bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of macrophages in virus-induced airway hyperresponsiveness and neuronal M2muscarinic receptor dysfunction
Authors: Lee Ann M. , Fryer Allison D. , van Rooijen Nico , Jacoby David B.
Published: May 2004

Viral infections exacerbate asthma. One of the pathways by which viruses trigger bronchoconstriction and hyperresponsiveness is by causing dysfunction of inhibitory M2muscarinic receptors on the airway parasympathetic nerves. These receptors normally limit acetylcholine (ACh) release from the parasympathetic nerves. Loss of M2receptor function increases ACh release, thereby increasing vagally mediated bronchoconstriction. Because viral infection causes an influx of macrophages into the lungs, we tested the role of macrophages in virus-induced airway hyperresponsiveness and M2receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperresponsive to electrical stimulation of the vagus nerves but not to intravenous ACh, indicating that hyperresponsiveness was due to increased release of ACh from the nerves. In addition, the muscarinic agonist pilocarpine no longer inhibited vagally induced bronchoconstriction, indicating M2receptor dysfunction. Treating animals with liposome-encapsulated dichloromethylene-diphosphonate depleted macrophages as assessed histologically. In these animals, viral infection did not cause airway hyperresponsiveness or M2receptor dysfunction. These data suggest that macrophages mediate virus-induced M2receptor dysfunction and airway hyperresponsiveness.
AT1A-mediated activation of kidney JNK1 and SMAD2 in obstructive uropathy: preservation of kidney tissue mass using candesartan
Authors: Wamsley-Davis Ann , Padda Ranjit , Truong Luan D. , Tsao Chun Chui , Zhang Ping , Sheikh-Hamad David
Published: May 2004

Literature suggests the involvement of the renin-angiotensin system and transforming growth factor (TGF)-β in the renal injury that follows chronic ureteric obstruction. SMAD proteins and the JNK1 cascade are essential components of TGF-β signaling machinery, and recent data suggest cooperative interaction between JNK1 and SMAD proteins in TGF-β-mediated gene expression. We used a rat model of chronic unilateral ureteric obstruction to study the effects of candesartan, an AT1A-receptor blocker, on tissue morphology and the activities of JNK1 and SMAD2 protein in the kidney. Ureteric obstruction for 28 days leads to interstitial fibrosis, tubule atrophy, and marked activation of SMAD2 and JNK1, without significant change in p38 kinase or ERK. Candesartan treatment, however, attenuated the chronic tubulointerstitial injury in obstructed kidneys and was associated with significant preservation of kidney tissue mass. Furthermore, treatment with candesartan diminished JNK1 activity and downregulated SMAD2 protein and activity in obstructed kidneys. In conclusion, obstructed kidneys showed chronic tubulointerstitial injury, which was associated with JNK1 and SMAD2 activation. The renoprotective effects afforded by AT1A-receptor blockade in obstructive uropathy are consistent with attenuation of JNK1- and SMAD2-mediated renal injury.
Associations between physical activity and bone mass in black and white South African children at age 9 yr
Authors: McVeigh J. A. , Norris S. A. , Cameron N. , Pettifor J. M.
Published: May 2004

We investigated differences in physical activity (PA) levels between black and white South African 9-yr-old children and their association with bone mineral content (BMC) and density (BMD) by using dual-energy X-ray absorptiometry. PA was analyzed in terms of a metabolic (METPA; weighted metabolic score of intensity, frequency, and duration) and a mechanical (MECHPA; sum of all ground reaction forces multiplied by duration) component. There were significant ethnic differences in patterns of activity. White children expended a significantly greater energy score (METPA of 21.7 ± 2.9) than black children (METPA of 9.5 ± 0.5) ( P < 0.001). When children were divided into quartiles according to the amount and intensity of sport played, the most active white children (using METPA scores) had significantly higher whole body BMD and higher hip and spine BMC and BMD than less active children. White children in the highest MECHPA quartile also showed significantly higher whole body, hip, and spine BMC and BMD than those children in the lowest quartile. No association between exercise and bone mass of black children was found. In this population, PA has an osteogenic association with white children, but not black children, which may be explained by the lower levels of PA in the black children. Despite this, black children had significantly greater bone mass at the hip and spine (girls only) ( P < 0.001) even after adjustment for body size. The role of exercise in increasing bone mass may become increasingly critical as a protective mechanism against osteoporosis in both ethnic groups, especially because the genetic benefit exhibited by black children to higher bone mass may be weakened with time, as environmental influences become stronger.
Correspondence between laryngeal vocal fold movement and muscle activity during speech and nonspeech gestures
Authors: Poletto Christopher J. , Verdun Laura P. , Strominger Robert , Ludlow Christy L.
Published: May 2004

