April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Kainate Receptors Mediate Signaling in Both Transient and Sustained OFF Bipolar Cell Pathways in the Mouse Retina
Author Affiliations & Notes
  • Bart Gerard Borghuis
    Anatomical Science and Neurobiology, University of Louisville, Louisville, KY
    Ophthalmology and Visual Science, Yale University, New Haven, CT
  • Loren L Looger
    Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, VA
  • Susumu Tomita
    Department of Cellular and Molecular Physiology, Yale University, New Haven, CT
    Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University, New Haven, CT
  • Jonathan B Demb
    Ophthalmology and Visual Science, Yale University, New Haven, CT
  • Footnotes
    Commercial Relationships Bart Borghuis, Borghuis Instruments (I); Loren Looger, None; Susumu Tomita, None; Jonathan Demb, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4527. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Bart Gerard Borghuis, Loren L Looger, Susumu Tomita, Jonathan B Demb; Kainate Receptors Mediate Signaling in Both Transient and Sustained OFF Bipolar Cell Pathways in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4527.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we evaluated the contribution of AMPA and kainate receptors to light-evoked responses of OFF bipolar cells in the whole-mount mouse retina.

Methods: We measured light-evoked (λmax 395 nm) glutamate release from bipolar cells in the mouse retina in vitro, by two-photon fluorescence imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. We perturbed AMPA and kainate receptor function using non-selective (DNQX: 100 μM) or selective blockers (AMPA: 100 μM GYKI 52466, 100 μM GYKI 53655; kainate: 50 μM UBP310, 1 μM ACET); L-AP4 (20 μM) was used to block the ON pathway. To validate and complement imaging experiments, excitatory currents were recorded from ganglion and bipolar cells with targeted whole-cell recordings.

Results: Light-evoked glutamate release persisted at all OFF levels of the inner plexiform layer in the presence of DNQX but was abolished by subsequent application of L-AP4, indicating that cross-over inhibition from DNQX-resistant ON pathways can drive release from bipolar terminals throughout the OFF layers. In subsequent recordings we first applied L-AP4 to isolate OFF responses mediated by the cone→OFF bipolar cell synapse. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors, but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated contrast responses at temporal frequencies up to 20 Hz, exceeding the limits implied by the time constant for recovery from desensitization measured previously (0.5 - 1.5 s).

Conclusions: Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.

Keywords: 435 bipolar cells • 693 retinal connections, networks, circuitry • 675 receptors: pharmacology/physiology  
×
×

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.

×