May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Visualization of Light and Ligand Activated Signaling in the Primate Retina
Author Affiliations & Notes
  • R.E. Marc
    Univ Utah, Salt Lake City, UT
  • B.W. Jones
    Univ Utah, Salt Lake City, UT
  • J.R. Anderson
    Univ Utah, Salt Lake City, UT
    Neuroscience Program,
  • D.W. Marshak
    Neurobiology & Anatomy, Univ Texas Med Sch, Houston, TX
  • Footnotes
    Commercial Relationships  R.E. Marc, Signature Immunologics, E; B.W. Jones, None; J.R. Anderson, None; D.W. Marshak, None.
  • Footnotes
    Support  NIH Grants EY02576 (RM), EY06472 (DM), EY014800 Vision Core (RM), Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 149. doi:
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      R.E. Marc, B.W. Jones, J.R. Anderson, D.W. Marshak; Visualization of Light and Ligand Activated Signaling in the Primate Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):149.

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

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Purpose: : To (1) compare the responses of various subclasses of ON and OFF bipolar cells (BCs) to sinusoidally modulated full–field light stimuli and (2) visualize functional display of alpha–amino–3hydroxyl–5–methylisoxazole–4–propionic acid (AMPA), kainate (KA), N–methyl–D–aspartate (NMDA) and group III metabotropic mGluR6 receptors in the primate retina.

Methods: : Isolated baboon (Papio anubis) eyecups or eyecup segments were incubated in a complete Ames medium augmented with 5 mM 1–amino–4–guanidobutane (AGB), an organic cation reporter that permeates glutamate–gated channels. Characteristic small molecule signatures and AGB signals were concurrently mapped by computational molecular phenotyping (CMP; Marc and Jones 2002 J Neurosci 22: 413). Signaling patterns were probed with 25 uM AMPA, 25 uM KA or 1 mM NMDA over a 10 min epoch or with 3 Hz sinusoidally modulated, broad–spectrum, low photopic light for 60–120 min.

Results: : AMPA/KA selectively activates horizontal cells and OFF BCs. Combined with CMP, this partitions non–foveal BC signaling pathways into distinct cone ON (31%), rod ON (30%) and AGB–labeled cone OFF (39%) populations. Multiple signal levels in the OFF BC cohort suggest that they express KA receptor (KAr) or AMPA receptor (AMPAr) displays that may support "range fractionation" or the separation of scene intensity components into several parallel channels. As in all other vertebrates examined so far, NMDA receptor (NMDAr) signaling is restricted to sets of amacrine cells (ACs) and ganglion cells (GCs) driven by cone BC channels. Light stimulation leads to activation of 100% of the BC population and virtually all ACs and GCs. Light–driven BC signaling clearly displays multiple signal–strengths, further supporting the range fractionation concept.

Conclusions: : (1) AGB mapping is an effective tool to track neuronal response patterns in the primate retina, whether triggered by exogenous ligands or endogenous synaptic pathways. (2) Both ON and OFF cone BC pathways show significant heterogeneity in responsivity to homogeneous stimulus events, arguing that parallel–channel range fractionation is enabled partly at the BC integration level. (3) Patterns of ligand–activated signaling in the primate retina match those of other mammals. (4) Together, light and ligand activation shows that AGB mapping of light–activated retina can concurrently track functional mGluR6–, AMPAr–, KAr– and NMDAr–gated pathways.

Keywords: bipolar cells • excitatory amino acid receptors • retinal connections, networks, circuitry 

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