John E. Dowling

Bio: John E. Dowling is an academic researcher from Harvard University. The author has contributed to research in topics: Retina & Zebrafish. The author has an hindex of 94, co-authored 305 publications receiving 28116 citations. Previous affiliations of John E. Dowling include Marine Biological Laboratory & University of Cambridge.

Organization of the retina of the mudpuppy, Necturus maculosus. II. Intracellular recording.

Abstract: the optic nerve, it has been possible to specify many of the functions performed bv the vertebrate retina. These include brightness detection (16, 18, 27), centersurround contrast detection (1, 8, 20, 23), and motion detection (3, 4, 26-28). It has not been possible, however, to determine how the retina organizes the visual message recorded at the optic nerve, primarily because intracellular recording from single cells distal to the ganglion cells has been difficult. Detailed structural studies of the vertebrate retina, such as the one in the preceding paper (14), provide a framework within which the functional organization of the retina can be described. The anatomical studies show a limited number of clearly defined synaptic structures at which interaction between specific neurons can take place. In this paper we shall describe the intracellularly recorded response characteristics of each type of neuron in a vertebrate retina, and then relate the response of each neuron to the responses of those neurons to which it is synaptically coupled. By following the responses through the synaptic pathways, we can begin to describe how information from the visual field is abstracted and encoded in the retina. Intracellular recording throughout most retinas has been difficult because even the finest available micropipettes fail to penetrate the small retinal neurons consistently without damage. Bortoff (5-7) showed that this difficulty could be overcome by recording in an animal with larger retinal neurons: the mudpuppy, Nectwus maculosus. As described in the preceding paper (14),

The Retina: An Approachable Part of the Brain

Abstract: John Dowling's The Retina, published in 1987, quickly became the most widely recognized introduction to the structure and function of retinal cells. In this Revised Edition, Dowling draws on twenty-five years of new research to produce an interdisciplinary synthesis focused on how retinal function contributes to our understanding of brain mechanisms. The retina is a part of the brain pushed out into the eye during development. It retains many characteristics of other brain regions and hence has yielded significant insights on brain mechanisms. Visual processing begins there as a result of neuronal interactions in two synaptic layers that initiate an analysis of space, color, and movement. In humans, visual signals from 126 million photoreceptors funnel down to one million ganglion cells that convey at least a dozen representations of a visual scene to higher brain regions. The Revised Edition calls attention to general principles applicable to all vertebrate retinas, while showing how the visual needs of different animals are reflected in their retinal variations. It includes completely new chapters on color vision and retinal degenerations and genetics, as well as sections on retinal development and visual pigment biochemistry, and presents the latest knowledge and theories on how the retina is organized anatomically, physiologically, and pharmacologically. The clarity of writing and illustration that made The Retina a book of choice for a quarter century among graduate students, postdoctoral fellows, vision researchers, and teachers of upper-level courses on vision is retained in Dowling's new easy-to-read Revised Edition.

Organization of the primate retina: electron microscopy.

Abstract: The retinae of monkey and man have been studied by electron microscopy to identify cell types, their processes and synaptic contacts. In the inner plexiform layer, the morphological characteristics of the three types of cells (bipolar, ganglion and amacrine) are described and seven synaptic relationships are identified. The bipolar terminals contain ribbons at points of synaptic contact, and, at these points, there are typically two postsynaptic processes, one a ganglion cell dendrite, the other an amacrine cell process. This synaptic arrangement is here termed a dyad. The amacrine cell processes themselves make synaptic contacts with ganglion cell dendrites and somata, other amacrine cell processes, and, most frequently, with the bipolar cell terminals. Often, the amacrine-bipolar contact is adjacent to a bipolar-amacrine junction, forming a reciprocal synaptic arrangement between the bipolar and the amacrine. In the more peripheral retina, large bipolar cell terminals (probably of rod bipolars) are occasionally observed adjacent to the perikarya of the ganglion cells. At these junctions, areas of fusion between the plasma membranes are seen, suggesting that such axosomatic junctions could be electrical. In the outer plexiform layer, synapses have been identified only in the receptor cell bases where receptor cells contact bipolar and horizontal cell processes. Synaptic contacts of the horizontal cells have not been clearly identified, but their strategic terminations in the receptor cell ending are described and interpreted as possibly synaptic. A model of the retina, based on the described anatomy, is presented and correlated with ganglion cell physiology.

Inherited retinal dystrophy in the rat.

Abstract: Retinal dystrophies, known in man, dog, mouse, and rat, involve progressive loss of photoreceptor cells with onset during or soon after the developmental period. Functional (electroretinogram), chemical (rhodopsin analyses) and morphological (light and electron microscopy) data obtained in the rat indicated two main processes: (a) overproduction of rhodopsin and an associated abnormal lamellar tissue component, (b) progressive loss of photoreceptor cells. The first abnormality recognized was the appearance of swirling sheets or bundles of extracellular lamellae between normally developing retinal rods and pigment epithelium; membrane thickness and spacing resembled that in normal outer segments. Rhodopsin content reached twice normal values, was present in both rods and extracellular lamellae, and was qualitatively normal, judged by absorption maximum and products of bleaching. Photoreceptors attained virtually adult form and ERG function. Then rod inner segments and nuclei began degenerating; the ERG lost sensitivity and showed selective depression of the a-wave at high luminances. Outer segments and lamellae gradually degenerated and rhodopsin content decreased. No phagocytosis was seen, though pigment cells partially dedifferentiated and many migrated through the outer segment-debris zone toward the retina. Eventually photoreceptor cells and the b-wave of the ERG entirely disappeared. Rats kept in darkness retained electrical activity, rhodopsin content, rod structure, and extracellular lamellae longer than litter mates in light.

