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Biomedical subjects

Robert G Smith

Publications and source records attributed to Robert G Smith.

17 recordsLinked to original sources
PubMed2005

Voltage-gated sodium channels improve contrast sensitivity of a retinal ganglion cell.

Voltage-gated channels in a retinal ganglion cell are necessary for spike generation. However, they also add noise to the graded potential and spike train of the ganglion cell, which may degrade its contrast sensitivity, and they may also amplify the graded potential signal. We studied the effect of blocking Na+ channels in a ganglion cell on its signal and noise amplitudes and its contrast sensitivity. A spot was flashed at 1-4 Hz over the receptive field center of a brisk transient ganglion cell in an intact mammalian retina maintained in vitro. We measured signal and noise amplitudes from its intracellularly recorded graded potential light response and measured its contrast detection thresholds with an "ideal observer." When Na+ channels in the ganglion cell were blocked with intracellular lidocaine N-ethyl bromide (QX-314), the signal-to-noise ratio (SNR) decreased (p < 0.05) at all tested contrasts (2-100%). Likewise, bath application of tetrodotoxin (TTX) reduced the SNR and contrast sensitivity but only at lower contrasts (< or = 50%), whereas at higher contrasts, it increased the SNR and sensitivity. The opposite effect of TTX at high contrasts suggested involvement of an inhibitory surround mechanism in the inner retina. To test this hypothesis, we blocked glycinergic and GABAergic inputs with strychnine and picrotoxin and found that TTX in this case had the same effect as QX-314: a reduction in the SNR at all contrasts. Noise analysis suggested that blocking Na+ channels with QX-314 or TTX attenuates the amplitude of quantal synaptic voltages. These results demonstrate that Na+ channels in a ganglion cell amplify the synaptic voltage, enhancing the SNR and contrast sensitivity.

Action Potentials↗
PubMed2004

Sluggish and brisk ganglion cells detect contrast with similar sensitivity.

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 more easily studied "brisk" cells. By selecting small somas under infrared DIC optics and recording with a loose seal, we could routinely isolate sluggish cells. When a spot was matched spatially and temporally to the receptive field center, most sluggish cells could detect the same low contrasts as brisk cells. Detection thresholds for the two groups determined by an "ideal observer" were similar: threshold contrast for sluggish cells was 4.7 +/- 0.5% (mean +/- SE), and for brisk cells was 3.4 +/- 0.3% (Mann-Whitney test: P > 0.05). Signal-to-noise ratios for the two classes were also similar at low contrast. However, sluggish cells saturated at somewhat lower contrasts (contrast for half-maximum response was 14 +/- 1 vs. 19 +/- 2% for brisk cells) and were less sensitive to higher temporal frequencies (when the stimulus frequency was increased from 2 to 4 Hz, the response rate fell by 1.6-fold). Thus the sluggish cells covered a narrower dynamic range and a narrower temporal bandwidth, consistent with their reported lower information rates. Because information per spike is greater at lower firing rates, sluggish cells may represent "cheaper" channels that convey less urgent visual information at a lower energy cost.

Action Potentials↗
PubMed2004

Spike generator limits efficiency of information transfer in a retinal ganglion cell.

The quality of the signal a retinal ganglion cell transmits to the brain is important for preception because it sets the minimum detectable stimulus. The ganglion cell converts graded potentials into a spike train with a selective filter but in the process adds noise. To explore how efficiently information is transferred to spikes, we measured contrast detection threshold and increment threshold from graded potential and spike responses of brisk-transient ganglion cells. Intracellular responses to a spot flashed over the receptive field center of the cell were recorded in an intact mammalian retina maintained in vitro at 37 degrees C. Thresholds were measured in a single-interval forced-choice procedure with an ideal observer. The graded potential gave a detection threshold of 1.5% contrast, whereas spikes gave 3.8%. The graded potential also gave increment thresholds approximately twofold lower and carried approximately 60% more gray levels. Increment threshold "dipped" below the detection threshold at a low contrast (<5%) but increased rapidly at higher contrasts. The magnitude of the "dipper" for both graded potential and spikes could be predicted from a threshold nonlinearity in the responses. Depolarization of the cell by current injection reduced the detection threshold for spikes but also reduced the range of contrasts they can transmit. This suggests that contrast sensitivity and dynamic range are related in an essential trade-off.

