Search PubMed⌕ Search

Biomedical subjects

S B Nelson

Publications and source records attributed to S B Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1997

A quantitative description of short-term plasticity at excitatory synapses in layer 2/3 of rat primary visual cortex.

Cortical synapses exhibit several forms of short-term plasticity, but the contribution of this plasticity to visual response dynamics is unknown. In part, this is because the simple patterns of stimulation used to probe plasticity in vitro do not correspond to patterns of activity that occur in vivo. We have developed a method of quantitatively characterizing short-term plasticity at cortical synapses that permits prediction of responses to arbitrary patterns of stimulation. Synaptic responses were recorded intracellularly as EPSCs and extracellularly as local field potentials in layer 2/3 of rat primary visual cortical slices during stimulation of layer 4 with trains of electrical stimuli containing random mixtures of frequencies. Responses exhibited complex dynamics that were well described by a simple three-component model consisting of facilitation and two forms of depression, a stronger form that decayed exponentially with a time constant of several hundred milliseconds and a weaker, but more persistent, form that decayed with a time constant of several seconds. Parameters obtained from fits to one train were used to predict accurately responses to other random and constant frequency trains. Control experiments revealed that depression was not caused by a decrease in the effectiveness of extracellular stimulation or by a buildup of inhibition. Pharmacological manipulations of transmitter release and postsynaptic sensitivity suggested that both forms of depression are mediated presynaptically. These results indicate that firing evoked by visual stimuli is likely to cause significant depression at cortical synapses. Hence synaptic depression may be an important determinant of the temporal features of visual cortical responses.

Animals↗
PubMed1997

Synaptic depression and cortical gain control.

Cortical neurons receive synaptic inputs from thousands of afferents that fire action potentials at rates ranging from less than 1 hertz to more than 200 hertz. Both the number of afferents and their large dynamic range can mask changes in the spatial and temporal pattern of synaptic activity, limiting the ability of a cortical neuron to respond to its inputs. Modeling work based on experimental measurements indicates that short-term depression of intracortical synapses provides a dynamic gain-control mechanism that allows equal percentage rate changes on rapidly and slowly firing afferents to produce equal postsynaptic responses. Unlike inhibitory and adaptive mechanisms that reduce responsiveness to all inputs, synaptic depression is input-specific, leading to a dramatic increase in the sensitivity of a neuron to subtle changes in the firing patterns of its afferents.

Action Potentials↗
PubMed1995

An emergent model of orientation selectivity in cat visual cortical simple cells.

It is well known that visual cortical neurons respond vigorously to a limited range of stimulus orientations, while their primary afferent inputs, neurons in the lateral geniculate nucleus (LGN), respond well to all orientations. Mechanisms based on intracortical inhibition and/or converging thalamocortical afferents have previously been suggested to underlie the generation of cortical orientation selectivity; however, these models conflict with experimental data. Here, a 1:4 scale model of a 1700 microns by 200 microms region of layer IV of cat primary visual cortex (area 17) is presented to demonstrate that local intracortical excitation may provide the dominant source of orientation-selective input. In agreement with experiment, model cortical cells exhibit sharp orientation selectivity despite receiving strong iso-orientation inhibition, weak cross-orientation inhibition, no shunting inhibition, and weakly tuned thalamocortical excitation. Sharp tuning is provided by recurrent cortical excitation. As this tuning signal arises from the same pool of neurons that it excites, orientation selectivity in the model is shown to be an emergent property of the cortical feedback circuitry. In the model, as in experiment, sharpness of orientation tuning is independent of stimulus contrast and persists with silencing of ON-type subfields. The model also provides a unified account of intracellular and extracellular inhibitory blockade experiments that had previously appeared to conflict over the role of inhibition. It is suggested that intracortical inhibition acts nonspecifically and indirectly to maintain the selectivity of individual neurons by balancing strong intracortical excitation at the columnar level.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

NMDA receptors in sensory information processing.