Intracellular responses of the Müller (glial) cells of mudpuppy retina: their relation to b-wave of the electroretinogram

Abstract: THE EI,ECTROKETI~‘~'~GRAM (ERG) was first recorded by Holmgren in 1865 (ZO), and it has proved to be a useful tool for studying retinal function for almost a century. Despite extensive studies, however, the cellular origins of the ERG components proximal to the receptors remain to be established. Quite recently it has become possible to record intracellularly from the retinal cells with fine micropipettes (2, 22, 34, 39), and thus the precise origins of the ERG components can now be investigated more directly. Our views on the components of the ERG are based mainly on the classic studies of Granit (19, 20). He analyzed the waveforms of the ERG into three components: an initial negative wave (PIII), which lasts the duration of the stimulus; an early transient positive wave (PII); and a late transient positive wave (PI). Granit (19) named these components in order of their sensitivity to ether narcosis. These components interact to produce the a, b, and c waves, respectively, of the intact ERG (16). PI (the c-wave) appears to originate in the pigment epithelium. Noel1 has shown that sodium iodate selectively abolishes the cwave as it destroys the pigment epithelial cells (27, 28). Also, Brown and Diesel (10) have reported intracellular records obtained from pigment epithelial cells and these records show a c-wave of reversed (negative) polarity with respect to the extracellular c-wave. Although the available evidence indicates the pigment epithelium as the probable c-wave generator, < the functional sig-

The Design and Analysis of Experiments

Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

Receptive fields and functional architecture of monkey striate cortex

Abstract: 1. The striate cortex was studied in lightly anaesthetized macaque and spider monkeys by recording extracellularly from single units and stimulating the retinas with spots or patterns of light. Most cells can be categorized as simple, complex, or hypercomplex, with response properties very similar to those previously described in the cat. On the average, however, receptive fields are smaller, and there is a greater sensitivity to changes in stimulus orientation. A small proportion of the cells are colour coded. 2. Evidence is presented for at least two independent systems of columns extending vertically from surface to white matter. Columns of the first type contain cells with common receptive-field orientations. They are similar to the orientation columns described in the cat, but are probably smaller in cross-sectional area. In the second system cells are aggregated into columns according to eye preference. The ocular dominance columns are larger than the orientation columns, and the two sets of boundaries seem to be independent. 3. There is a tendency for cells to be grouped according to symmetry of responses to movement; in some regions the cells respond equally well to the two opposite directions of movement of a line, but other regions contain a mixture of cells favouring one direction and cells favouring the other. 4. A horizontal organization corresponding to the cortical layering can also be discerned. The upper layers (II and the upper two-thirds of III) contain complex and hypercomplex cells, but simple cells are virtually absent. The cells are mostly binocularly driven. Simple cells are found deep in layer III, and in IV A and IV B. In layer IV B they form a large proportion of the population, whereas complex cells are rare. In layers IV A and IV B one finds units lacking orientation specificity; it is not clear whether these are cell bodies or axons of geniculate cells. In layer IV most cells are driven by one eye only; this layer consists of a mosaic with cells of some regions responding to one eye only, those of other regions responding to the other eye. Layers V and VI contain mostly complex and hypercomplex cells, binocularly driven. 5. The cortex is seen as a system organized vertically and horizontally in entirely different ways. In the vertical system (in which cells lying along a vertical line in the cortex have common features) stimulus dimensions such as retinal position, line orientation, ocular dominance, and perhaps directionality of movement, are mapped in sets of superimposed but independent mosaics. The horizontal system segregates cells in layers by hierarchical orders, the lowest orders (simple cells monocularly driven) located in and near layer IV, the higher orders in the upper and lower layers.

Inositol trisphosphate, a novel second messenger in cellular signal transduction.

Abstract: There has recently been rapid progress in understanding receptors that generate intracellular signals from inositol lipids. One of these lipids, phosphatidylinositol 4,5-bisphosphate, is hydrolysed to diacylglycerol and inositol trisphosphate as part of a signal transduction mechanism for controlling a variety of cellular processes including secretion, metabolism, phototransduction and cell proliferation. Diacylglycerol operates within the plane of the membrane to activate protein kinase C, whereas inositol trisphosphate is released into the cytoplasm to function as a second messenger for mobilizing intracellular calcium.

The structure of the nervous system of the nematode Caenorhabditis elegans

Abstract: The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a total complement of 302 neurons, which are arranged in an essentially invariant structure. Neurons with similar morphologies and connectivities have been grouped together into classes; there are 118 such classes. Neurons have simple morphologies with few, if any, branches. Processes from neurons run in defined positions within bundles of parallel processes, synaptic connections being made en passant. Process bundles are arranged longitudinally and circumferentially and are often adjacent to ridges of hypodermis. Neurons are generally highly locally connected, making synaptic connections with many of their neighbours. Muscle cells have arms that run out to process bundles containing motoneuron axons. Here they receive their synaptic input in defined regions along the surface of the bundles, where motoneuron axons reside. Most of the morphologically identifiable synaptic connections in a typical animal are described. These consist of about 5000 chemical synapses, 2000 neuromuscular junctions and 600 gap junctions.

The glutamate receptor ion channels

Abstract: The ionotropic glutamate receptors are ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the brain. The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992 ([Hollmann and Heinemann, 1994][1]), stimulated this