Action Potentials↗
PubMed2004

Design for a binary synapse.

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 postsynaptic channels to open simultaneously. Thus, the synapse behaves like a digital gate, whose hallmark is reliability and resistance to noise.

Animals↗
PubMed2004

Transmission of scotopic signals from the rod to rod-bipolar cell in the mammalian retina.

Mammals can see at low scotopic light levels where only 1 rod in several thousand transduces a photon. The single photon signal is transmitted to the brain by the ganglion cell, which collects signals from more than 1000 rods to provide enough amplification. If the system were linear, such convergence would increase the neural noise enough to overwhelm the tiny rod signal. Recent studies provide evidence for a threshold nonlinearity in the rod to rod bipolar synapse, which removes much of the background neural noise. We argue that the height of the threshold should be 0.85 times the amplitude of the single photon signal, consistent with the saturation observed for the single photon signal. At this level, the rate of false positive events due to neural noise would be masked by the higher rate of dark thermal events. The evidence presented suggests that this synapse is optimized to transmit the single photon signal at low scotopic light levels.

Amacrine Cells↗
PubMed2003

Timing of quantal release from the retinal bipolar terminal is regulated by a feedback circuit.

In isolation, a presynaptic terminal generally releases quanta according to Poisson statistics, but in a circuit its release statistics might be shaped by synaptic interactions. We monitored quantal glutamate release from retinal bipolar cell terminals (which receive GABA-ergic feedback from amacrine cells) by recording spontaneous EPSCs (sEPSCs) in their postsynaptic amacrine and ganglion cells. In about one-third of these cells, sEPSCs were temporally correlated, arriving in brief bursts (10-55 ms) more often than expected from a Poisson process. Correlations were suppressed by antagonizing the GABA(C) receptor (expressed on bipolar terminals), and correlations were induced by raising extracellular calcium or osmolarity. Simulations of the feedback circuit produced "bursty" release when the bipolar cell escaped intermittently from inhibition. Correlations of similar duration were present in the light-evoked sEPSCs and spike trains of sluggish-type ganglion cells. These correlations were suppressed by antagonizing GABA(C) receptors, indicating that glutamate bursts from bipolar terminals induce spike bursts in ganglion cells.

Action Potentials↗
PubMed2003

Contrast threshold of a brisk-transient ganglion cell in vitro.

We measured the contrast threshold for mammalian brisk-transient ganglion cells in vitro. Spikes were recorded extracellularly in the intact retina (guinea pig) in response to a spot with sharp onset, flashed for 100 ms over the receptive field center. Probability density functions were constructed from spike responses to stimulus contrasts that bracketed threshold. Then an "ideal observer" (IO) compared additional trials to these probability distributions and decided, using a single-interval, two-alternative forced-choice procedure, which contrasts had most likely been presented. From these decisions we constructed neurometric functions that yielded the threshold contrast by linear interpolation. Based on the number of spikes in a response, the IO detected contrasts as low as 1% [4.2 +/- 0.4% (SE); n = 35]; based on the temporal pattern of spikes, the IO detected contrasts as low as 0.8% (2.8 +/- 0.2%). Contrast increments above a very low "basal contrast" were discriminated with greater sensitivity than they were detected against the background. Performance was optimal near 37 degrees C and declined with a Q(10) of about 2, similar to that of retinal metabolism. By the method used by previous in vivo studies of brisk-transient cells, our most sensitive cells had similar thresholds. The in vitro measurements thus provide an important benchmark for comparing sensitivity of neurons upstream (cone and bipolar cell) and downstream to assess efficiency of retinal and central circuits.

Algorithms↗
PubMed2003

Validation of Wagner's classification: a literature review.