During the past year electrophysiological studies, particularly in the visual and somatosensory systems, have begun to uncover the specific roles played by NMDA receptors in the processing of sensory information. Many of the features of NMDA-receptor-mediated sensory responses reflect known properties of the receptor.

Afferent Pathways↗
PubMed1992

Effect of stimulus contrast and size on NMDA receptor activity in cat lateral geniculate nucleus.

1. We studied the effect of varying excitatory and inhibitory drive on the N-methyl-D-aspartate (NMDA) receptor-mediated component of the visual responses of neurons in the cat dorsal lateral geniculate nucleus (dLGN) by varying the contrast and size of stimuli presented to the receptive fields of these cells. 2. Cells were classified as either on- or off-center, X or Y, and lagged or nonlagged. Stimulus contrast, and hence the amount of excitatory drive, was varied by changing the brightness of a spot, whose size and location matched the cell's receptive field center, relative to a fixed background luminance. Responses to varying contrast were collected from each cell before, during, and after iontophoretic application of D-2-amino-5-phosphonovaleric acid (D-APV), a specific NMDA receptor antagonist. From each contrast-response plot, a sigmoidal curve fit yielded five parameters on which we examined the effect of D-APV: the threshold contrast, saturation contrast, contrast at half saturation (C50), slope (gain) at C50, and saturation response. 3. In most cells, application of D-APV reduced both the saturation response and the gain of the contrast-response curve, but did not reduce or change significantly the threshold contrast, saturation contrast, or C50. 4. Cells varied in their sensitivity to D-APV, but for any given cell, the D-APV-sensitive component was nearly always a linear function of the control visual response level. Thus, for a spot of optimal size, there was a constant proportion of the visual response attributable to NMDA receptors, regardless of the amplitude of the response. 5. When the effect of D-APV on the visual responses to an optimal spot at varying contrasts was compared among different classes of dLGN cells, the visual responses of lagged X cells were reduced to a greater extent than those of either nonlagged X cells or the combined population of nonlagged X and Y cells. 6. Stimulus size (spot diameter) was also varied systematically at a fixed contrast to vary the inhibitory drive to dLGN cells. As stimulus size was increased, the response first increased because of increased stimulation of the receptive field center and then decreased because of increasing amounts of surround inhibition. 7. The D-APV-sensitive component of individual cell responses was greater when the stimulus spot was less than or equal to optimal size than when the spot was larger. Thus the contribution of NMDA receptors to the visual response decreased with increasing surround inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

College vs junior high school students' knowledge of alcohol as a teratogen.

This study assessed knowledge possessed by male and female junior high school and college students (N = 422) about the teratogenic effects of alcohol. Although most students were aware that alcohol is a teratogenic substance, they demonstrated little knowledge of the nature and timing of possible specific negative effects.

Adolescent↗
PubMed1991

Oxygen-induced hypercarbia in obstructive pulmonary disease.

We investigated the mechanisms responsible for oxygen-induced hypercarbia in ventilator-dependent patients with advanced chronic obstructive pulmonary disease (COPD). To quantitate the effects of oxygen (O2) on respiratory drive, we determined the CO2 recruitment threshold (PCO2 RT) in 10 mechanically ventilated patients under normoxic (PaO2 = 67 +/- 7 mm Hg) and hyperoxic (PaO2 = 370 +/- 67 mm Hg) conditions. PCO2 RT is a measure of the CO2 responsiveness of the mechanically unloaded respiratory system and, as such, is independent of mechanical impedance and respiratory muscle strength. After O2 supplementation, PCO2 RT increased from 42 +/- 6 to 45 +/- 6 mm Hg (p less than or equal to 0.05), indicating a suppression of so-called hypoxic respiratory drive. The effect of hyperoxia on the dead space to tidal volume ratio (VD/VT) and CO2 elimination (VCO2) was studied in 6 patients. Measurements were made at identical ventilator settings, thus eliminating breathing pattern- and respiratory work-related effects on these variables. VD/VT rose from 0.49 +/- 0.09 to 0.55 +/- 0.06 (p less than or equal to 0.05), but VCO2 remained constant at 0.21 L/min. We discuss why measuring O2-induced changes in minute ventilation, VCO2, PaO2, and VD/VT in spontaneously breathing patients is insufficient to distinguish between gas exchange- and respiratory drive-related mechanisms for hypercarbia. Based on the O2-induced increase in PCO2 RT, we conclude that so-called suppression of hypoxic drive plays an important role in the pathogenesis of this disorder.

