Gerald Jacobs - US grants

This program involves electrophysiological and behavioral studies of vision in species which have either highly cone-dominated or highly rod-dominated visual systems. These visual systems offer a number of special advantages in studying visual mechanisms, and the relationships between visual physiology and visual behavior. The specific research projects proposed include the following: (1) a determination of single cell responses in the ground squirrel to spatially and temporally defined luminance patterns and an inquiry into how such responses relate to discrimination behavior; (2) studies of the electrophysiology of the spectral mechanisms found in the ground squirrel visual system; (3) an examination of the receptive field organization of the lateral geniculate nucleus and visual cortex of the ground squirrel; (4) a study of spectral mechanisms and color vision in laboratory rats; (5) an investigation into the unusual properties which appear to be characteristic of the small number of rod photoreceptors found in the ground squirrel retina and (6) an investigation of the effects of spectrally restricted environments on the development and subsequent adult organization of the visual system.

It has been discovered that there are striking within-species variations in visual capacity among some species of South American monkeys, most notably the squirrel monkey (Saimiri sciureus). These variations include both visual sensitivity and color vision. Thus, it presently appears that as many as six different color vision phenotypes can be found in this species. Of interest is the fact that several of these types are closely similar in nature to the major variant types of color vision in man (i.e., protanopia, deuteranopia, protanomaly, deuteranomaly), and thus this species can serve as a unique biological model for the investigation of normal and defective color vision in man. The long-term objectives of this research are to provide accurate details about the nature of these within-species variations and to discover the biological mechanisms (Photopigment, neural, genetic) that account for these variations. The specific aims of the project are: (1) To further characterize the photopigments underlying color vision variations in primates by making microspectrophotometric measurements on monkeys whose color vision capacities differ in known ways, (2) To develop a noninvasive retinal gross potential measurement (the electroretinogram) so that it can be employed to rapidly and accurately determine the cone photopigment complement of individual retinas, (3) To evaluate through an examination of pedigrees a model for the inheritance of color vision in squirrel monkeys, (4) To examine the organization of the central visual system in conspecifics whose color vision capacities differ in known ways, through single unit electrophysiology and the tracing of projection pathways for color information, (5) to use behavioral tests to determine if other platyrrhine species show within-species variations in visual capacity similar to those so powerfully expresed in squirrel monkeys.

Recent results obtained from psychophysical experiment on humans and from molecular genetic experiments on human genomic DNA provide new insights into the relationships between the cone pigment genes, cone photopigments, and both normal and defective color vision. These results challenge several long-held ideas about the genetic basis of color vision and the photopigment basis of normal and defective color vision. The research provided here seeks to verify some of these new findings, offers a series of experiments to resolve some of the present ambiguities, and proposes tests of new hypotheses about the mechanisms for human color vision. The specific aims include: (a) further study of the characteristics of polymorphism of color vision among humans having normal color vision:; (b) an examination of the genetic basis of this polymorphism; (c) experiments to determine the nature of variation in the spectral mechanisms that account for dichromatic color vision; (d) an attempt to elucidate the relationship between X-chromosome photopigment genes and various types of defective color vision. Three techniques will be employed: (1) psychophysical tests of normal and color defective individuals, (2) examination of genomic Southern blots of DNA from subjects whose color vision has been carefully studied, (3) analysis of a retinal gross potential, the electroretinogram.

