March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Nicotinic Block Reduces Direction Selectivity to Moving Gratings by Increasing Amplitude and Shifting Phase of Null Direction Excitation
Author Affiliations & Notes
  • Mikhail Y. Lipin
    Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado
  • William R. Taylor
    Casey Eye Institute, Opthalmology, Oregon Health Sciences University, Portland, Oregon
  • Robert G. Smith
    Dept of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  Mikhail Y. Lipin, None; William R. Taylor, None; Robert G. Smith, None
  • Footnotes
    Support  NIH Grants EY016607 (RGS) and EY014888 (WRT)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6916. doi:
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      Mikhail Y. Lipin, William R. Taylor, Robert G. Smith; Nicotinic Block Reduces Direction Selectivity to Moving Gratings by Increasing Amplitude and Shifting Phase of Null Direction Excitation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6916.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : On-Off direction selective ganglion cells (DSGC) respond preferentially to motion in one direction. Responses in the opposite, null direction are suppressed by GABAergic inhibition from starburst amacrine cells (SBACs). SBACs also release acetylcholine, however, its role in generating direction selectivity (DS) is not well understood. Nicotinic antagonists do not much affect DS in the spike response to moving bars, but do suppress DS in response to drifting gratings (Grzywacz et al., 1998). The purpose of our study was to determine whether nicotinic block suppresses DS by altering the directional inhibition, the directional excitation, or both.

Methods: : We used whole-cell voltage clamp to record light-evoked responses of On-Off DSGCs (n=5 for each set of expts, in vitro whole-mount guinea pig retina, Ames medium, 35ºC). Moving sine gratings (50% contrast, 1 Hz, spatial period 100 or 200 µm) were presented for 120 s through a circular masking window with diameter 200 µm (to stimulate receptive field center) or 850 µm (to stimulate center and surround). The first 20 s were discarded to obviate adaptation effects. We applied conductance analysis to distinguish the excitatory and inhibitory inputs. To analyze the DSGC's performance, we applied ideal observer analysis to extracellular spike recordings. To block nicotinic receptors, we used 100 µM of hexamethonium + 30 nM methyllycaconitine.

Results: : Block of nicotinic receptors reduced DS in spike recordings with the 200 µm grating presented through the large window: the fraction of correct answers decreased decisively from 100% down to 67%. For the small window, the decrease in the fraction correct was less: from 99% down to 75%. In response to the 100 µm grating, the fraction correct decreased only for the large window (from 92% down to 81%), whereas for small window it hardly changed (68% vs. 73%). Nicotinic block decreased DS for the 200 µm grating and large window by increasing the null direction excitatory conductance by ~50%, but it decreased the preferred direction excitation insignificantly by 2%. This increased the number of spikes in the null direction, rather than decreasing the number of spikes in the preferred direction. Nicotinic block potentiated the inhibition without affecting its DS (33% null, 30% preferred). In the null direction, nicotinic block shifted the phase between the peak of excitation and the valley of inhibition 48°±22° to 0.7°±19° (mean±STD).

Conclusions: : Nicotinic block reduces direction selectivity in the DSGC in response to moving sine gratings by increasing the amplitude and shifting the phase of the null direction excitation, thus overcoming the inhibition.

Keywords: ganglion cells • acetylcholine • electrophysiology: non-clinical 
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