Aged↗
PubMed1991

Influence of sleep state on CO2 responsiveness. A study of the unloaded respiratory pump in humans.

We measured the ventilatory recruitment threshold for CO2 (RT) during wakefulness, nonrapid eye movement sleep (NREM), and rapid eye movement sleep (REM) in eight patients with respiratory failure. Because the lungs were mechanically ventilated during the RT measurements, we were able to define the effects of arousal state on the chemoresponsiveness of the unloaded respiratory system. Ventilator settings were held constant in each patient, assuring that mechanoreceptor input to the respiratory controller remained the same during all measurements. RT increased from 38 +/- 6 mm Hg during relaxed wakefulness to 42 +/- 8 mm Hg during NREM sleep (p less than or equal to 0.01), consistent with a blunting of chemoresponsiveness during sleep. In five subjects we were able to measure RT during REM sleep also. In four of them, REM RT exceeded the wakefulness measurement by at least 3 mm Hg. The remaining patient showed no demonstrable changes in RT during either sleep state. We conclude that the loss of a wakefulness stimulus contributes to sleep-induced hypercarbia in humans.

Adult↗
PubMed1991

The control of breathing during weaning from mechanical ventilation.

Using the recruitment threshold technique, we measured the CO2 responsiveness of the unloaded respiratory pump in 14 mechanically ventilated patients prior to weaning. The CO2 recruitment threshold (CO2RT) was compared with the arterial CO2 tension during unassisted breathing (CO2SB) and with the PaCO2 during mechanical ventilation (CO2MV) at machine settings determined by the primary physician. Based on these comparisons, we tested the hypotheses that (1) patients without weaning-induced respiratory distress (group 1) maintain CO2SB near CO2RT, (2) patients with weaning-induced respiratory distress (group 2) retain CO2SB above CO2RT, thereby manifesting incomplete load compensation, and (3) CO2MV is ventilator setting dependent and provides insufficient information about the ventilatory requirement during weaning. Respiratory distress was prospectively defined as sustained tachypnea (rate greater than or equal to 30) or intense dyspnea (Borg scale rating) and limited weaning in nine of 14 patients. The average CO2RT was 40 mm Hg in both groups. All patients in group 1 maintained CO2SB near CO2RT (p greater than 0.1). Seven of nine patients in group 2 retained CO2 by greater than or equal to 3 mm Hg above CO2RT (p less than 0.01). There was no significant difference between CO2MV and CO2SB in either group. We conclude that CO2RT provides a better reference of the adequacy of ventilatory load compensation during weather than CO2MV.

Aged↗
PubMed1991

Metered dose inhalers for bronchodilator delivery in intubated, mechanically ventilated patients.

We determined the relative efficacy of two bronchodilator aerosol delivery methods in 18 intubated mechanically ventilated patients with airways obstruction. Two treatment arms, consisting of albuterol 270 micrograms (three puffs) from a metered dose inhaler and albuterol 2.5 mg from a saline solution nebulized with an updraft inhaler, were compared in a single blind, randomized crossover design. Pulmonary function was evaluated using an interrupter technique. Changes in passive expiratory flow at respiratory system recoil pressures between 6 and 10 cm H2O provided the therapeutic endpoints. Paired measurements were made before and 30 minutes after drug delivery. The MDI and NEB resulted in similar improvements in iso-recoil flow (mean increase for both groups = 0.1 L/s). Treatment sequence, severity of obstruction, and bronchodilator responsiveness had no effect on relative efficacy. Albuterol caused a small but significant increase in heart rate that was similar following both delivery methods. We conclude that bronchodilator aerosol delivery with metered dose inhalers provides a viable alternative to nebulizer therapy in intubated mechanically ventilated patients and may result in a cost savings to hospitals and patients.

