Our broad goal is to investigate key 'design' principles by which the primate retina transfers large amounts of information to the brain. Its 106 axons are strikingly heterogeneous. They comprise 15 channels, spanning a 50-fold range in axon diameter and a 10-fold range in spike rate. Noting that foveal circuits are strongly constrained for space and energy, we hypothesize that multiple channels exist in order to relay information at least cost in """"""""wire volume' and metabolic energy. Preliminary studies suggest that channels transmitting at low information rates (few bits/second) are more efficient (more bits/spike) and physically smaller, thus using less space and probably less energy per bit. Thus central nuclei, which acquire information at different rates (e.g. geniculate M vs. K layers), can receive their messages at least cost. To test this, AIM 1 will measure for several ganglion cell types: (a) 'natural information rate' (bits/spike and bits/s in response to natural images); (b) total wire volume (soma + dendrites + axon + terminal arbor)(cell density); (c) relative energy costs, i.e., mitochondrial content. We predict that natural information rates differ strongly across channels and that 'low-rate' channels use less space and energy per bit. Noting that OFF channels are spatially finer and denser than ON channels and that 'blue/yellow' channels also occur on two spatial scales, we hypothesize that receptive field sizes and sampling rates are tuned to the distribution of information in natural scenes. To test this, AIM 2 will measure achromatic and chromatic information in natural images on scales corresponding to known receptive fields. We predict that in nature dark regions occupy higher spatial frequencies and contain more information per retinal area than bright regions and thus require finer channels with more synapses; there are analogous predictions for the blue/yellow channels. Noting that information transfer through the retina relies on 'ribbon' synapses, we hypothesize that they release and retrieve vesicles at very high rates. To test this, AIM 3 will measure release rates at the cone synapse (2-photon + electron microscopy of FM1-43 dye), and AIM 4 will measure the rates at the bipolar synapse (electrophysiology + EM of ferritin). Glaucoma, a major cause of blindness, has been attributed to both ganglion cell anoxia and reduced axonal transport. Our studies will relate ganglion cell signaling to both oxidative capacity and axonal transport capacity, and thus should extend the basic foundation for future clinical studies.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
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Mariani, Andrew P
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University of Pennsylvania
Schools of Medicine
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Perge, Janos A; Niven, Jeremy E; Mugnaini, Enrico et al. (2012) Why do axons differ in caliber? J Neurosci 32:626-38
Tkacik, Gasper; Garrigan, Patrick; Ratliff, Charles et al. (2011) Natural images from the birthplace of the human eye. PLoS One 6:e20409
Prentice, Jason S; Homann, Jan; Simmons, Kristina D et al. (2011) Fast, scalable, Bayesian spike identification for multi-electrode arrays. PLoS One 6:e19884
Herr, Steve; Ngo, Ivy Tran; Huang, Teresa M et al. (2011) Cone synapses in macaque fovea: II. Dendrites of OFF midget bipolar cells exhibit Inner Densities similar to their Outer synaptic Densities in basal contacts with cone terminals. Vis Neurosci 28:17-28
Schein, Stan; Ngo, Ivy Tran; Huang, Teresa M et al. (2011) Cone synapses in macaque fovea: I. Two types of non-S cones are distinguished by numbers of contacts with OFF midget bipolar cells. Vis Neurosci 28:3-16
Garrigan, Patrick; Ratliff, Charles P; Klein, Jennifer M et al. (2010) Design of a trichromatic cone array. PLoS Comput Biol 6:e1000677
Tkacik, Gasper; Prentice, Jason S; Balasubramanian, Vijay et al. (2010) Optimal population coding by noisy spiking neurons. Proc Natl Acad Sci U S A 107:14419-24
Tkacik, Gasper; Prentice, Jason S; Victor, Jonathan D et al. (2010) Local statistics in natural scenes predict the saliency of synthetic textures. Proc Natl Acad Sci U S A 107:18149-54
Lassova, Luisa; Fina, Marie; Sulaiman, Pyroja et al. (2010) Immunocytochemical evidence that monkey rod bipolar cells use GABA. Eur J Neurosci 31:685-96
Ratliff, Charles P; Borghuis, Bart G; Kao, Yen-Hong et al. (2010) Retina is structured to process an excess of darkness in natural scenes. Proc Natl Acad Sci U S A 107:17368-73

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