To better understand the role of each of the laryngeal muscles in producing vocal fold movement, activation of these muscles was correlated with laryngeal movement during different tasks such as sniff, cough or throat clear, and speech syllable production. Four muscles [the posterior cricoarytenoid, lateral cricoarytenoid, cricothyroid (CT), and thyroarytenoid (TA)] were recorded with bipolar hooked wire electrodes placed bilaterally in four normal subjects. A nasoendoscope was used to record vocal fold movement while simultaneously recording muscle activity. Muscle activation level was correlated with ipsilateral vocal fold angle for vocal fold opening and closing. Pearson correlation coefficients and their statistical significance were computed for each trial. Significant effects of muscle ( P ≤ 0.0005) and task ( P = 0.034) were found on the r (transformed to Fisher's Z′) values. All of the posterior cricoarytenoid recordings related significantly with vocal opening, whereas CT activity was significantly correlated with opening only during sniff. The TA and lateral cricoarytenoid activities were significantly correlated with vocal fold closing during cough. During speech, the CT and TA activity correlated with both opening and closing. Laryngeal muscle patterning to produce vocal fold movement differed across tasks; reciprocal muscle activity only occurred on cough, whereas speech and sniff often involved simultaneous contraction of muscle antagonists. In conclusion, different combinations of muscle activation are used for biomechanical control of vocal fold opening and closing movements during respiratory, airway protection, and speech tasks.
Improved Spike-Sorting By Modeling Firing Statistics and Burst-Dependent Spike Amplitude Attenuation: A Markov Chain Monte Carlo Approach
Authors: Pouzat Christophe , Delescluse Matthieu , Viot Pascal , Diebolt Jean
Published: May 2004

Spike-sorting techniques attempt to classify a series of noisy electrical waveforms according to the identity of the neurons that generated them. Existing techniques perform this classification ignoring several properties of actual neurons that can ultimately improve classification performance. In this study, we propose a more realistic spike train generation model. It incorporates both a description of “nontrivial” (i.e., non-Poisson) neuronal discharge statistics and a description of spike waveform dynamics (e.g., the events amplitude decays for short interspike intervals). We show that this spike train generation model is analogous to a one-dimensional Potts spin-glass model. We can therefore tailor to our particular case the computational methods that have been developed in fields where Potts models are extensively used, including statistical physics and image restoration. These methods are based on the construction of a Markov chain in the space of model parameters and spike train configurations, where a configuration is defined by specifying a neuron of origin for each spike. This Markov chain is built such that its unique stationary density is the posterior density of model parameters and configurations given the observed data. A Monte Carlo simulation of the Markov chain is then used to estimate the posterior density. We illustrate the way to build the transition matrix of the Markov chain with a simple, but realistic, model for data generation. We use simulated data to illustrate the performance of the method and to show that this approach can easily cope with neurons firing doublets of spikes and/or generating spikes with highly dynamic waveforms. The method cannot automatically find the “correct” number of neurons in the data. User input is required for this important problem and we illustrate how this can be done. We finally discuss further developments of the method.
FMRI Measurement of CNS Responses to Naloxone Infusion and Subsequent Mild Noxious Thermal Stimuli in Healthy Volunteers
Authors: Borras M. C. , Becerra L. , Ploghaus A. , Gostic J. M. , DaSilva A. , Gonzalez R. G. , Borsook D.
Published: May 2004

The aims of this study were to assess the effects of a μ-opioid antagonist, naloxone, on endogenous opioid systems and to evaluate the effect of naloxone on the CNS response to mild noxious heat. Doubled-blinded experiments were performed in a cross-over design in 10 healthy male volunteers. Functional magnetic resonance imaging (fMRI) data were collected before and during the infusion and also during thermal stimuli. Increased signal was observed in a number of cortical and subcortical brain regions for naloxone versus saline infusion. Cortical activation was induced in regions including cingulate, prefrontal cortex, and insula. Subcortical regions showing increased signal change included hippocampus and entorhinal cortex. A 46°C stimulus delivered to the back of the hand induced an overall increase in activation in a number of regions in the naloxone group that were not seen in the saline group (e.g., insula, orbitofrontal cortex, thalamus, and hippocampus). These results show that naloxone, even in the absence of psychophysical effects, produces activation in several brain regions that are known to have high levels of μ-opioid receptors and may be involved in endogenous analgesia. Our study is an example of how fMRI can measure subtle changes in brain activation induced by pharmacological agents without cognitive effects.
On the Relation Between Object Shape and Grasping Kinematics
Authors: Cuijpers Raymond H. , Smeets Jeroen B. J. , Brenner Eli
Published: May 2004

