A comparative study on electrically evoked responses of retinal ganglion cells in distinct retinal areas by computational model

Author(s):  
Shirong Qiu ◽  
Xinxin Li ◽  
Xue Li ◽  
Liming Li
2007 ◽  
Vol 98 (1) ◽  
pp. 122-130 ◽  
Author(s):  
Eric C. Gustafson ◽  
Eric R. Stevens ◽  
Herman Wolosker ◽  
Robert F. Miller

We have combined electrophysiology and chemical separation and measurement techniques with capillary electrophoresis (CE) to evaluate the role of endogenous d-serine as an NMDA receptor (NMDAR) coagonist in the salamander retina. Electrophysiological experiments were carried out using whole cell recordings from retinal ganglion cells and extracellular recordings of the proximal negative response (PNR), while bath applying two d-serine degrading enzymes, including d-amino acid oxidase (DAAO) and d-serine deaminase (DsdA). The addition of either enzyme resulted in a significant and rapid decline in the light-evoked responses observed in ganglion cell and PNR recordings. The addition of exogenous d-serine in the presence of the enzymes restored the light-evoked responses to the control or supracontrol amplitudes. Heat-inactivated enzymes had no effect on the light responses and blocking NMDARs with AP7 eliminated the suppressive influence of the enzymes as well as the response enhancement normally associated with exogenous d-serine application. CE was used to separate amino acid racemates and to study the selectivity of DAAO and DsdA against d-serine and glycine. Both enzymes showed high selectivity for d-serine without significant effects on glycine. Our results strongly support the concept that endogenous d-serine plays an essential role as a coagonist for NMDARs, allowing them to contribute to the light-evoked responses of retinal ganglion cells. Furthermore under our experimental conditions, these coagonist sites are not saturated so that modulation of NMDAR sensitivity can be achieved with further modulaton of d-serine.


2007 ◽  
Vol 7 (14) ◽  
pp. 7 ◽  
Author(s):  
Guo-Yong Wang ◽  
Deborah A. van der List ◽  
Joseph P. Nemargut ◽  
Julie L. Coombs ◽  
Leo M. Chalupa

1997 ◽  
Vol 77 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Peter D. Lukasiewicz ◽  
James A. Wilson ◽  
Jean E. Lawrence

Lukasiewicz, Peter D., James A. Wilson, and Jean E. Lawrence. AMPA-preferring receptors mediate excitatory synaptic inputs to retinal ganglion cells. J. Neurophysiol. 77: 57–64, 1997. Pharmacological studies were performed to determine whether α-amino-3-hydroxy-5-methyl-4-isoazoleprionic acid (AMPA)- and/or kainate (KA)-preferring receptors mediate excitatory synaptic inputs to tiger salamander retinal ganglion cells. Excitatory postsynaptic currents (EPSCs), evoked either by light or by stimulating bipolar cells with puffs of K+, were measured using whole cell recording techniques in the tiger salamander retinal slice. The AMPA/KA component of the EPSCs was isolated by including antagonists of glycine-, γ-aminobutyric acid (GABA)- and NMDA-receptors in the bath. The AMPA-preferring receptor antagonists, 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI-52466) and 1-(4-aminophenyl)-3-methylcarbamyl - 4 - methyl - 7,8 - methylenedioxy - 3,4 - dihydro - 5H - 2,3 - benzodiazepine (GYKI-53665), reduced light-evoked EPSCs and K+ puff-evoked EPSCs amplitudes in a concentration-dependent manner. The IC50 values for GYKI-52466 were 3.6 and 4.2 μM for the light- and puff-evoked responses, respectively. The more potent GYKI-53665 had IC50 values of 0.7 μM for both the light- and puff evoked responses. KA activates both KA- and AMPA-preferring receptors. KA-evoked currents were completely blocked by 10–40 μM GYKI-53665, indicating that little or no excitatory synaptic current was mediated by KA-preferring receptors. Concanavalin A, a compound that preferentially potentiates responses mediated by KA-preferring receptors, did not enhance either EPSCs or glutamate-evoked responses. By contrast, cyclothiazide, which selectively enhances AMPA-preferring receptor mediated responses, was found to enhance both EPSCs and glutamate-evoked currents. Our results indicate that the non-NMDA component of ganglion cell EPSCs is mediated by AMPA-preferring receptors and not significantly by KA-preferring receptors.


Sign in / Sign up

Export Citation Format

Share Document