June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
NMDA receptors contribute to excitatory synaptic input to dopaminergic amacrine cells in the mouse retina
Author Affiliations & Notes
  • Lei-Lei Liu
    Eye Research Institute, Oakland University, Rochester, Michigan, United States
  • Nathan J Spix
    Eye Research Institute, Oakland University, Rochester, Michigan, United States
  • Dao-Qi Zhang
    Eye Research Institute, Oakland University, Rochester, Michigan, United States
  • Footnotes
    Commercial Relationships   Lei-Lei Liu, None; Nathan Spix, None; Dao-Qi Zhang, None
  • Footnotes
    Support  NIH Grant EY022640
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2974. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Lei-Lei Liu, Nathan J Spix, Dao-Qi Zhang; NMDA receptors contribute to excitatory synaptic input to dopaminergic amacrine cells in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2974.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Dopamine plays many important roles in visual function, including light adaptation. This neuromodulator is solely released by dopaminergic amacrine cells (DACs), which receive excitatory input from rods, cones and melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). These synaptic inputs are known to be mediated by AMPA-type glutamate receptors. In the present study, we examined whether NMDA-type glutamate receptors also contribute to the DAC synaptic input.

Methods : Wild-type and transgenic/mutant mice were used for immunohistochemical staining and whole-cell voltage clamp recordings, respectively. Melanopsin-based responses of DACs were isolated by genetic deletion of rod/cone function or in retinal degeneration 1 mice in which rods and cones had degenerated.

Results : Mg2+ is known to block NMDA receptors when the resting membrane potential is less than -40 mV. We found that removing Mg2+ from the extracellular medium significantly increased the peak amplitude of melanopsin-based responses of DACs at a holding potential of -70 mV (n=4). In the absence of Mg2+, the global NMDA receptor antagonist D-AP5 (50 μM) reduced melanopsin-based responses by 73% (n=6). We then isolated NMDA receptor-mediated melanopsin-based responses by blocking AMPA/KA receptors. We found that Con-T, a GluN2A/2B-containing receptor antagonist, almost abolished NMDA-receptor-mediated light responses (n=5), whereas the GluN2A-containing receptor antagonist NVP077 (n=3) or a GluN2B-containing receptor antagonist Con-G (n=3) partially suppressed the responses. Immunohistochemical staining suggested that both GluN2A and GluN2B subunits are expressed in DAC somas and processes. Finally, we unexpectedly observed that CNQX (100 μM), a classic AMPA/KA receptor antagonist, substantially suppressed NMDA receptor-mediated light responses of DACs (n=4).

Conclusions : Our results suggest that GluN2A/2B-containing NMDA receptors contribute to excitatory synaptic transmission to DACs, and may be involved in mediating synaptic plasticity of the dopaminergic network during light adaptation.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

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.

×