Aerosols↗
PubMed1991

Temporal interactions in the cat visual system. I. Orientation-selective suppression in the visual cortex.

The perception of a visual contour depends on the spatial and temporal context in which it is viewed. Interactions between visual contours are believed to underlie a wide range of perceptual phenomena, including geometric illusions and aftereffects, contrast adaptation, and visual masking. The physiological mechanisms that might underlie such interactions were studied in the visual cortex of the cat by recording responses of single neurons to pairs of brief stationary stimuli that were separated in time. The results revealed a long-lasting, orientation-selective suppression, termed "paired-pulse suppression," which was strongest at the cell's preferred orientation, but which was more broadly tuned for orientation than the excitatory response of the cell. Although the strength and duration of the suppression varied widely, some degree of response reduction was present in most cells studied. The function of this suppression may be to regulate the gain with which visual inputs are transmitted to cortical neurons, thus preventing response saturation and positive feedback.

Anesthesia↗
PubMed1991

Temporal interactions in the cat visual system. II. Suppressive and facilitatory effects in the lateral geniculate nucleus.

Extracellular responses were recorded from single neurons in the lateral geniculate nucleus (LGN) of the cat during presentation of pairs of brief visual stimuli identical to those that produce orientation-selective paired-pulsed suppression in the visual cortex. LGN neurons also show paired-pulse suppression, but the suppression is not orientation selective, and it occurs only for short interstimulus intervals (ISIs; usually less than 200 msec). At longer ISIs, most LGN neurons show a period of facilitation. Thus, the paired-pulse suppression in the LGN cannot account for that seen in the visual cortex. Paired-pulse suppression in the LGN was found to be enhanced by stimulation of the receptive field surround. LGN neurons also showed a second type of suppression, termed "offset suppression," which consisted of a more long-lasting suppression of spontaneous activity following the offset of an excitatory visual stimulus. The suppression of spontaneous activity was accompanied by a reduction of the antidromic excitability, assessed by stimulating LGN axons within the cortex or optic radiation. Unlike paired-pulsed suppression, offset suppression was not enhanced by increased stimulation of the receptive field surround. Paired-pulse suppression and offset suppression are most likely due to different mechanisms because they have different time courses and depend differently on the spatial properties of the stimuli. Functionally, paired-pulse suppression may be related to the reduced visual sensitivity that accompanies eye movements, while offset suppression may serve to enhance temporal contrast.

Animals↗
PubMed1991

Temporal interactions in the cat visual system. III. Pharmacological studies of cortical suppression suggest a presynaptic mechanism.

When tested with pairs of brief visual stimuli, neurons of the primary visual cortex of the cat show a long-lasting, orientation-selective suppression, termed "paired-pulse suppression." The hypothesis that this suppression is due to GABAA-mediated inhibition was tested by performing temporal interaction tests before, during, and after iontophoretic application of the selective antagonist bicuculline methiodide (BMI). In keeping with previous reports, BMI elevated the spontaneous and evoked firing rates of cortical neurons, and altered basic receptive field properties. Under the influence of BMI, most neurons showed a reduced or abolished selectivity for stimulus orientation and direction of movement. The effects on orientation selectivity required higher ejection currents than did the effects on directional selectivity. At high ejection currents, most cells did lose selectivity for the orientation of a moving stimulus, but retained some selectivity for the orientation of a stationary stimulus. BMI, even at very high ejection currents, did not abolish paired-pulse suppression. In some cells, BMI enhanced or prolonged paired-pulse suppression. In further experiments, temporal interaction tests were performed in which one or the other of the component stimuli was replaced with a pharmacological stimulus (a pulse of glutamate or potassium). A pharmacological stimulus did not produce suppression of the response to a subsequent visual stimulus, nor did a visual stimulus suppress the response to a subsequent pharmacological stimulus. Paired-pulse suppression occurred only when both stimuli were visual. Taken together with previous results, the present data indicate that paired-pulse suppression is most likely due to a presynaptic mechanism.

