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• W2100698933 abstract "Glutamate release at bipolar to ganglion cell synapses activates NMDA and AMPA/kainic acid (KA) ionotropic glutamate receptors. Their relative strength determines the output signals of the retina. We found that this balance is tightly regulated by presynaptic inhibition that preferentially suppresses NMDA receptor (NMDAR) activation. In transient ON-OFF neurons, block of GABA and glycine feedback enhanced total NMDAR charge by 35-fold in the ON response and 9-fold in the OFF compared with a 1.7-fold enhancement of AMPA/KA receptors. Blocking only glycine receptors enhanced the NMDAR excitatory postsynaptic current 10-fold in the ON and 2-fold in the OFF pathway. Blocking GABA(A) or GABA(C) receptors (GABA(C)Rs or GABA(A)Rs) produced small changes in total NMDAR charge. When both GABA(A)Rs and GABA(C)Rs were blocked, the total NMDAR charge increased ninefold in the ON and fivefold in the OFF pathway. This exposed a strong GABA(C)R feedback to bipolar cells that was suppressed by serial amacrine cell synapses mediated by GABA(A)Rs. The results indicate that NMDAR currents are large but latent, held in check by dual GABA and glycine presynaptic inhibition. One example of this controlled NMDAR activation is the cross talk between ON and OFF pathways. Blocking the ON pathway increased NMDAR relative strength in the OFF pathway. Stimulus prolongation similarly increased the NMDAR relative strength in the OFF response. This NMDAR enhancement was produced by a diminution in GABA and glycine feedback. Thus the retinal network recruits NMDAR pathways through presynaptic disinhibition." @default.
• W2100698933 created "2016-06-24" @default.
• W2100698933 creator A5012714151 @default.
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• W2100698933 date "2014-07-01" @default.
• W2100698933 modified "2023-10-18" @default.
• W2100698933 title "Disinhibitory recruitment of NMDA receptor pathways in retina" @default.
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• W2100698933 doi "https://doi.org/10.1152/jn.00817.2013" @default.
• W2100698933 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4064386" @default.
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