Peter Sterling

Peter Sterling
University of Pennsylvania | UP · Department of Neuroscience

PhD

About

255
Publications
56,564
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Introduction
My lab studied neural circuits, leading finally to a book with Simon Laughlin, Principles of Neural Design. I am also a lifelong social activist, having campaigned for civil rights as a "Freedom Rider" and against the brain-damaging attempts to treat mental disturbance by psychosurgery, electroshock, and neuroleptic drugs. My new book, What is Health?/¿Qué es la Salud?, explains from molecules upward why we must abandon economic growth and restore daily small rewards for which we were wired.
Additional affiliations
July 1969 - June 2009
University of Pennsylvania
Position
  • professor of neuroscience

Publications

Publications (255)
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In Principles of Neural Design (2015, MIT Press), inspired by Charles Darwin, Sterling and Laughlin undertook the unfashionable task of distilling principles from facts in the technique-driven, data-saturated domain of neuroscience. Their starting point for deriving the organizing principles of brains are two brainless single-celled organisms, Esch...
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IN: Allostasis, Homeostasis, and the Costs of Adaptation J. Schulkin Cambridge University Press 2004 1 Principles of allostasis: optimal design, predictive regulation, pathophysiology and rational therapeutics.
Preprint
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The great ice-cream crisis Our nation is now preoccupied with the 'opioid crisis'. Understandably too, given that 64,000 citizens per year are dying suddenly, and 2.6 million are addicted to prescription opioid 'pain relievers' or street drugs such as heroin and fentanyl. The National Institutes of Health proposes to treat this crisis with more 'ed...
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The US National Academy of Sciences reports rising mortality for US adults, most steeply for Whites with secondary education or less. The rise is largely attributable to "deaths of despair" (suicide, alcohol and drug poisoning) with strong contributions from rising obesity. The NAS Report, while acknowledging a "crisis", proposes mild measures to m...
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Deaths of Despair (DoD), or mortality resulting from suicide, drug overdose, and alcohol related liver disease, have been rising steadily in the United States over the last several decades. In 2020, a record 186,763 annual despair-related deaths were documented, contributing to the longest sustained decline in US life expectancy since 1915-1918. Th...
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A critique of current biomedical response to rising US mortality and deaths of despair. Concludes with 4 principles for responding.
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Neuroscientists widely hypothesize that "depression" arises from a brain disorder caused by some defect in a specific neural pathway. If so, we might identify and localize the defect, and then develop a rational therapy. However, recent evidence from multiple sources fails to support this hypothesis: (1) Neuroimaging does not identify brain abnorma...
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The US National Academy of Sciences reports rising mortality for US adults, most steeply for White adults with a secondary education or less. The rise is largely attributable to deaths of despair (suicide and poisoning by alcohol and drugs) with strong contributions from the cardiovascular effects of rising obesity. Although the report does acknowl...
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Peter Sterling expands upon his recent Q & A article by discussing his participation in the Freedom Rides and the reasons for his involvement in the civil rights movement.
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Interview with Peter Sterling
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Interview with Peter Sterling, author of Principles of Neural Design and What Is Health?
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Blog piece explains that empathy is a fundamental trait -- but everyone gets a different dose.
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Recounts a morning of my "attention deficit disorder" and how it worked out.
Book
An argument that health is optimal responsiveness and is often best treated at the system level. Medical education centers on the venerable “no-fault” concept of homeostasis, whereby local mechanisms impose constancy by correcting errors, and the brain serves mainly for emergencies. Yet, it turns out that most parameters are not constant; moreover,...
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Although the concept of allostasis was proposed some 30 years ago, doubts persist about its precise meaning and whether it is useful. Here we review the concept in the context of recent studies as a strategy to efficiently regulate physiology and behavior. The brain, sensing the internal and external milieu, and consulting its database, predicts wh...
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Organisms evolving toward greater complexity were selected across aeons to use energy and resources efficiently. Efficiency depended on prediction at every stage: first a clock to predict the planet's statistical regularities; then a brain to predict bodily needs and compute commands that dynamically adjust the flows of energy and nutrients. Predic...