Animals↗
PubMed1990

The ventilatory recruitment threshold for carbon dioxide.

We report our initial experience with a technique with which the chemoresponsiveness of the respiratory controller can be characterized in terms of an inspiratory on-switch threshold to CO2. After suppression of phasic respiratory muscle activity by mechanical ventilation, a CO2 recruitment threshold (PCO2RT) was defined as the lowest alveolar CO2 tension at which CO2 supplementation to inspired gas caused a reappearance of inspiratory efforts. Because PCO2RT can be determined in the absence of a mechanical load on the ventilatory pump, respiratory system mechanics and inspiratory muscle function should not influence the measurement itself. Thus, this technique may be helpful to study ventilatory requirements and load responses in critically ill patients with respiratory failure. We have shown that inspiratory muscle recruitment can be equally well-inferred from changes in the airway pressure and flow tracings during mechanical ventilation, from the pattern of chest wall displacement, and from the integrated diaphragm electromyogram. Within a subject, PCO2RT is a reproducible measurement that is not influenced by ventilator settings and end-expiratory lung volume, provided that phasic respiratory muscle has been suppressed prior to CO2 supplementation. Details of the methodology, the likely determinants of PCO2RT, and the clinical utility of this technique are discussed.

Adult↗
PubMed1990

Performance evaluation of contemporary spirometers.

A comprehensive evaluation of 62 spirometers from 37 different sources was performed using a two-part protocol: calibrated syringe, and dynamic waveform testing. All testing was done with ambient air. Calibrated syringe testing examined the ability of the spirometers to accurately measure the output of a 3 L calibrating syringe under varying conditions. The accuracy, FVC volume linearity, and stability of each spirometer was determined from these data. All but five of 42 spirometers accurately measured a 3 L calibrating syringe to within +/- 3 percent. Dynamic waveform testing consisted of introducing 24 standard waveforms into the spirometer from a computer-controlled air pump. The values of FVC, FEV1, and FEF25-75% were compared to the actual values for each waveform to determine a performance rating. Only 35 (56.5 percent) of the spirometers performed acceptably when measuring the 24 standard waveforms. Nine (14.5 percent) were marginal and 18 (29.0 percent) were unacceptable. Fifty-nine (95 percent) of the 62 spirometers were computerized. Software errors were found in 25 percent of the computerized systems evaluated. Although using a 3 L syringe for quality control purposes is essential, simple testing of spirometers with a 3 L calibrating syringe for validation purposes was inadequate to assess spirometer performance when compared to dynamic waveform testing. Dynamic waveform testing is essential to accurately measure and validate acceptability of spirometer system performance.

Calibration↗
PubMed1990

The assessment of major airway function in a ventilator-dependent patient with tracheomalacia.

A 60-pack-year smoker presented with cough, dyspnea and orthopnea of three months' duration. Spirometry revealed severe reduction in maximal expiratory flow; CT of the chest and bronchoscopy demonstrated expiratory collapse of a mid-tracheal segment, and a presumptive diagnosis of tracheomalacia was made. A right lateral thoracotomy was performed to resect the unstable segment and improve maximal expiratory flow. Diffuse major airway disease with absence of cartilaginous rings from the thoracic inlet to the mainstem bronchi was encountered. The trachea and mainstem bronchi were stented externally. A high resistance to airflow and absence of expiratory flow limitation were present, suggesting a fixed rather than variable intrathoracic obstruction of major airways. This case illustrates some potential pitfalls in preoperative assessment of patients with tracheomalacia. Recordings of airway pressure and flow during mechanical ventilation are useful in distinguishing between fixed and variable intrathoracic obstruction and may complement tests of airway anatomy.

Airway Resistance↗