To ensure high quality care, practitioners should base their practice on sound clinical evidence. Relying on quantitative measurements when evaluating this evidence demands measurement accuracy, reliability, and validity. Current diabetic foot ulcer classification systems include: Meggitt's, Wagner's, Knighton's, Pecoraro's, University of Texas San Antonio Diabetic Wound Classification, and Size (Area and Depth), Sepsis, Arteriopathy, and Denervation. Of these, the Wagner's classification system is the most widely used to describe the natural history of the dysvascular foot, even though evidence of its validity and reliability are lacking. A review of clinimetric properties and existing validation literature of the other diabetic classification systems suggest that the University of Texas San Antonio Diabetic Wound Classification and S(AD) SAD have the potential to fill the current void, once additional studies have been conducted.

Diabetic Foot↗
PubMedDate not supplied

Direction selectivity in a model of the starburst amacrine cell.

The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in On-Off direction-selective ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not shown robust direction selectivity (DS), the dendritic tips of these cells display direction-selective calcium signals, even when gamma-aminobutyric acid (GABAa,c) channels are blocked, implying that inhibition is not necessary to generate DS. This suggested that the distinctive morphology of the SBAC could generate a DS signal at the dendritic tips, where most of its synaptic output is located. To explore this possibility, we constructed a compartmental model incorporating realistic morphological structure, passive membrane properties, and excitatory inputs. We found robust DS at the dendritic tips but not at the soma. Two-spot apparent motion and annulus radial motion produced weak DS, but thin bars produced robust DS. For these stimuli, DS was caused by the interaction of a local synaptic input signal with a temporally delayed "global" signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic tips coincided, allowing summation, whereas in the null direction the local signal preceded the global signal, preventing summation. Sine-wave grating stimuli produced the greatest amount of DS, especially at high velocities and low spatial frequencies. The sine-wave DS responses could be accounted for by a simple mathematical model, which summed phase-shifted signals from soma and dendritic tip. By testing different artificial morphologies, we discovered DS was relatively independent of the morphological details, but depended on having a sufficient number of inputs at the distal tips and a limited electrotonic isolation. Adding voltage-gated calcium channels to the model showed that their threshold effect can amplify DS in the intracellular calcium signal.

Amacrine Cells↗
PubMedDate not supplied

Transmission of single photon signals through a binary synapse in the mammalian retina.

At very low light levels the sensitivity of the visual system is determined by the efficiency with which single photons are captured, and the resulting signal transmitted from the rod photoreceptors through the retinal circuitry to the ganglion cells and on to the brain. Although the tiny electrical signals due to single photons have been observed in rod photoreceptors, little is known about how these signals are preserved during subsequent transmission to the optic nerve. We find that the synaptic currents elicited by single photons in mouse rod bipolar cells have a peak amplitude of 5-6 pA, and that about 20 rod photoreceptors converge upon each rod bipolar cell. The data indicates that the first synapse, between rod photoreceptors and rod bipolar cells, signals a binary event: the detection, or not, of a photon or photons in the connected rod photoreceptors. We present a simple model that demonstrates how a threshold nonlinearity during synaptic transfer allows transmission of the single photon signal, while rejecting the convergent neural noise from the 20 other rod photoreceptors feeding into this first synapse.

Animals↗
PubMedDate not supplied

Postsynaptic calcium feedback between rods and rod bipolar cells in the mouse retina.

Light-evoked currents were recorded from rod bipolar cells in a dark-adapted mouse retinal slice preparation. Low-intensity light steps evoked a sustained inward current. Saturating light steps evoked an inward current with an initial peak that inactivated, with a time constant of about 60-70 ms, to a steady plateau level that was maintained for the duration of the step. The inactivation was strongest at hyperpolarized potentials, and absent at positive potentials. Inactivation was mediated by an increase in the intracellular calcium concentration, as it was abolished in cells dialyzed with 10 mM BAPTA, but was present in cells dialyzed with 1 mM EGTA. Moreover, responses to brief flashes of light were broader in the presence of intracellular BAPTA indicating that the calcium feedback actively shapes the time course of the light responses. Recovery from inactivation observed for paired-pulse stimuli occurred with a time constant of about 375 ms. Calcium feedback could act to increase the dynamic range of the bipolar cells, and to reduce variability in the amplitude and duration of the single-photon signal. This may be important for nonlinear processing at downstream sites of convergence from rod bipolar cells to AII amacrine cells. A model in which intracellular calcium rapidly binds to the light-gated channel and reduces the conductance can account for the results.

