scholarly journals NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells

2014 ◽  
Vol 592 (22) ◽  
pp. 4877-4889 ◽  
Author(s):  
Benjamin K. Stafford ◽  
Michael B. Manookin ◽  
Joshua H. Singer ◽  
Jonathan B. Demb
2019 ◽  
Author(s):  
Asia L. Sladek ◽  
Scott Nawy

AbstractAMPA receptors in the CNS are normally impermeable to Ca2+ but aberrant expression of Ca2+-permeable AMPA receptors (CP-AMPARs) occurs in pathological conditions such as ischemia or epilepsy, or in degenerative diseases such as ALS. Here we show that select populations of retinal ganglion cells (RGCs) similarly express high levels of CP-AMPARs in a mouse model of glaucoma. CP-AMPAR expression increased dramatically in both α On and α transient Off RGCs, and this increase was prevented by genomic editing of the GluA2 Q/R site. α On RGCs with elevated CP-AMPAR levels displayed profound synaptic depression, which was reduced by selectively blocking CP-AMPARs, buffering Ca2+ with BAPTA, or with the CB1 antagonist AM251, suggesting that depression was mediated by a retrograde transmitter which might be triggered by influx of Ca2+ through CP-AMPARs. Thus OHT alters the composition of AMPARs and modulates patterns of synaptic activity in select populations of RGCs.


Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 625
Author(s):  
Yang ◽  
Nguyen ◽  
Lin ◽  
Yarmishyn ◽  
Chen ◽  
...  

The mitochondrial genetic disorder, Leber’s hereditary optic neuropathy (LHON), is caused by a mutation in MT-ND4 gene, encoding NADH dehydrogenase subunit 4. It leads to the progressive death of retinal ganglion cells (RGCs) and causes visual impairment or even blindness. However, the precise mechanisms of LHON disease penetrance and progression are not completely elucidated. Human-induced pluripotent stem cells (hiPSCs) offer unique opportunities to investigate disease-relevant phenotypes and regulatory mechanisms underlying LHON pathogenesis at the cellular level. In this study, we successfully generated RGCs by differentiation of LHON patient-specific hiPSCs. We modified the protocol of differentiation to obtain a more enriched population of single-cell RGCs for LHON study. Based on assessing morphology, expression of specific markers and electrophysiological activity, we found that LHON-specific hiPSC-derived were more defective in comparison with normal wild-type RGCs. Based on our previous study, whereby by using microarray analysis we identified that the components of glutamatergic synapse signaling pathway were significantly downregulated in LHON-specific RGCs, we focused our study on glutamate-associated α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. We found that the protein expression levels of the subunits of the AMPA receptor, GluR1 and GluR2, and their associated scaffold proteins were decreased in LHON-RGCs. By performing the co-immunoprecipitation assay, we found several differences in the efficiencies of interaction between AMPA subunits and scaffold proteins between normal and LHON-specific RGCs.


Author(s):  
Kyril I. Kuznetsov ◽  
Vitaliy Yu. Maslov ◽  
Svetlana A. Fedulova ◽  
Nikolai S. Veselovsky

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