Despite the many studies on the visual control of grasping, little is known about how and when small variations in shape affect grasping kinematics. In the present study we asked subjects to grasp elliptical cylinders that were placed 30 and 60 cm in front of them. The cylinders' aspect ratio was varied systematically between 0.4 and 1.6, and their orientation was varied in steps of 30°. Subjects picked up all noncircular cylinders with a hand orientation that approximately coincided with one of the principal axes. The probability of selecting a given principal axis was the highest when its orientation was equal to the preferred orientation for picking up a circular cylinder at the same location. The maximum grip aperture was scaled to the length of the selected principal axis, but the maximum grip aperture was also larger when the length of the axis orthogonal to the grip axis was longer than that of the grip axis. The correlation between the grip aperture— or the hand orientation—at a given instant, and its final value, increased monotonically with the traversed distance. The final hand orientation could already be inferred from its value after 30% of the movement distance with a reliability that explains 50% of the variance. For the final grip aperture, this was only so after 80% of the movement distance. The results indicate that the perceived shape of the cylinder is used for selecting appropriate grasping locations before or early in the movement and that the grip aperture and orientation are gradually attuned to these locations during the movement.
Analysis of the Optimal Channel Density of the Squid Giant Axon Using a Reparameterized Hodgkin–Huxley Model
Authors: Sangrey Thomas D. , Friesen W. Otto , Levy William B
Published: May 2004

A reparameterized Hodgkin–Huxley-type model is developed that improves the 1952 model's fit to the biological action potential. In addition to altering Na+inactivation and K+activation kinetics, a voltage-dependent gating-current mechanism has been added to the model. The resulting improved model fits the experimental trace nearly exactly over the rising phase, and it has a propagation velocity that is within 3% of the experimentally measured value of 21.2 m/s (at 18.5°C). Having eliminated most inaccuracies associated with the velocity-dependent rising phase of the action potential, the model is used to test Hodgkin's maximum velocity hypothesis, which asserts that channel density has evolved to maximize conduction velocity. In fact the predicted optimal channel density is more than twice as high as the actual squid channel density. When the available capacitance is reduced to approximate more modern serial Na+-channel models, the optimal channel density is 4 times the actual value. We suggest that, although Hodgkin's maximum velocity hypothesis is acceptable as a first approximation, the microscopic optimization perspective of natural selection will not explain the channel density of the squid unless other constraints are taken into account, for example, the metabolic costs of velocity.
Independent Components of Color Natural Scenes Resemble V1 Neurons in Their Spatial and Color Tuning
Authors: Caywood Matthew S. , Willmore Benjamin , Tolhurst David J.
Published: May 2004

It has been hypothesized that mammalian sensory systems are efficient because they reduce the redundancy of natural sensory input. If correct, this theory could unify our understanding of sensory coding; here, we test its predictions for color coding in the primate primary visual cortex (V1). We apply independent component analysis (ICA) to simulated cone responses to natural scenes, obtaining a set of colored independent component (IC) filters that form a redundancy-reducing visual code. We compare IC filters with physiologically measured V1 neurons, and find great spatial similarity between IC filters and V1 simple cells. On cursory inspection, there is little chromatic similarity; however, we find that many apparent differences result from biases in the physiological measurements and ICA analysis. After correcting these biases, we find that the chromatic tuning of IC filters does indeed resemble the population of V1 neurons, supporting the redundancy-reduction hypothesis.
Processing of Band-Passed Noise in the Lateral Auditory Belt Cortex of the Rhesus Monkey
Authors: Rauschecker Josef P. , Tian Biao
Published: May 2004

Neurons in the lateral belt areas of rhesus monkey auditory cortex were stimulated with band-passed noise (BPN) bursts of different bandwidths and center frequencies. Most neurons responded much more vigorously to these sounds than to tone bursts of a single frequency, and it thus became possible to elicit a clear response in 85% of lateral belt neurons. Tuning to center frequency and bandwidth of the BPN bursts was analyzed. Best center frequency varied along the rostrocaudal direction, with 2 reversals defining borders between areas. We confirmed the existence of 2 belt areas (AL and ML) that were laterally adjacent to the core areas (R and A1, respectively) and a third area (CL) adjacent to area CM on the supratemporal plane (STP). All 3 lateral belt areas were cochleotopically organized with their frequency gradients collinear to those of the adjacent STP areas. Although A1 neurons responded best to pure tones and their responses decreased with increasing bandwidth, 63% of the lateral belt neurons were tuned to bandwidths between 1/3 and 2 octaves and showed either one or multiple peaks. The results are compared with previous data from visual cortex and are discussed in the context of spectral integration, whereby the lateral belt forms a relatively early stage of processing in the cortical hierarchy, giving rise to parallel streams for the identification of auditory objects and their localization in space.
Theta Rhythmic Stimulation of Stratum Lacunosum-Moleculare in Rat Hippocampus Contributes to Associative LTP at a Phase Offset in Stratum Radiatum
Authors: Judge Sarah J. , Hasselmo Michael E.
Published: May 2004

