April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
A role for HCN channels in coordinating activity during glutamatergic retinal waves
Author Affiliations & Notes
  • Marla Feller
    Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA
    Vision Science Graduate Group, University of California, Berkeley, Berkeley, CA
  • Alana Firl
    Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA
    Vision Science Graduate Group, University of California, Berkeley, Berkeley, CA
  • Footnotes
    Commercial Relationships Marla Feller, None; Alana Firl, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3518. doi:
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      Marla Feller, Alana Firl; A role for HCN channels in coordinating activity during glutamatergic retinal waves. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3518.

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

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Abstract

Purpose: During the second postnatal week, transient glutamatergic circuits give rise to retinal waves, which are characterized by spontaneous depolarizations that propagate laterally across the retina. Previously, we showed that while retinal waves are accompanied by a large transient increase in extrasynaptic glutamate, only a subset of neurons in the ganglion cell layer (GCL) and inner nuclear layer (INL) participate in retinal waves. Inhibition is thought to play a role in determining which cells participate in waves, but the mechanism by which inhibition limits depolarization during waves remains unknown. Here we explore the relative role of excitation provided by bipolar cells and inhibition provided by amacrine in regulating the complex depolarization patterns of glutamatergic waves.

Methods: Spontaneous calcium transients of individual neurons in the INL and GCL were recorded with 2-photon calcium imaging. Short applications of glutamate (1mM) were delivered to the INL through a glass electrode using a PV820 pneumatic PicoPump. Participation of AII amacrine cells was monitored using the FBXO32 mouse, which expressed GFP in AII amacrine cells. We also examined the role of coordinated inhibition on the patterns of activation in both the INL and GCL with application of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 (50 µM).

Results: First, we found that short applications of exogenous glutamate did not initiate waves, indicating that excitatory input from bipolar cells is insufficient for initiating a wave. Second, using two-photon calcium imaging in FBXO32 mice, we determined that AII amacrine cells participate in glutamatergic waves. Third, we tested the role of HCN channels, which play a critical role in network entrainment in other neural circuits. Bath application of ZD7288 increased wave frequency and uncorrelated cell activity between waves in the GCL and INL. AII amacrine cells were desynchronized by ZD7288. Note, the effects of HCN blockade are different from the effects of inhibition blockade on waves, where the frequency of waves increases but there is no evidence of an increase in uncorrelated firing.

Conclusions: Our data indicate wave initiation and propagation is orchestrated by a coordinated circuit involving inhibitory interneurons. We propose a model in which glutamate release from bipolar cells is modulated by a network of inhibitory amacrine cells.

Keywords: 698 retinal development • 416 amacrine cells  
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