June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Astrocyte Gap Junction Protein Cx43 Modulates the Light Response of Mouse Retinal Ganglion Cells
Author Affiliations & Notes
  • Andrew Boal
    Medical Scientist Training Program, Vanderbilt University, Nashville, Tennessee, United States
    Neuroscience Graduate Program, Vanderbilt University, Nashville, Tennessee, United States
  • Nolan R McGrady
    Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Joseph M Holden
    Neuroscience Graduate Program, Vanderbilt University, Nashville, Tennessee, United States
  • Michael L Risner
    Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • David J Calkins
    Department of Ophthalmology and Visual Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Andrew Boal, None; Nolan McGrady, None; Joseph Holden, None; Michael Risner, None; David Calkins, None
  • Footnotes
    Support  NIH Grants EY017427, EY024997, EY008126, Research to Prevent Blindness Inc. Stein Innovation Award, Stanley Cohen Innovation Fund
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3038. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Andrew Boal, Nolan R McGrady, Joseph M Holden, Michael L Risner, David J Calkins; Astrocyte Gap Junction Protein Cx43 Modulates the Light Response of Mouse Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3038.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Astrocytes play key supportive roles in neuronal signaling, including providing metabolic support and buffering the extracellular environment. They form broad networks via gap junctions, primarily composed of the protein connexin-43 (Cx43). These networks allow the passage of important biomolecules between cells, connecting distant brain areas. This is a key component for the functioning of various neural circuits, such as in the hippocampus. However, it is less known how astrocyte networks affect retinal circuitry. Here, we evaluate the consequences of Cx43 knockout on the response properties of retinal ganglion cells (RGCs).

Methods : Conditional astrocytic Cx43 knockout (Cx43 -/-) was induced in GFAP-CreERT2/Cx43(fl/fl) mice by oral tamoxifen gavage. 1 week post-induction, mice were sacrificed and retinas were dissected in a dark room under red light. Retinas were constantly perfused with Ames’ medium supplemented with 20mM glucose. Whole-cell current clamp signals were amplified and digitized at a sampling rate of 50kHz. RGCs were classified by light response, dendritic stratification, and soma size. Cx43 -/- was confirmed by PCR. Recordings were analyzed using the pyABF package and custom python code, and statistical tests were done in GraphPad Prism.

Results : αON-S cells from Cx43 -/- mice showed an increased light response latency compared to WT controls (p = 0.002), though the rest of the light response was largely unaffected. αOFF-S cells, however, showed significant differences in light response between groups. αOFF-S cells from Cx43 -/- mice had a significantly lower spike rate (p = 0.02) and an increased response latency (p = 0.02). The hyperpolarizing response to light was also altered. Cells from Cx43 -/- mice had a lower mean amplitude of hyperpolarization (p = 0.04), although the peak amplitude was unchanged (p = 0.24). Cx43 -/- also affected RGC membrane properties. Cx43 -/- mice αON-S cells showed a steeper slope in the firing frequency vs. current relationship (p = 0.01) and had a higher overall spontaneous membrane potential variability (p = 0.01).

Conclusions : These results suggest that Cx43 -/- differentially alters the light response and membrane properties of RGCs. Thus, the astrocytic networks formed by Cx43 contribute significantly to RGC encoding of light.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×