Analysis and Synthesis of the Dynamic Response of Retinal Neurons

theory of linear systems analysis is developed in a form directly applicable to the treatment of the Limulus retina. The dynamics of the retina may conveniently be characterized by means of a spatiotemporal transfer function, which summarizes the response of the system to moving sinusoidal gratings ( analysis ). The response of the retina to an arbitrary stimulus may then be calculated by addition of the response to suitably weighted sinusoidal stimuli ( synthesis ). Responses were obtained from the in-situ retina by means of extracellular recording of impulse activity in single optic nerve fibers. Test ommatidia were chosen in the interior of the retina, to avoid asymmetries introduced by the edge of the retina. Stimuli which varied in both space and time were produced under computer control on the screen of a display oscilloscope, and were conveyed to the Limulus eye by means of a fiber-optic taper. Transfer functions were measured using counterphase modulation of cosine gratings according to a sum-of-sinusoids temporal signal, a procedure equivalent to the use of moving gratings, for ommatidia with symmetrical receptive fields. By means of these transfer functions, the responses of the Limulus eye to visual stimuli moving at various velocities were predicted in a parameter-free Fourier synthesis calculation. There was good agreement between these predictions and the measured responses to these stimuli. A quantitative model for the dynamic, integrative action of the Limulus retina is developed, based on the original formulation for the steady state given by the Hartline- Ratliff equations. The model comprises an excitatory generator potential, and dynamic processes of self and lateral inhibition. An explicit expression for the spatiotemporal transfer function is obtained in terms of transfer functions for the generator potential, self-inhibitory, and lateral-inhibitory transductions, and spatial transforms of the lateral inhibitory kernel and the point-spread characteristic of the experimental and physiological optics. Explicit functional forms for these component transductions are adopted. The parameters which occur in these expressions serve to incorporate information about the subcellular physiology of retinal neurons into the quantitative description of the function of the retina as a whole. Procedures are described for the estimation of these parameters from empirical transfer function data. Transfer functions calculated from the model on the basis of parameters obtained with these procedures show good agreement with the corresponding empirical transfer functions. The parameter values obtained in this way are, in general, quite consistent with the results of many more direct (and frequently more invasive) measurements reported in the literature. In particular, the inhibitory kernel, as determined from our transfer function measurements, shows a small crater in the vicinity of the test-ommatidium. The dynamical model can be used to describe the response of the retina in the vicinity of its boundary, as well as in the interior. An analysis, based on the Wiener-Hopf technique, is given for the response of peripheral retinal neurons. The predictions derived from this theory were compared with experiment through the use of illumination patterns in which one half of the retina was kept in darkness, while the remaining half was presented with a moving stimulus. This procedure permitted the calibration of model transfer functions by means of methods appropriate only for interior ommatidia, while simulating the neural environment at the edge of a homogeneous retina. Significant differences between the responses to stimuli which moved toward and away from the simulated edge were observed experimentally, in good agreement with the predictions of the theory. Similar behavior was also observed at the actual anatomical boundary of the eye

Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin.

Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor alphavbeta5 for particle binding. Here, we tested RPE phagocytosis and retinal function in beta5 integrin--deficient mice, which specifically lack alphavbeta5 receptors. Retinal photoresponses severely declined with age in beta5-/- mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. beta5-/- RPE in culture failed to take up isolated photoreceptor particles. beta5-/- RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in beta5-/- retina. These results demonstrate an essential role for alphavbeta5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the beta5-/- integrin mouse strain as a new animal model of age-related retinal dysfunction

Land use change in the river basins of the Great Barrier Reef, 1860 to 2019: a foundation for understanding environmental history across the catchment to reef continuum

Land use in the catchments draining to the Great Barrier Reef lagoon has changed considerably since the introduction of livestock grazing, various crops, mining and urban development. Together these changes have resulted in increased pollutant loads and impaired coastal water quality. This study compiled records to produce annual time-series since 1860 of human population, livestock numbers and agricultural areas at the scale of surface drainage river basins, natural resource management regions and the whole Great Barrier Reef catchment area. Cattle and several crops have experienced progressive expansion interspersed by declines associated with droughts and diseases. Land uses which have experienced all time maxima since the year 2000 include cattle numbers and the areas of sugar cane, bananas and cotton. A Burdekin Basin case study shows that sediment loads initially increased with the introduction of livestock and mining, remained elevated with agricultural development, and declined slightly with the Burdekin Falls Dam construction

Fine-suspended sediment and water budgets for a large, seasonally dry tropical catchment: Burdekin River catchment, Queensland, Australia