9318770 Jacobs Color vision is extremely valuable for discriminating objects and yielding information about the contents of objects. Primates are often considered to have the keenest sense of color among mammals, but we have data on only about 20 of the roughly 200 non-human primate species. Recent findings show that the distribution of two or three distinct photopigments, termed dichromacy or trichromacy respectively, is far more complex than earlier understood, with a genetic polymorphism in the types of pigment in the photoreceptor cone cells of the eye, showing a striking gender difference in the squirrel monkey. This project uses a portable, non-invasive set of electrophysiological and behavioral tests to evaluate the correctness of emerging views on primate color vision and its evolution. Species to be tested have been selected for particularly appropriate comparisons to rigorously examine the generalization about high individual variation among the group known as the New World monkeys, the generalization about little variation and human-like properties of trichromacy of the Old World monkeys, and to extend the very limited knowledge about the prosimians which are a very important group for understanding the evolutionary issues. The impact of these studies will continue to extend beyond visual neuroscience into anthropology, molecular evolution, and genetics, and the testing methodology may stimulate novel efficient tests for human adult and infant visual capabilities. ***

Significance Daylight vision results from the absorption of light by photosensitive pigments located in retinal cones. The spectral properties of these pigments limit sensitivity and determine the nature of color vision. Objectives Platyrrhine monkeys often show striking polymorphic variations I the complement of photopigments found in their cone photoceptors. These polymorphisms are directly linked to significant variations in color vision. The purpose of this research is to determine if Titi monkeys (Callicebus moloch) have cone photopigment polymorphisms and, if so, to understand the mechanisms underlying this variation. Results A nonevasive electrophysiological procedure, electroretinogram flicker photometry, was used to measure the photopigments in Titi monkeys. Like other platyrrhine monkeys, this species has a sex-linked photopigment polymorphism. All male monkeys have only two types of cone photopigments. This indicates that they will have dichromatic color vision. Among the males, five different phenotypes were detected. Most females have three different types of cone photopigments and, thus, will have trichromatic color vision. There is a significant variation among the females in the nature if the three pigments they possess. Examination of photopigment pedigrees provides evidence that these polymorphisms arise from X-linked opsin genes. The range of variation in this species is unique and thus provides fascinating evidence about the evolution of primate color vision. Future Directions Examination of the structure of the opsin genes of Titi monkeys will permit a better understanding of the relationships between genes, photopigments, and color vision in primates. KEY WORDS photopigment, opsin genes, color vision, evolution FUNDING National Science Foundation IBN-9318770

This research program is concerned with several fundamental aspects of the interrelationships between photopigments, neural organization, and visual behavior. One approach to analyzing these relationships is to utilize selected animal models that offer unique advantages that are often difficult to achieve in direct studies of human vision. The most prominent of these models is the New World monkey Saimiri sciureus (the squirrel monkey). This genus has a striking color vision polymorphism; the variant forms of this polymorphism have been much studied and they provide useful models for several aspects of human color vision. Research to be conducted falls into two major areas: (1) Development of the mechanisms underlying color vision. This research will seek to answer questions of how the neural connections necessary for color vision develop. To accomplish this a series of behavioral evaluations of simple and complex aspects of color vision will be conducted in squirrel monkeys, a species in which the relationship between X-chromosome gene action and photopigment specification allows the possibility of separating genetic and environmental influences in the development of short wavelength cone signals. In humans and other mammals the short-wavelength cone mechanism is relatively ineffective during the early development of color vision. This research will involve studies of the dichromatic ground squirrel to determine whether the source of that ineffectiveness is receptoral or a postreceptoral. (2) Investigations will be made of three fundamental aspects of the spectral properties of mammalian cone pigments. One investigation will collect and then examine spectra measured electrophysiologically from a large number of mammalian cone pigment types to determine if there are restrictions on the spectral positioning of mammalian cone pigments and, if so, what these restrictions are. A second investigation will seek to determine how much of the well-documented variations in cone- pigment based behavior, for example in human color matching, can be attributed to individual variations in cone pigment spectra. To accomplish this, electrophysiological measurements of cone spectra will be made in human protanopes. The experiment will be so designed that individual variations in cone spectra will be distinguishable from other sources of variation. A third investigation will seek to establish whether one form of human color vision defect, protanopia, can arise from more than one middle wavelength sensitive pigment. Preliminary results suggest that there may be polymorphic variants leading to protanopia.