The sensitivity of light-evoked responses of retinal ganglion cells is decreased in nitric oxide synthase gene knockout mice

Abstract

We have shown previously that increasing the production of nitric oxide (NO) results in a dampening of visual responses of retinal ganglion cells (G. Y. Wang, L. C. Liets, & L. M. Chalupa, 2003). To gain further insights into the role of NO in retinal function, we made whole-cell patch clamp recordings from ganglion cells of neural type nitric oxide synthase (nNOS) gene knockout mice. Here we show that in the dark-adapted state, the sensitivity of retinal ganglion cell to light stimulation is decreased in nNOS knockout animals. The lowest light intensities required to evoke optimal responses and the average intensities that evoked half-maximal responses were significantly higher in nNOS knockouts than in normal mice. Retinal histology and other features of light-evoked responses of ganglion cells in nNOS mice appeared to be indistinguishable from those of normal mice. Collectively, these results, in conjunction with our previous work, provide evidence that increasing levels of NO dampen visual responses of ganglion cells, while a lack of nNOS decreases the sensitivity of these neurons to light. Thus, NO levels in the retina are capable of modulating the information that ganglion cells convey to the visual centers of the brain.

Ideal observer analysis of signal quality in retinal circuits

“…These mechanisms can also be tested by ideal observer measurement of the performance of animal models with pharmacological block, or deletions of neuron types or specific mechanisms, e.g. connexins or synaptic proteins (Soucy et al, 1998; Strettoi et al, 2002; Shelley et al, 2006; Pang et al, 2007; Wang et al, 2007; Dedek et al, 2008; Kerschensteiner et al, 2008; Kim et al, 2008; Umino et al, 2008; Fadool & Dowling, 2008), or knock-ins of novel mechanisms (Bi et al, 2006). The ideal observer can explore models that include different noise sources, can determine the effect of each noise source on performance, and can compare their effects with a variety of circuits and stimuli.…”

Inhibition of nitric oxide synthase desensitizes retinal ganglion cells to light by diminishing their excitatory synaptic currents under light adaptation

“…The basic methods used in this study were similar to those used previously (Bai, Zhu, Yang, Savoie & Wang, 2009, Nemargut, Zhu, Savoie & Wang, 2009, Wang et al, 2007). All procedures were in compliance with National Institutes of Health guidelines and were approved by the campus animal use committees of Tulane University.…”

“…For each stimulus, the average peak firing rate was calculated by counting the number of spikes within a window that encompassed the highest firing rate, which occurred initially following the light onset or offset, and dividing the spike number by the duration of the window. The window was determined by the time period that most clustered spikes occurred and varied from cell to cell (Nemargut et al, 2009, Wang et al, 2003, Wang et al, 2007). The window endpoints corresponded to the time point where the frequency dropped by 15% of its highest frequency.…”

“…We have found that NO selectively blocked the APB sensitive rod Off-pathway while it has decreased most On responses in the dark-adapted retina (Wang, Liets & Chalupa, 2003). Additionally, we demonstrated that lack of nNOS reduced the sensitivity of RGCs to light under dark adaptation (Wang, van der List, Nemargut, Coombs & Chalupa, 2007). …”

Role of pH in a nitric oxide-dependent increase in cytosolic Cl−in retinal amacrine cells

“…Conversely, pharmacological inhibition of NO production decreased inhibition onto ganglion cells (Nemargut and Wang 2009). However, ganglion cells in neuronal NOS (nNOS) knockout retinas required more light than wild-type cells to respond optimally, indicating that completely removing nNOS-stimulated NO production also decreases ganglion cell activity (Wang et al 2007). Together, these findings indicate that in the inner retina, NO plays a complex role in shaping retinal output.…”