The Burdekin River catchment (~130,400 km2) is a seasonally dry tropical catchment located in north-east Queensland, Australia. It is the single largest source of suspended sediment to the Great Barrier Reef (GBR). Fine sediments are a threat to ecosystems on the GBR where they contribute to elevated turbidity (reduced light), sedimentation stress, and potential impacts from the associated nutrients. Suspended sediment data collected over a 5 year period were used to construct a catchment-wide sediment source and transport budget. The Bowen River tributary was identified as the major source of end-of-river suspended sediment export, yielding an average of 530 t km−2 yr−1 during the study period. Sediment trapping within a large reservoir (1.86 million ML) and the preferential transport of clays and fine silts downstream of the structure were also examined. The data reveal that the highest clay and fine silt loads—which are of most interest to environmental managers of the GBR—are not always sourced from areas that yield the largest total suspended sediment load (i.e., all size fractions). Our results demonstrate the importance of incorporating particle size into catchment sediment budget studies undertaken to inform management decisions to reduce downstream turbidity and sedimentation. Our data on sediment source, reservoir influence, and subcatchment and catchment yields will improve understandings of sediment dynamics in other tropical catchments, particularly those located in seasonally wet-dry tropical savannah/semiarid climates. The influence of climatic variability (e.g., drought/wetter periods) on annual sediment loads within large seasonally dry tropical catchments is also demonstrated by our data

Parallel Evolution of Tetrodotoxin Resistance in Three Voltage-Gated Sodium Channel Genes in the Garter Snake Thamnophis sirtalis

Members of a gene family expressed in a single species often experience common selection pressures. Consequently, the molecular basis of complex adaptations may be expected to involve parallel evolutionary changes in multiple paralogs. Here, we use bacterial artificial chromosome library scans to investigate the evolution of the voltage-gated sodium channel (Nav) family in the garter snake Thamnophis sirtalis, a predator of highly toxic Taricha newts. Newts possess tetrodotoxin (TTX), which blocks Nav’s, arresting action potentials in nerves and muscle. Some Thamnophis populations have evolved resistance to extremely high levels of TTX. Previous work has identified amino acid sites in the skeletal muscle sodium channel Nav1.4 that confer resistance to TTX and vary across populations. We identify parallel evolution of TTX resistance in two additional Nav paralogs, Nav1.6 and 1.7, which are known to be expressed in the peripheral nervous system and should thus be exposed to ingested TTX. Each paralog contains at least one TTX-resistant substitution identical to a substitution previously identified in Nav1.4. These sites are fixed across populations, suggesting that the resistant peripheral nerves antedate resistant muscle. In contrast, three sodium channels expressed solely in the central nervous system (Nav1.1–1.3) showed no evidence of TTX resistance, consistent with protection from toxins by the blood–brain barrier. We also report the exon–intron structure of six Nav paralogs, the first such analysis for snake genes. Our results demonstrate that the molecular basis of adaptation may be both repeatable across members of a gene family and predictable based on functional considerations

A Proposal to Sequence the Genome of a Garter Snake (Thamnophis sirtalis)

Here we develop an argument in support of sequencing a garter snake (Thamnophis sirtalis) genome, and outline a plan to accomplish this. This snake is a common, widespread, nonvenomous North American species that has served as a model for diverse studies in evolutionary biology, physiology, genomics, behavior and coevolution. The anole lizard is currently the only genome sequence available for a non-avian reptile. Thus, the garter snake at this time would be the first available snake genome sequence and as such would provide much needed comparative representation of non-avian reptilian genomes, and would also allow critical new insights for vertebrate comparative genomic studies. We outline the major areas of discovery that the availability of the garter snake genome would enable, and describe a plan for whole-genome sequencing.Organismic and Evolutionary Biolog

Brane World Susy Breaking from String/M Theory

String and M-theory realizations of brane world supersymmetry breaking scenarios are considered in which visible sector Standard Model fields are confined on a brane, with hidden sector supersymmetry breaking isolated on a distant brane. In calculable examples with an internal manifold of any volume the Kahler potential generically contains brane--brane non-derivative contact interactions coupling the visible and hidden sectors and is not of the no-scale sequestered form. This leads to non-universal scalar masses and without additional assumptions about flavor symmetries may in general induce dangerous sflavor violation even though the Standard Model and supersymmetry branes are physically separated. Deviations from the sequestered form are dictated by bulk supersymmetry and can in most cases be understood as arising from exchange of bulk supergravity fields between branes or warping of the internal geometry. Unacceptable visible sector tree-level tachyons arise in many models but may be avoided in certain classes of compactifications. Anomaly mediated and gaugino mediated contributions to scalar masses are sub-dominant except in special circumstances such as a flat or AdS pure five--dimensional bulk geometry without bulk vector multiplets.Comment: Latex, 83 pages, references adde

Tongue volume and the mandibular dentition

A method utilizing the principle of fluid displacement was devised to measure the volume of the anterior portion of the tongue.A sample of thirty-nine men was used to test the relationships between measurable tongue volume, tongue length, certain angular cephalometric measurements, and lower arch dimensions. Seventeen subjects showing scalloping of the lateral borders of the tongue were compared with the main sample.Conclusions from this investigation are as follows: 1. 1. The volume of the anterior portion of the tongue can be measured with an average accuracy of 2.3 c.c. +/- 1.4 c.c., using the instrument described here.2. 2. In this sample, and with this method of measurement, the volume and length of the tongue seem to have little, if any, influence on the width and length of the lower dental arch, on the degree of interincisal relationship, and on the angle of the lower incisor teeth to the mandibular plane.3. 3. A statistically significant correlation of 0.4 exists between measurable tongue volume and arch perimeter.4. 4. Scalloping of the tongue does not appear to be an indication of a large tongue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32920/1/0000302.pd