Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.
Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.
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DOI：
10.1371/journal.pone.0095090
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang CT
中科院分区：
文献类型：
--
作者：
Huang PC;Hsiao YT;Kao SY;Chen CF;Chen YC;Chiang CW;Lee CF;Lu JC;Chern Y;Wang CT
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 A2A receptor (A2AR) regulates retinal waves and whether A2AR regulation of retinal waves acts via presynaptic SACs. We showed that A2AR was expressed in the inner plexiform layer and ganglion cell layer of the developing rat retina. Knockdown of A2AR decreased the frequency of spontaneous Ca2+ transients, suggesting that endogenous A2AR may up-regulate wave frequency. To investigate whether A2AR 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 A2AR (A2AR-WT) in SACs, suggesting that A2AR may up-regulate retinal waves via presynaptic SACs. Subsequent patch-clamp recordings on RGCs revealed that presynaptic A2AR-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 A2AR may not affect the membrane properties of postsynaptic RGCs. In contrast, by expressing the C-terminal truncated A2AR mutant (A2AR-ΔC) in SACs, the wave frequency was reduced compared to the A2AR-WT, but was similar to the control, suggesting that the full-length A2AR in SACs is required for A2AR up-regulation of retinal waves. A2AR up-regulates the frequency of retinal waves via presynaptic SACs, requiring its full-length protein structure. Thus, by coupling with the downstream intracellular signaling, A2AR may have a great capacity to modulate patterned spontaneous activity during neural circuit refinement.
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影响因子：
56.9
作者：
Penn, AA;Riquelme, PA;Shatz, CJ
通讯作者：
Shatz, CJ
影响因子：
3.7
作者：
Chiang, Chung-Wei;Chen, Yu-Chieh;Wang, Chih-Tien
通讯作者：
Wang, Chih-Tien
DOI：
10.1523/jneurosci.5309-12.2012
发表时间：
2012-01-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ford KJ;Félix AL;Feller MB
通讯作者：
Feller MB
DOI：
10.1007/978-1-61779-160-4_16
发表时间：
2011-01-01
期刊：
SIGNAL TRANSDUCTION PROTOCOLS, THIRD EDITION
影响因子：
--
作者：
Depry, Charlene;Zhang, Jin
通讯作者：
Zhang, Jin
DOI：
10.1073/pnas.0600137103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Saucerman, Jeffrey J.;Zhang, Jin;McCulloch, Andrew D.
通讯作者：
McCulloch, Andrew D.