Computational modeling demonstrates that encoding and context-dependent retrieval of memories in region CA1 of the hippocampus will be most effective when the phase of strongest entorhinal input (to stratum lacunosum-moleculare) is offset from the phase of maximal induction of long-term potentiation at Schaffer collateral synapses (in s. radiatum). This would allow entorhinal input to play a role in both retrieval and encoding without engaging long-term potentiation (LTP) during retrieval. Experiments in brain slice preparations of the hippocampal formation tested the relationship between rhythmic input to s. lacunosum-moleculare and the time of maximal LTP induction at Schaffer collateral synapses in s. radiatum. Analysis of the data demonstrates a statistically significant difference in the induction of LTP for different time intervals between the end of each four-pulse train in s. lacunosum-moleculare and the single pulse s. radiatum stimulation. The time of maximal LTP induction was found to be ∼30 ms after the end of lacunosum-moleculare stimulation, consistent with the requirements of the model.
Cortical Involvement in the Recruitment of Wrist Muscles
Authors: Shah Ashvin , Fagg Andrew H. , Barto Andrew G.
Published: May 2004

In executing a voluntary movement, one is faced with the problem of translating a specification of the movement in task space (e.g., a visual goal) into a muscle-recruitment pattern. Among many brain regions, the primary motor cortex (MI) plays a prominent role in the specification of movements. In what coordinate frame MI represents movement has been a topic of considerable debate. In a two-dimensional wrist step-tracking experiment, Kakei et al. described some MI cells as encoding movement in a muscle-coordinate frame and other cells as encoding movement in an extrinsic-coordinate frame. This result was interpreted as evidence for a cascade of transformations within MI from an extrinsic representation of movement to a muscle-like representation. However, we present a model that demonstrates that, given a realistic extrinsic-like representation of movement, a simple linear network is capable of representing the transformation from an extrinsic space to the muscle-recruitment patterns implementing the movements on which Kakei et al. focused. This suggests that cells exhibiting extrinsic-like qualities can be involved in the direct recruitment of spinal motor neurons. These results call into question models that presume a serial cascade of transformations terminating with MI pyramidal tract neurons that vary their activation exclusively with muscle activity. Further analysis of the model shows that the correlation between the activity of an MI neuron and a muscle does not predict the strength of the connection between the MI neuron and muscle. This result cautions against the use of correlation methods as a measure of cellular connectivity.
Area-Selective Neuronal Activity in the Dorsolateral Prefrontal Cortex for Information Retrieval and Action Planning
Authors: Hoshi Eiji , Tanji Jun
Published: May 2004

We compared how neurons in the dorsal and ventral regions of the dorsolateral prefrontal cortex (dl-PFC) participate in processing 2 sets of sensory signals, given at intervals, to generate plans for future actions. For the first set of visual signals, neurons in the ventral region of dl-PFC responded preferentially to the visuospatial properties of the signal, whereas neurons in the dorsal region of dl-PFC were involved primarily in retrieving information from the signal, such as the location of the target or which arm to use. For the second set of visual signals, most ventral dl-PFC neurons reflected either the sensory properties of the signals or the information retrieved from each signal. By contrast, dorsal neurons were involved more in integrating information about the target location and which arm to use to reach the target, thereby generating information that could be used to plan future actions. Thus sensorimotor transformations in the dorsolateral PFC appear to be time-variant and region-selective.
Cutaneous Painful Laser Stimuli Evoke Responses Recorded Directly From Primary Somatosensory Cortex in Awake Humans
Authors: Ohara S. , Crone N. E. , Weiss N. , Treede R.-D. , Lenz F. A.
Published: May 2004

Negative and positive laser evoked potential (LEP) peaks (N2*, P2**) were simultaneously recorded from the primary somatosensory (SI), parasylvian, and medial frontal (MF: anterior cingulate and supplementary motor area) cortical surfaces through subdural electrodes implanted for the surgical treatment of intractable epilepsy. Distribution of the LEP N2*and P2**peaks was estimated to be in cortical areas (SI, parasylvian, and MF) identified by anatomic criteria, by their response to innocuous vibratory stimulation of a finger (v-SEP), and to electrical stimulation of the median nerve (e-SEP). The maximum of the LEP N2*peak was located on the CS, medial (dorsal) to the finger motor area, as determined by cortical stimulation, and to the finger somatosensory area, as determined from the e-SEP and v-SEP. This finding suggests that the generator source of the LEP N2*peak in SI was different from that of e-SEP or v-SEP in Brodmann's areas 3b or 1. In parasylvian and MF, polarity reversal was often observed, indicating tangential current sources in these regions. In contrast to e-SEP and v-SEP, the LEP N2*latency over SI was not shorter than that over the parasylvian region. The amplitude of N2*was larger over SI than over MF and the latencies of the LEP peaks in those 2 regions were different. These findings provide evidence for a significant LEP generator in the postcentral gyrus, perhaps SI cortex, that is situated outside the tactile homunculus in SI and that receives its input arising from nociceptors simultaneously with parasylvian and MF cortex.
Frequency-Dependent Processing in the Vibrissa Sensory System
Authors: Moore Christopher I.
Published: May 2004

