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 (I Ca ) 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 I Ca modulation was cGMP independent but could be blocked by N-ethylmaleimide (

Calcium spike-mediated digital signaling increases glutamate output at the visual threshold of retinal bipolar cells

“…9B) than Na ϩ spikes described in mammalian BCs (Puthussery et al 2013;Saszik and DeVries 2012), suggesting that Ca 2ϩ spikes might be less suitable for signaling rapid changes within the visual field than Na ϩ spikes (Saszik and DeVries 2012). Although analysis of the temporal precision of spikes was not performed here, our data support this view: in Mbs, the jitter in the first spike delay not only increased with the reduction of light intensity (Tooker et al 2013; Fig. 8D) but at light intensities corresponding to the threshold of Mb signaling Ca 2ϩ spikes initiated after the termination of stimuli (Fig.…”

“…Ca 2ϩ spikes recorded from BCs in fish retinas code for high contrast and bright light with millisecond precision Tooker et al 2013). However, Ca 2ϩ spikes are much slower Protti et al 2000; Fig.…”

“…Trends of the series conductance (G s , middle) and membrane conductance (G m , bottom) were analyzed similarly. activation remained well below 1/R s (Tooker et al 2013), indicating a good voltage clamp (Marty and Neher 1995). R s Ͻ 30 M⍀ was not electronically compensated because it contributed Ͻ1% to membrane resistance (R m ) in axotomized Mb terminals (ϳ3-4 G⍀; Palmer et al 2003); therefore the compensation did not offer significant advantage.…”

“…Importantly, R s in all recordings was kept below 30 M⍀ (MATERIALS AND METHODS). This ensured that erroneous clamping of I Ca (Marty and Neher 1995) did not cause unwarranted sudden, sharp activation of I Ca in response to gradual V m changes of Mb terminals (Tooker et al 2013).…”

Manganese and Oxidative Stress

“…8,9 For example, H 2 O 2 (usually generated in mitochondria via dismutation of O 2 À ) modulates insulin release and signaling, adipocyte differentiation, regulation of cell cycle, and the hypoxic and immune responses. [10][11][12][13] Consequently, ROS signaling has been implicated in several events that can be advantageous to the cell.…”