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Cutting down on long-distance air travel is the best way to reduce the emission of greenhouse gases by the scientific community.
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In this viewpoint, I tried to integrate my early studies of " alienation, " as Marx described it 150 years ago, with my lifelong professional studies on brain circuits. The result, I believe, helps to explain the explosive growth of consumption that drives the rise of atmospheric CO 2. The piece also reflects, although not explicitly, my last decad...
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Exponential economic growth is rapidly destabilizing the biosphere. Among the many factors that stimulate such growth is the human tendency to consume goods and services far beyond what is required to meet basic needs. We have to grasp what drives this tendency in order to manage it. The brain's core circuits were long believed to stimulate us to s...
Book
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Two distinguished neuroscientists distil general principles from more than a century of scientific study, “reverse engineering” the brain to understand its design. Neuroscience research has exploded, with more than fifty thousand neuroscientists applying increasingly advanced methods. A mountain of new facts and mechanisms has emerged. And yet a pr...
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Retinal and early central circuits match neural resources to the physical distribution of information in the environment. These circuits are optimized to package spatial and temporal information economically. The lateral geniculate circuit concentrates retinal information using a specialized, “quasi-secure” synapse. The geniculate neuron doubles bi...
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A protein circuit processes information like an electronic circuit -- by passing a signal through successive components that transform it according to their particular input-output (I/O) functions. The chemical binding and catalysis allow a range of molecular devices: amplifiers, oscillators, switches, level detectors, and so on. These compute dire...
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A neuron collects information cheaply via allosteric protein chemistry and integrates via analogue electrical signals in dendrites. Dendrites branch to expand information capacity by collecting more synapses with less wire. A neuron “complicates” it synaptic design by expressing diverse proteins to collect information across time scales, for exampl...
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Our brain outsmarts a supercomputer while using 100,000-fold less space and energy. It succeeds by hugging the linear region of the information rate vs. cost curve. The ways to do this constitute principles of neural design: improve S/N; reduce redundancy; sculpt messages to send only what is needed; send via parallel channels to match capacity to...
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Tiny organisms, such as the bacterium, E. coli, satisfy their metabolic needs within a restricted environment and a narrow range of conditions. They adapt to change via genetics and signal internally by chemical diffusion. Consequently, they have no use for a brain. Larger organisms, such as the protozoan, Paramecium caudatum (300,000-fold larger)...
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The brain regulates internal physiology and metabolism -- slow processes that can be modulated without any wire – just with cheap chemistry. The brain secretes hormone molecules into the blood -- which distribute slowly but without extra cost. Receptor proteins on the membranes of distant cells bind hormone molecules and thus receive information at...
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This chapter defines information with intuitive reasoning and simple equations. It then explains how information is transmitted by a protein molecule and also how the amount transmitted depends on signal statistics, noise, redundancy, and speed of response (bandwidth). Because a protein molecule binds a specific input to produce a specific output (...
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This chapter explains why certain sensors recode their graded signal directly to action potentials (olfactory); whereas others interpose one synaptic stage (auditory), and still others interpose two synaptic stages (visual). An olfactory sensor collects information at low bit rates, so it can transmit at low spike rates using a single thin axon. Bu...
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Photoreceptors use protein circuits to code efficiently. As light level changes, the circuits dynamically adapt gain and response speed to optimize coding. Mammalian rods specialize to code the sparse distribution of photons encountered in starlight by using high gain, slow response, and low noise. Their signaling proteins locate in larger compartm...
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Learning belongs to a broad principle of biological design: adapt, match, learn, and forget. Organisms respond to changed demands by re-sculpting at all levels to prepare for what will most likely be next. Physical exercise thickens skin and strengthens muscle; mental practice combined with motor practice refines neural circuits and thereby skills....
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Neural design is constrained by the substantial and irreducible resistance of neuronal cytoplasm. High resistance prevents neural wires from being any finer than they are, and it prevents local circuits from being any more voluminous than they are because larger circuits would cause excessive conduction delays. This constraint on local circuit volu...