The vibrissa sensory system is a key model for investigating principles of sensory processing. Specific frequency ranges of vibrissa motion, generated by rodent sensory behaviors (e.g., active exploration or resting) and by stimulus features, characterize perception by this system. During active exploration, rats typically sweep their vibrissae at ∼4–12 Hz against and over tactual surfaces, and during rest or quiescence, their vibrissae are typically still (<1 Hz). When a vibrissa is swept over an object, microgeometric surface features (e.g., grains on sandpaper) likely create higher frequency vibrissa vibrations that are greater than or equal to several hundred Hertz. In this article, I first review thalamic and cortical neural responses to vibrissa stimulation at 1–40 Hz. I then propose that neural dynamics optimize the detection of stimuli in low-frequency contexts (e.g., 1 Hz) and the discrimination of stimuli in the whisking frequency range. In the third section, I describe how the intrinsic biomechanical properties of vibrissae, their ability to resonate when stimulated at specific frequencies, may promote detection and discrimination of high-frequency inputs, including textured surfaces. In the final section, I hypothesize that distinct low- and high-frequency processing modes may exist in the somatosensory cortex (SI), such that neural responses to stimuli at 1–40 Hz do not necessarily predict responses to higher frequency inputs. In total, these studies show that several frequency-specific mechanisms impact information transmission in the vibrissa sensory system and suggest that these properties play a crucial role in perception.
Stochastic Resonance in Muscle Receptors
Authors: Fallon James B. , Carr Richard W. , Morgan David L.
Published: May 2004

Noise is generally considered to have deleterious effects on the sensitivity of a signal detection system. There are, however, several mechanisms whereby the addition of noise to the input of a system can in fact improve sensitivity. One such mechanism is stochastic resonance. Although first proposed in 1981, conclusive experimental evidence for “fully tuneable stochastic resonance” in biological systems has not previously been reported. Evidence of fully tuneable stochastic resonance in the response of afferents from Golgi tendon organs and the primary and secondary endings of muscle spindles to imposed muscle length changes is presented.
Ethanol Alters the Frequency, Amplitude, and Decay Kinetics of Sr2+-Supported, Asynchronous NMDAR mEPSCs in Rat Hippocampal Slices
Authors: Hendricson Adam W. , Sibbald John R. , Morrisett Richard A.
Published: May 2004

To discriminate between pre- and postsynaptic effects of ethanol on N-methyl-d-aspartate receptor (NMDAR) signaling in hippocampus, we adapted the technique of Sr2+ substitution to the hippocampal blind slice patch-clamp preparation. Hippocampal slices were isolated from 12- to 20-day-old rats that were killed in accordance with University of Texas Institutional Animal Care and Use Committee guidelines. NMDAR miniature excitatory postsynaptic currents (mEPSCs) were evoked from CA1 pyramidal neurons in the presence of Sr2+ (4 mM), causing the synchronous EPSC observed in the presence of Ca2+ to be supplanted by asynchronous mEPSCs. Amplitudes typically ranged from 5 to 40 pA and responded to the NMDAR antagonist (DL)-APV (50 μM), with a statistically significant reduction in mean amplitude. Ethanol (25, 50, and 75 mM) exerted dose-dependent effects on mEPSC amplitude and frequency. Peak amplitude inhibition was observed at 75 mM ethanol. Notably, ethanol significantly decreased event frequency at 50 and 75 mM ethanol. Ethanol (75 mM) also significantly increased the paired-pulse ratio of NMDAR EPSCs. Cumulative comparisons of decay time constants derived from single-exponential fitting of mEPSCs revealed significantly accelerated current decay kinetics in the presence of 75 mM ethanol. Taken together, these reductions in miniature event frequency and amplitude, concurrent with an increased rate of decay, suggest that the acute effects of ethanol on NMDAR signaling at hippocampal synapses are multifocal in nature. This finding of pre- and postsynaptic effects of ethanol on NMDAR signal strength in a brain region central to cognition is wholly consistent with previous reports of ethanol inhibition of NMDAR–long-term potentiation in vitro and with the profound cognitive deficits associated with binge-level intoxication in vivo.
Gaze-Related Response Properties of DLPN and NRTP Neurons in the Rhesus Macaque
Authors: Ono Seiji , Das Vallabh E. , Mustari Michael J.
Published: May 2004

