Faculty

Robert B Barlow, Ph.D. Professor, Ophthalmology Professor, Biochemistry and Molecular Biology 3258 Weiskotten Hall Upstate Medical University 750 East Adams Street Syracuse, NY 13210 (315) 464-7773

Education and Clinical Training

Research Program and Department Affiliations

Research Interests

Research Abstract

The Neural Code for Vision. With F. Dodge, E. Kim, E. Mole, C. Passaglia, K. Stewart

What information does the eye send to the brain when an animal sees? We are attempting to answer this question using as a model system the lateral eye of the horseshoe crab. The Limulus eye is indeed a suitable model, because more is known about its neural integrative mechanisms than those of any other eye, and a comprehensive cell-based model exists for the eye. We use the model to explore the neural responses transmitted by each of ~1,000 optic nerve fibers in the animal's brain when the animal sees.

Our approach is to record responses underwater from single optic-nerve fibers of the eye of a behaving animal, while also videotaping the eye's field of view using a miniature video camera attached to the animal's shell. The video images are then fed to the model eye which computes arrays of optic nerve activity or "neural images" of the underwater scenes. Confirmed by the single optic-nerve recordings, the neural images show that the eye functions as a filter which is tuned to objects having the size, contrast, and motion of potential mates. Without motion, the images of such objects fade.

These studies show that the eye is tuned for both spatial and temporal stimuli. The eye's acuity and lateral inhibition shape its sensitivity to spatial patterns of illumination; adaptive and transduction properties shape its sensitivity to temporally modulated light intensities. Operating together, these properties encode information about Limulus-like objects in the coherent activity of dynamic ensembles of retinal neurons, and transmit the information to the brain. The neural coding mechanisms of this relatively simple eye help explain how the animals use vision to detect mates. We are also studying how the brain processes the neural codes it receives from the eye.

Circadian Rhythms in the Limulus Visual System. With F. Dodge, C. Passaglia, M. Powers

A circadian clock in the Limulus brain modulates the structure and sensitivity of the retina. Our goal is to understand how the circadian clock adapts the animal's vision for essential tasks. Decreased noise and increased gain, and photon catch are major circadian changes found in photoreceptors. Noise reduction appears to result from the clock's stabilization of rhodopsin. Octopamine, hydrogen ions, and cAMP mediate the retinal circadian changes, which combine with dark adaptive mechanisms to increase retinal sensitivity up to 1,000,000 times at night and aid an animal's ability to find mates. A circadian clock in the brain of the horseshoe crab, Limulus polyphemus, transmits efferent optic-nerve signals to the lateral eyes at night, changing their structure and function, and increasing their sensitivity as much as 1,000,000 times over daytime levels. Our goal is to understand how these modulatory inputs adapt the animal's vision for essential tasks. Behavioral studies in the waters surrounding Woods Hole, MA, a natural habitat of the animal, show that the animals use their lateral eyes to find mates and do so equally well day and night. Circadian and noncircadian mechanisms appear to preserve the eye's contrast sensitivity day and night.

Molecular Origin of Photoreceptor Noise. With E. Mole, J. Schaefer, K. Mathiesz, V. Dionne, B. Knox

The human visual system can detect faint stars at night and distinguish objects in direct sunlight, for an effective operating range of about 10 log units of light intensity. At low light levels the key limiting factor is noise in photoreceptors caused by each photoreceptor eliciting false signals ("noise") which are indisguishable from the signals triggered by single photon absorptions. Limulus has evolved an exquisite circadian mechanism for reducing such photoreceptor noise at night. The circadian clock's output to the eye appears to lower photoreceptor noise by first lowering retinal pH, which in turn reduces the small (<0.01%) population of rhodopsin molecules with unprotonated schiff-base chromophores. protonating these molecules stabilizes them and thereby reduces the rate of noise events generated by photoreceptors in the dark. molecular orbital calculations and physiological studies of the retina support this mechanism. we are currently testing it with rigorous molecular biological techniques.thus far we have expressed limulusrhodopsin in Xenopus oocytes and shown that, after incubation with 11-cis retinal, the oocytes exhibit light-dependent ionic currents. We will combine the Xenopus oocyte expression system with site-directed mutagenesis of Limulus and Bovine rhodopsin to explore the molecular mechanisms underlying rhodopsin stability and photoreceptor noise.

Circadian and Efferent modulation of the Japanese Quail Retina. with N.Buelow, M.Iuvone, M.Kelly, M.Pierce, H.Uchiyama, H.Underwood

Circadian and Metabolic Modulation of Human Visual Sensitivity. With B. Farell, E.Boudreau, D.Moore, A. Lindstrom Human visual sensitivity depends on the time of day, blood glucose levels and ambient level of illumination.In measurements carried out over periods >24h, dark-adapted subjects experience as much as a 6-fold decrease in contrast sensitivity during their subjective night, with maximal changes occurring in the period of 0200 to 0400h. We measured contrast sensitivity with a highly sensitive, two-interval force-choice technique. In experiments restricted to the subjective day, we found that changing blood glucose levels in the range of 30 to ~200mg/dl by fasting, insulin injection, and/or the ingestion of glucose can produce more than a 10-fold change in contrast sensitivity. We are extending these preliminary studies to locate the site of action of glucose and assess with precision the circadian and metabolic influences on visual sensitivity.

fMRI Studies of Glucose Modulation of Human Brain Responses to Visual Stimuli. With E. Boudreau, D. Moore, S. Huckins, A. Lindstrom, D. Streeten, N. Szeverenyi, R. Weinstock

Glucose, a major energy source for brain function, can modulate human visual sensitivity. We studied whether changes in blood glucose can also modulate cortical activity in response to visual stimuli in subjects who had fasted overnight to induce mild hypoglycemia (~75mg/dl). fMRI reveals increased activation at the posterior occipital pole and in some cases along the calcarine fissure after blood glucose levels increased an average of 61 ±13mg/dl to 136 ±14mg/dl (n=6) which is equivalent to eating a substantial breakfast. We conclude that physiological changes in blood glucose levels can modulate cortical activity in response to visual stimuli. Whether these effects act pre- and/or post-synaptically in the cortex is not yet known. We are extending these studies with fMRI to determine the dose-dependence of blood glucose levels on brain activity at various times of the day and night.

Selected Reference

Umino Y, Everhart D, Solessio E, Cusato K, Pan JC, Nguyen TH, Brown E, Hafler R, Frio BA, Knox BE, Engbretson GA, Haeri M, Cui L, Glenn AS, Charron MJ, Barlow R: Hypoglycemia leads to
age-related loss of vision  PNAS December 19, 2006; 103:51 19541-19545

This profile was last updated on 09/29/2008

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