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A fly gathers information for high-speed vision with fast, accurate photoreceptors. Information encoded at high rates is costly and must be preserved during transmission to interneurons by synaptic vesicles. For this the fly uses a special interface, the lamina, engineered for efficiency. High information rates are preserved by transmitting analogu...
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The retina in daylight resembles the camera on a planetary rover. Its cone photoreceptors capture rich images using chemistry (Chapter 8), but they are constrained to relay over a channel of low information capacity. Cone-driven circuits accomplish this economically and in real time (~100 ms) by following all ten principles of neural design. Follow...
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Engineers commonly disassemble a device to learn how it works. For example, Soviet engineers disassembled an American bomber to copy improvements in design. This process of “reverse engineering” depends upon a comprehensive knowledge of the principles governing design. For instance, engineers know “complicate but do not duplicate”. That is, design...
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Larger organisms explore a wider world and live longer, thereby expanding their possibilities for foraging but also their exposure to danger. Now a bigger brain becomes essential for sensing the environment and guiding behaviour. Behaviour must satisfy an animal’s internal systems, and internal systems must support behaviour. Thus the brain’s core...
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Most drugs that alter mental function, whether for recreational purposes or to treat mental disorders, affect synaptic transmission. Some drugs reshape the action potential, altering release of neurotransmitter; others antagonize or enhance the effect of a neurotransmitter on its synaptic receptor protein. Still other drugs inhibit reuptake of the...
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Thus, across a scale of one-million-fold—theUS mapped down to your house lot—we know the retina’sbasic design (Fig. 1).Some will object to this term, because it implies a designer.But to Webster, ‘‘design’’ is simply ‘‘outline showing the mainfeatures of something to be executed.’’ So now we can ask, justwhat is this ‘‘something to be executed’’? W...
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CNS axons differ in diameter (d) by nearly 100-fold (∼0.1-10 μm); therefore, they differ in cross-sectional area (d(2)) and volume by nearly 10,000-fold. If, as found for optic nerve, mitochondrial volume fraction is constant with axon diameter, energy capacity would rise with axon volume, also as d(2). We asked, given constraints on space and ener...
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Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured un...
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L and M cones, divided into two groups by absorption spectra, have not been distinguished by structure. Here, we report what may be such a difference. We reconstructed the synaptic terminals of 16 non-S cones and the dendritic arbors of their ON and OFF midget bipolar cells from high-magnification electron micrographs of serial thin sections of a s...
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As described in the companion paper, the synaptic terminal of a cone photoreceptor in macaque monkey makes an average of 35 or 46 basal contacts with the tips of the dendrites of its OFF midget bipolar cell. Each basal contact has one or more symmetrically thickened dense regions. These "Outer Densities," averaging 48 or 67 in number, harbor cluste...
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Retinal ganglion cells that respond selectively to a dark spot on a brighter background (OFF cells) have smaller dendritic fields than their ON counterparts and are more numerous. OFF cells also branch more densely, and thus collect more synapses per visual angle. That the retina devotes more resources to processing dark contrasts predicts that nat...
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Author Summary Human color perception arises by comparing the signals from cones with peak sensitivities, at long (L), medium (M) and short (S) wavelengths. In dichromats, a characteristic distribution of S and M cones supports blue-yellow color vision: a few S and mostly M. When L cones are added, allowing red-green color vision, the S proportion...
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In retinal bipolar neurons, synaptic ribbons mark the presence of exocytotic active zones in the synaptic terminal. It is unknown, however, where compensatory vesicle retrieval is localized in this cell type and by what mechanism(s) excess membrane is recaptured. To determine whether endocytosis is localized or diffuse in mouse bipolar neurons, we...
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Functional architecture of the striate cortex is known mostly at the tissue level--how neurons of different function distribute across its depth and surface on a scale of millimetres. But explanations for its design--why it is just so--need to be addressed at the synaptic level, a much finer scale where the basic description is still lacking. Funct...