The dorsolateral pontine nucleus (DLPN) and nucleus reticularis tegmenti pontis (NRTP) are basilar pontine nuclei important for control of eye movements. The aim of this study was to compare the response properties of neurons in DLPN and rostral NRTP (rNRTP) during visual, oculomotor, and vestibular testing. We tested 51 DLPN neurons that were modulated during smooth pursuit (23/51) or during motion of a large-field visual stimulus (28/51). Following vestibular testing, we found that the majority of smooth pursuit–related neurons in DLPN were best classified as gaze (13/23) or eye velocity (7/23) related. Only a small percentage (3/51) of DLPN neurons responded during vestibular ocular reflex in the dark (VORd). We tested rNRTP neurons as described above and found the majority of neurons (35/43) were modulated during smooth pursuit or during motion of a large-field stimulus only (4/43). A significant proportion of our rNRTP gaze velocity neurons (10/18) were also modulated during VORd. We found that the majority of smooth pursuit related neurons in rNRTP were best classified as gaze velocity (18/35) or gaze acceleration (11/35) sensitive. The remaining neurons were classified as eye position or eye/head related. We used multiple linear-regression modeling to determine the relative contributions of eye, head and visual inputs to the responses of DLPN and rNRTP neurons. Our results support the suggestion that both DLPN and rNRTP play significant roles not only in control of smooth pursuit but also in control of gaze.
Cone Inputs in Macaque Primary Visual Cortex
Authors: Johnson Elizabeth N. , Hawken Michael J. , Shapley Robert
Published: May 2004

To understand the role of primary visual cortex (V1) in color vision, we measured directly the input from the 3 cone types in macaque V1 neurons. Cells were classified as luminance-preferring, color-luminance, or color-preferring from the ratio of the peak amplitudes of spatial frequency responses to red/green equiluminant and to black/white (luminance) grating patterns, respectively. In this study we used L-, M-, and S-cone–isolating gratings to measure spatial frequency response functions for each cone type separately. From peak responses to cone-isolating stimuli we estimated relative cone weights and whether cone inputs were the same or opposite sign. For most V1 cells the relative S-cone weight was <0.1. All color-preferring cells were cone opponent and their L/M cone weight ratio was clustered around a value of –1, which is roughly equal and opposite L and M cone signals. Almost all cells (88%) classified as luminance cells were cone nonopponent, with a broad distribution of cone weights. Most cells (73%) classified as color-luminance cells were cone opponent. This result supports our conclusion that V1 color-luminance cells are double-opponent. Such neurons are more sensitive to color boundaries than to areas of color and thereby could play an important role in color perception. The color-luminance population had a broad distribution of L/M cone weight ratios, implying a broad distribution of preferred colors for the double-opponent cells.
Effect of a Central Fixation Light on Auditory Spatial Responses in Area LIP
Authors: Gifford Gordon W. , Cohen Yale E.
Published: May 2004

A recent report demonstrated that, while fixating a central light, lateral intraparietal area (LIP) neurons are not modulated by the location of auditory stimuli until monkeys learn to saccade to the location of an auditory stimulus. This finding suggests that auditory spatial responses in area LIP are dependent on auditory-saccadic training. We found that, in monkeys that had not been trained to make behavioral responses to auditory stimuli, LIP neurons are modulated by auditory-stimulus location when a central light is not present in the environment. These results indicate that LIP auditory responses are not wholly dependent on behavioral training with auditory stimuli.
Intracortical Pathways Determine Breadth of Subthreshold Frequency Receptive Fields in Primary Auditory Cortex
Authors: Kaur Simranjit , Lazar Ronit , Metherate Raju
Published: May 2004

