih-Tien Wang |
| author_sort | Pin-Chien Huang |
| collection | DOAJ |
| description | BACKGROUND: Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs) and retinal ganglion cells (RGCs). The neuromodulator adenosine is essential for the generation of retinal waves. However, the cellular basis underlying adenosine's regulation of retinal waves remains elusive. Here, we investigated whether and how the adenosine A(2A) receptor (A(2A)R) regulates retinal waves and whether A(2A)R regulation of retinal waves acts via presynaptic SACs. METHODOLOGY/PRINCIPAL FINDINGS: We showed that A(2A)R was expressed in the inner plexiform layer and ganglion cell layer of the developing rat retina. Knockdown of A(2A)R decreased the frequency of spontaneous Ca²⁺ transients, suggesting that endogenous A(2A)R may up-regulate wave frequency. To investigate whether A(2A)R acts via presynaptic SACs, we targeted gene expression to SACs by the metabotropic glutamate receptor type II promoter. Ca²⁺ transient frequency was increased by expressing wild-type A(2A)R (A2AR-WT) in SACs, suggesting that A(2A)R may up-regulate retinal waves via presynaptic SACs. Subsequent patch-clamp recordings on RGCs revealed that presynaptic A(2A)R-WT increased the frequency of wave-associated postsynaptic currents (PSCs) or depolarizations compared to the control, without changing the RGC's excitability, membrane potentials, or PSC charge. These findings suggest that presynaptic A(2A)R may not affect the membrane properties of postsynaptic RGCs. In contrast, by expressing the C-terminal truncated A(2A)R mutant (A(2A)R-ΔC) in SACs, the wave frequency was reduced compared to the A(2A)R-WT, but was similar to the control, suggesting that the full-length A(2A)R in SACs is required for A(2A)R up-regulation of retinal waves. CONCLUSIONS/SIGNIFICANCE: A(2A)R up-regulates the frequency of retinal waves via presynaptic SACs, requiring its full-length protein structure. Thus, by coupling with the downstream intracellular signaling, A(2A)R may have a great capacity to modulate patterned spontaneous activity during neural circuit refinement. |
| first_indexed | 2024-12-10T17:26:08Z |
| format | Article |
| id | doaj.art-1baf4449dbd84ea292608f3e71c6aa89 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T17:26:08Z |
| publishDate | 2014-01-01 |
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| spelling | doaj.art-1baf4449dbd84ea292608f3e71c6aa892022-12-22T01:39:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9509010.1371/journal.pone.0095090Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.Pin-Chien HuangYu-Tien HsiaoShao-Yen KaoChing-Feng ChenYu-Chieh ChenChung-Wei ChiangChien-Fei LeeJuu-Chin LuYijuang ChernChih-Tien WangBACKGROUND: Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs) and retinal ganglion cells (RGCs). The neuromodulator adenosine is essential for the generation of retinal waves. However, the cellular basis underlying adenosine's regulation of retinal waves remains elusive. Here, we investigated whether and how the adenosine A(2A) receptor (A(2A)R) regulates retinal waves and whether A(2A)R regulation of retinal waves acts via presynaptic SACs. METHODOLOGY/PRINCIPAL FINDINGS: We showed that A(2A)R was expressed in the inner plexiform layer and ganglion cell layer of the developing rat retina. Knockdown of A(2A)R decreased the frequency of spontaneous Ca²⁺ transients, suggesting that endogenous A(2A)R may up-regulate wave frequency. To investigate whether A(2A)R acts via presynaptic SACs, we targeted gene expression to SACs by the metabotropic glutamate receptor type II promoter. Ca²⁺ transient frequency was increased by expressing wild-type A(2A)R (A2AR-WT) in SACs, suggesting that A(2A)R may up-regulate retinal waves via presynaptic SACs. Subsequent patch-clamp recordings on RGCs revealed that presynaptic A(2A)R-WT increased the frequency of wave-associated postsynaptic currents (PSCs) or depolarizations compared to the control, without changing the RGC's excitability, membrane potentials, or PSC charge. These findings suggest that presynaptic A(2A)R may not affect the membrane properties of postsynaptic RGCs. In contrast, by expressing the C-terminal truncated A(2A)R mutant (A(2A)R-ΔC) in SACs, the wave frequency was reduced compared to the A(2A)R-WT, but was similar to the control, suggesting that the full-length A(2A)R in SACs is required for A(2A)R up-regulation of retinal waves. CONCLUSIONS/SIGNIFICANCE: A(2A)R up-regulates the frequency of retinal waves via presynaptic SACs, requiring its full-length protein structure. Thus, by coupling with the downstream intracellular signaling, A(2A)R may have a great capacity to modulate patterned spontaneous activity during neural circuit refinement.http://europepmc.org/articles/PMC4002430?pdf=render |
| spellingShingle | Pin-Chien Huang Yu-Tien Hsiao Shao-Yen Kao Ching-Feng Chen Yu-Chieh Chen Chung-Wei Chiang Chien-Fei Lee Juu-Chin Lu Yijuang Chern Chih-Tien Wang Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina. PLoS ONE |
| title | Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina. |
| title_full | Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina. |
| title_fullStr | Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina. |
| title_full_unstemmed | Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina. |
| title_short | Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina. |
| title_sort | adenosine a 2a receptor up regulates retinal wave frequency via starburst amacrine cells in the developing rat retina |
| url | http://europepmc.org/articles/PMC4002430?pdf=render |
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