Animals↗
PubMedDate not supplied

Vancomycin: an overview for the podiatric physician.

An increased reliance on vancomycin to treat bacterial infections has led to the emergence of vancomycin-resistant organisms. The podiatric physician must select and use vancomycin with due caution. This article presents a general review of vancomycin's pharmacology, pharmacokinetics, and dosing recommendations. Literature citations of clinically based evidence regarding the development and use of vancomycin nomograms are also presented. A vancomycin dosing nomogram is introduced as an effective tool for the prescribing podiatric physician. Appropriate use of the information presented may improve patient outcomes and enable the podiatric physician to treat patients with less effort and at a lower cost.

Anti-Bacterial Agents↗
PubMedDate not supplied

A critical discussion of the use of antiseptics in acute traumatic wounds.

Approximately 10 million patients with traumatic wounds are treated in US emergency departments annually. The practice of wound cleansing or antiseptic management has a dichotomous history anchored in tradition and science. The merits of antiseptic fluid irrigation of traumatic wounds have received little scientific study. The purpose of this article is to critically evaluate the potential harm to patient outcome by the use of antiseptics on acute wounds. First, animal and cell culture data that describe the effects of topical antiseptics on wound healing are offered. Second, human case studies are presented to illustrate the potential harm of the indiscriminate use of antiseptics. Finally, data from previously published reviews are presented and evaluated for clinically based evidence to justify the current practice of antiseptic use in acute traumatic wounds.

Acute Disease↗
PubMedDate not supplied

Low-molecular-weight heparins: an overview for the podiatric physician.

Deep venous thrombosis is a common but underdiagnosed medical condition. The epidemiologic features, economic impact, morbidity, and mortality of venous thromboembolism make it imperative that the podiatric physician be familiar with its pathogenesis as well as its pharmacologic treatment. Medical literature rooted in clinical evidence has demonstrated that low-molecular-weight heparins are safe and effective for the prevention and treatment of venous thromboembolism. The primary purpose of this article is to review the pharmacologic characteristics of low-molecular-weight heparins. Dosing recommendations for low-molecular-weight heparins as they apply to the prevention of deep venous thrombosis are presented. Finally, a dosing criteria chart is presented to assist the podiatric physician in prescribing and evaluating low-molecular-weight heparins as a therapeutic class.

Anticoagulants↗
PubMedDate not supplied

Fall-contributing adverse effects of the most frequently prescribed drugs.

The 200 most frequently prescribed medications in 2000 were reviewed for adverse effects that have the potential to cause fall injuries. The actual number of different medications reviewed was 169 after eliminating duplicates due to listing of medications by both brand and generic names. Of these 169 medications, adverse effects of documented traumatic injuries and falls were reported for 9.5% (n = 16). Four hundred forty-eight adverse effects were identified and organized into 13 broad categories representing drug-induced changes in nervous, circulatory, and muscular systems. These changes were reported for 157 medications reviewed (92.9%) and could result in fall injuries. The accompanying list of medications can serve as a ready reference for podiatric physicians and other health-care professionals when monitoring and counseling patients regarding the potential for medication-induced fall injuries, which are especially common in the elderly population.

Accidental Falls↗
PubMedDate not supplied

Revisiting epinephrine in foot surgery.

Anesthetics containing epinephrine have long been thought unsuitable for use in the foot and, particularly, the digits. However, research suggests that epinephrine use is beneficial in the appropriately selected patient. These benefits include a decreased local anesthetic plasma concentration; an increased duration of anesthesia, with a decreased need for additional narcotic use after surgery; decreased development of hemorrhage and postoperative hematoma, without occlusion of vessels; and a lack of complications (in millions of patients reported on in the literature). A retrospective review of more than 150 patients receiving local anesthetics containing epinephrine revealed no complications in the foot and ankle.

Anesthetics, Local↗