To examine the basis of frequency receptive fields in auditory cortex (ACx), we have recorded intracellular (whole cell) and extracellular (local field potential, LFP) responses to tones in anesthetized rats. Frequency receptive fields derived from excitatory postsynaptic potentials (EPSPs) and LFPs from the same location resembled each other in terms of characteristic frequency (CF) and breadth of tuning, suggesting that LFPs reflect local synaptic (including subthreshold) activity. Subthreshold EPSP and LFP receptive fields were remarkably broad, often spanning five octaves (the maximum tested) at moderate intensities (40–50 dB above threshold). To identify receptive-field features that are generated intracortically, we microinjected the GABAA receptor agonist muscimol (0.2–5.1 mM, 1–5 μl) into ACx. Muscimol dramatically reduced LFP amplitude and reduced receptive-field bandwidth, implicating intracortical contributions to these features but had lesser effects on CF response threshold or onset latency, suggesting minimal loss of thalamocortical input. Reversal of muscimol's inhibition preferentially at the recording site by diffusion from the recording pipette of the GABAA receptor antagonist picrotoxin (0.01–100 μM) disinhibited responses to CF stimuli more than responses to spectrally distant, non-CF stimuli. We propose that thalamocortical and intracortical pathways preferentially contribute to responses evoked by CF and non-CF stimuli, respectively, and that intracortical projections linking frequency representations determine the breadth of receptive fields in primary ACx. Broad, subthreshold receptive fields may distinguish ACx from subcortical auditory relay nuclei, promote integrated responses to spectrotemporally complex stimuli, and provide a substrate for plasticity of cortical receptive fields and maps.
Pursuit-Related Neurons in the Supplementary Eye Fields: Discharge During Pursuit and Passive Whole Body Rotation
Authors: Fukushima Junko , Akao Teppei , Takeichi Norihito , Kurkin Sergei , Kaneko Chris R. S. , Fukushima Kikuro
Published: May 2004

The primate frontal cortex contains two areas related to smooth-pursuit: the frontal eye fields (FEFs) and supplementary eye fields (SEFs). To distinguish the specific role of the SEFs in pursuit, we examined discharge of a total of 89 pursuit-related neurons that showed consistent modulation when head-stabilized Japanese monkeys pursued a spot moving sinusoidally in fronto-parallel planes and/or in depth and with or without passive whole body rotation. During smooth-pursuit at different frequencies, 43% of the neurons tested (17/40) exhibited discharge amplitude of modulation linearly correlated with eye velocity. During cancellation of the vestibulo-ocular reflex and/or chair rotation in complete darkness, the majority of neurons tested (91% = 30/33) responded. However, only 17% of the responding neurons (4/30) were modulated in proportion to gaze (eye-in-space) velocity during pursuit-vestibular interactions. When the monkeys fixated a stationary spot, 20% of neurons tested (7/34) responded to motion of a second spot. Among the neurons tested for both smooth-pursuit and vergence tracking ( n = 56), 27% (15/56) discharged during both, 62% (35/56) responded during smooth-pursuit only, and 11% (6/56) during vergence tracking only. Phase shifts (relative to stimulus velocity) of responding neurons during pursuit in frontal and depth planes and during chair rotation remained virtually constant (≤1 Hz). These results, together with the robust vestibular-related discharge of most SEF neurons, show that the discharge of the majority of SEF pursuit-related neurons is quite distinct from that of caudal FEF neurons in identical task conditions, suggesting that the two areas are involved in different aspects of pursuit-vestibular interactions including predictive pursuit.
Large Releasable Pool of Synaptic Vesicles in Chick Cochlear Hair Cells
Authors: Eisen Marc D. , Spassova Maria , Parsons Thomas D.
Published: May 2004

Hearing requires the hair cell synapse to maintain notable temporal fidelity (≤1 ms) while sustaining neurotransmitter release for prolonged periods of time (minutes). Here we probed the properties and possible anatomical substrate of prolonged neurotransmitter release by using electrical measures of cell surface area as a proxy for neurotransmitter release to study hair cell exocytosis evoked by repetitive stimuli. We observed marked depression of exocytosis by chick tall hair cells. This exocytic depression cannot be explained by calcium current inactivation, presynaptic autoinhibition by metabotropic glutamate receptors, or postsynaptic receptor desensitization. Rather, cochlear hair cell exocytic depression resulted from the exhaustion of a functional vesicle pool. This releasable vesicle pool is large, totaling approximately 8,000 vesicles, and is nearly 10 times greater than the number of vesicles tethered to synaptic ribbons. Such a large functional pool suggests the recruitment of cytoplasmic vesicles to sustain exocytosis, important for maintaining prolonged, high rates of neural activity needed to encode sound.
Interactions Between Light-Induced Currents, Voltage-Gated Currents, and Input Signal Properties inDrosophilaPhotoreceptors
Authors: Niven Jeremy E. , Vähäsöyrinki Mikko , Juusola Mikko , French Andrew S.
Published: May 2004

