title: Nitric oxide mediates activity-dependent plasticity of retinal bipolar cell output via S-nitrosylation.
abstract: Coding a wide range of light intensities in natural scenes poses a challenge for the retina: adaptation to bright light should not compromise sensitivity to dim light. Here we report a novel form of activity-dependent synaptic plasticity, specifically, a "weighted potentiation" that selectively increases output of Mb-type bipolar cells in the goldfish retina in response to weak inputs but leaves the input-output ratio for strong stimuli unaffected. In retinal slice preparation, strong depolarization of bipolar terminals significantly lowered the threshold for calcium spike initiation, which originated from a shift in activation of voltage-gated calcium currents (ICa) to more negative potentials. The process depended upon glutamate-evoked retrograde nitric oxide (NO) signaling as it was eliminated by pretreatment with an NO synthase blocker, TRIM. The NO-dependent ICa modulation was cGMP independent but could be blocked by N-ethylmaleimide (NEM), indicating that NO acted via an S-nitrosylation mechanism. Importantly, the NO action resulted in a weighted potentiation of Mb output in response to small (≤-30 mV) depolarizations. Coincidentally, light flashes with intensity ≥ 2.4 × 10(8) photons/cm(2)/s lowered the latency of scotopic (≤ 2.4 × 10(8) photons/cm(2)/s) light-evoked calcium spikes in Mb axon terminals in an NEM-sensitive manner, but light responses above cone threshold (≥ 3.5 × 10(9) photons/cm(2)/s) were unaltered. Under bright scotopic/mesopic conditions, this novel form of Mb output potentiation selectively amplifies dim retinal inputs at Mb → ganglion cell synapses. We propose that this process might counteract decreases in retinal sensitivity during light adaptation by preventing the loss of visual information carried by dim scotopic signals.
authors.affiliation: Department of Biomedical Sciences and Department of Chemistry, Colorado State University, Ft. Collins, Colorado 80523.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Tooker
authors.forename: Mikhail Y
authors.initials: MY
authors.lastname: Lipin
authors.forename: Valerie
authors.initials: V
authors.lastname: Leuranguer
authors.forename: Eva
authors.initials: E
authors.lastname: Rozsa
authors.forename: Jayne R
authors.initials: JR
authors.lastname: Bramley
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Harding
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Reynolds
authors.forename: Jozsef
authors.initials: J
authors.lastname: Vigh
mesh_terms: D000465:Algorithms; D000818:Animals; D019771:Axotomy; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D003627:Data Interpretation, Statistical; D055724:Electrophysiological Phenomena; D005033:Ethylmaleimide / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D006054:Goldfish / Q000502:physiology*; D066298:In Vitro Techniques; D008027:Light; D009473:Neuronal Plasticity / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D012160:Retina / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D009603:Nitroso Compounds; D024642:Potassium Channels, Voltage-Gated; D009569:Nitric Oxide; D018698:Glutamic Acid; D006152:Cyclic GMP; D005033:Ethylmaleimide