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Fiber tracts should use space and energy efficiently, because both resources constrain neural computation. We found for a myelinated tract (optic nerve) that astrocytes use nearly 30% of the space and >70% of the mitochondria, establishing the significance of astrocytes for the brain's space and energy budgets. Axons are mostly thin with a skewed d...
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A low-contrast spot that activates just one ganglion cell in the retina is detected in the spike train of the cell with about the same sensitivity as it is detected behaviorally. This is consistent with Barlow's proposal that the ganglion cell and later stages of spiking neurons transfer information essentially without loss. Yet, when losses of sen...
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Most mammals are dichromats, having short-wavelength-sensitive (S) and middle-wavelength-sensitive (M) cones. Smaller terrestrial species commonly express a dual gradient in opsins, with M opsin concentrated superiorly and declining inferiorly, and vice-versa for S opsin. Some ganglion cells in these retinas combine S- and M-cone inputs antagonisti...
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The ribbon synapse can release a stream of transmitter quanta at very high rates. Although the ribbon tethers numerous vesicles near the presynaptic membrane, most of the tethered vesicles are held at a considerable distance from the plasma membrane. Therefore, it remains unclear how their contents are released. We evoked prolonged bouts of exocyto...
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Retinal ganglion cells comprise about 10 morphological types that also differ functionally. To determine whether functional differences might arise partially from differences in excitatory input, we quantified the distributions of ribbon contacts to four mammalian ganglion cell types [brisk-transient (BT), brisk-sustained (BS), local edge (LE), dir...
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Ribbon synapses release neurotransmitter continuously at high rates, and the ribbons tether a large pool of synaptic vesicles. To determine whether the tethered vesicles are actually released, we tracked vesicles labeled with styryl dye in mouse retinal bipolar cell terminals whose ribbons had been labeled with a fluorescent peptide. We photobleach...
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Retinal ganglion cells of a given type overlap their dendritic fields such that every point in space is covered by three to four cells. We investigated what function is served by such extensive overlap. Recording from pairs of ON or OFF brisk-transient ganglion cells at photopic intensities, we confirmed that this overlap causes the Gaussian recept...
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Design in engineering begins with the problem of robustness-by what factor should intrinsic capacity exceed normal demand? Here we consider robustness for a neural circuit that crosses the retina from cones to ganglion cells. The circuit's task is to represent the visual scene at many successive stages, each time by modulating a stream of stochasti...
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Rod and cone photoreceptors use specialized biochemistry to generate light responses that differ in their sensitivity and kinetics. However, it is unclear whether there are also synaptic differences that affect the transmission of visual information. Here, we report that in the dark, rods tonically release synaptic vesicles at a much slower rate th...
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Synaptic circuits in primate fovea have been quantified for midget/parvocellular ganglion cells. Here, based on partial reconstructions from serial electron micrographs, we quantify synaptic circuits for two other types of ganglion cell: the familiar parasol/magnocellular cell and a smaller type, termed "garland." The excitatory circuits both deriv...
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In guinea pig retina, immunostaining reveals a dual gradient of opsins: cones expressing opsin sensitive to medium wavelengths (M) predominate in the upper retina, whereas cones expressing opsin sensitive to shorter wavelengths (S) predominate in the lower retina. Whether these gradients correspond to functional gradients in postreceptoral neurons...
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The ganglion cell layer of mammalian retina contains numerous amacrine cells. Many belong to one type, the cholinergic starburst cell, but the other types have not been systematically identified. Using a new method to target sparsely represented cell types, we filled about 200 amacrine neurons in the ganglion cell layer of the guinea pig visual str...
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In the classic "What the frog's eye tells the frog's brain," Lettvin and colleagues showed that different types of retinal ganglion cell send specific kinds of information. For example, one type responds best to a dark, convex form moving centripetally (a fly). Here we consider a complementary question: how much information does the retina send and...
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How cone synapses encode light intensity determines the precision of information transmission at the first synapse on the visual pathway. Although it is known that cone photoreceptors hyperpolarize to light over 4-5 log units of intensity, the relationship between light intensity and transmitter release at the cone synapse has not been determined....
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Roughly half of all ganglion cells in mammalian retina belong to the broad class, termed "sluggish." Many of these cells have small receptive fields and project via lateral geniculate nuclei to visual cortex. However, their possible contributions to perception have been largely ignored because sluggish cells seem to respond weakly compared with the...
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Sensory neurons with short conduction distances can use nonregenerative, graded potentials to modulate transmitter release continuously. This mechanism can transmit information at much higher rates than spiking. Graded signaling requires a synapse to sustain high rates of exocytosis for relatively long periods, and this capacity is the special virt...
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Visual and auditory information is encoded by sensory neurons that tonically release neurotransmitter at high rates. The synaptic ribbon is an essential organelle in nerve terminals of these neurons. Its precise function is unknown, but if the ribbon could be visualized in a living terminal, both its own dynamics and its relation to calcium and ves...
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Retinal bipolar neurons release the excitatory transmitter, glutamate. However, certain bipolar cells contain GABA, raising the question whether a neuron might release both transmitters and, if so, what function might the inhibitory transmitter play in a particular circuit? Here we identify a subset of cone bipolar cells in cat retina that contain...
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INTRODUCTION This chapter compares two alternative models of physiological regulation. The first model, homeostasis (“stability through constancy”), has dominated physiology and medicine since Claude Bernard declared, “All the vital mechanisms … have only one object – to preserve constant the conditions of … the internal environment.” His dictum ha...
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A rule of retinal wiring is that many receptors converge onto fewer bipolar cells and still fewer ganglion cells. However, for each S cone in macaque fovea, there are two S-cone ON bipolar cells and two blue-yellow (BY) ganglion cells. To understand this apparent rule reversal, we reconstructed synaptic patterns of divergence and convergence and de...
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Different types of retinal ganglion cells convey different messages to the brain. Messages are in the form of spike patterns, and the number of possible patterns per second sets the coding capacity. We asked if different ganglion cell types make equally efficient use of their coding capacity or whether efficiency depends on the message conveyed. We...
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Synaptic vesicles are released stochastically, and therefore stimuli that increase a neuron's synaptic input might increase noise at its spike output. Indeed this appears true for neurons in primary visual cortex, where spike output variability increases with stimulus contrast. But in retinal ganglion cells, although intracellular recordings (with...
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G(o) is the most abundant G-protein in the brain, but its regulators are essentially unknown. In retina, Galpha(o1) is obligatory in mediating the metabotropic glutamate receptor 6 (mGluR6)-initiated ON response. To identify the interactors of G(o), we conducted a yeast two-hybrid screen with constituitively active Galpha(o) as a bait. The screen f...
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Cone photoreceptors tonically release neurotransmitter in the dark through a continuous cycle of exocytosis and endocytosis. Here, using the synaptic vesicle marker FM1-43, we elucidate specialized features of the vesicle cycle. Unlike retinal bipolar cell terminals, where stimulation triggers bulk membrane retrieval, cone terminals appear to exclu...
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The mammalian rod transfers a binary signal, the capture of 0 or 1 photon. In this issue of Neuron, Sampath and Rieke show in mouse that the rod's tonic exocytosis in darkness completely saturates a G protein cascade to close nearly all postsynaptic channels. A full-sized photon event supresses exocytosis sufficiently to allow approximately 30 post...
Chapter
The retina is a thin sheet of neural tissue lining the posterior hemisphere of the eye ball. It is actually part of the brain itself, evaginating from the lateral wall of the neural tube during embryonic development. The optic stalk grows out from the brain toward the ectoderm, inducing it to form an optical system (cornea, pupil, lens), which proj...
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An essential reference book for visual science. Visual science is the model system for neuroscience, its findings relevant to all other areas. This massive collection of papers by leading researchers in the field will become an essential reference for researchers and students in visual neuroscience, and will be of importance to researchers and prof...