Voltage-gated K+channels are important in neuronal signaling, but little is known of their interactions with receptor currents or their behavior during natural stimulation. We used nonparametric and parametric nonlinear modeling of experimental responses, combined with Hodgkin–Huxley style simulation, to examine the roles of K+channels in forming the responses of wild-type (WT) and Shaker mutant ( Sh14) Drosophila photoreceptors to naturalistic stimulus sequences. Naturalistic stimuli gave results different from those of similar experiments with white noise stimuli. Sh14responses were larger and faster than WT. Simulation indicated that, in addition to eliminating the Shaker current, the mutation changed the current flowing through light-dependent channels [light-induced current (LIC)] and increased the delayed rectifier current. Part of the change in LIC could be attributed to direct feedback from the voltage-sensitive ion channels to the light-sensitive channels by the membrane potential. However, we argue that other changes occur in the light detecting machinery of Sh14mutants, possibly during photoreceptor development.
Distribution of Motor Unit Force in Human Extensor Digitorum Assessed By Spike-Triggered Averaging and Intraneural Microstimulation
Authors: Keen Douglas A. , Fuglevand Andrew J.
Published: May 2004

A peculiar aspect of the muscular organization of the human hand is that the main flexors and extensors of the fingers are muscles that each give rise to four parallel tendons that insert on all the fingers. It has been hypothesized that these multi-tendoned muscles are comprised of functional compartments, with each finger controlled by a discrete population of motor units. The purpose of this study was to determine the force distribution across the four fingers for motor units in human extensor digitorum (ED), a multi-tendoned muscle that extends the fingers. The force distribution was assessed by spike-triggered averaging and intraneural microstimulation for 233 and 18 ED units, respectively. A selectivity index from 0 (force equally distributed across the fingers) to 1.0 (force concentrated on a single finger) was used to quantify the distribution of motor unit force across the four digits. The mean selectivity index was high for ED motor units assessed with intraneural microstimulation (0.90 ± 0.28) and was significantly greater than that obtained with spike-triggered averaging (0.38 ± 0.14). Therefore it is likely that each finger is acted on by ED through a discrete population of motor units and that weak synchrony between motor units in different compartments of ED may have contributed to the appearance of spike-triggered average force on multiple fingers. Moreover, the high selectivity of motor units for individual fingers may provide the mechanical substrate needed for highly fractionated movements of the human hand.
Neuronal Encoding of Ultrasonic Sound by a Fish
Authors: Plachta Dennis T. T. , Song Jiakun , Halvorsen Michele B. , Popper Arthur N.
Published: May 2004

Many species of odontocete cetaceans (toothed whales) use high-frequency clicks (60–170 kHz) to identify objects in their environment, including potential prey. Behavioral studies have shown that American shad, Alosa sapidissima, can detect ultrasonic signals similar to those of odontocetes that are potentially their predators. American shad also show strong escape behavior in response to ultrasonic pulses between 70 and 110 kHz and can determine the location of the sound source at least in the horizontal plane. The present study examines physiological aspects of ultrasound detection by American shad and provides the first insights into the neural encoding of ultrasound signals in any nonmammalian vertebrate. The recordings were obtained by penetration through the cerebellar surface. All but two units responded exclusively to ultrasound. Ultrasound-sensitive units did not phase-couple to any stimulus frequency. Some units resembled the response of constant latency neurons found in the ventral nucleus of the lateral lemniscus of bats. We suggest that ultrasonic and sonic signals are processed along different pathways in Alosa. The ultrasonic pathway in Alosa appears to be a feature detector that is likely to be adapted (e.g., frequency, intensity) to odontocete echolocation signals.
A Method to Estimate Synaptic Conductances From Membrane Potential Fluctuations
Authors: Rudolph Michael , Piwkowska Zuzanna , Badoual Mathilde , Bal Thierry , Destexhe Alain
Published: May 2004

In neocortical neurons, network activity can activate a large number of synaptic inputs, resulting in highly irregular subthreshold membrane potential ( Vm) fluctuations, commonly called “synaptic noise.” This activity contains information about the underlying network dynamics, but it is not easy to extract network properties from such complex and irregular activity. Here, we propose a method to estimate properties of network activity from intracellular recordings and test this method using theoretical and experimental approaches. The method is based on the analytic expression of the subthreshold Vm distribution at steady state in conductance-based models. Fitting this analytic expression to Vm distributions obtained from intracellular recordings provides estimates of the mean and variance of excitatory and inhibitory conductances. We test the accuracy of these estimates against computational models of increasing complexity. We also test the method using dynamic-clamp recordings of neocortical neurons in vitro. By using an on-line analysis procedure, we show that the measured conductances from spontaneous network activity can be used to re-create artificial states equivalent to real network activity. This approach should be applicable to intracellular recordings during different network states in vivo, providing a characterization of the global properties of synaptic conductances and possible insight into the underlying network mechanisms.
Primary Afferent Stimulation Differentially Potentiates Excitatory and Inhibitory Inputs to Spinal Lamina II Outer and Inner Neurons
Authors: Pan Yu-Zhen , Pan Hui-Lin
Published: May 2004

Spinal lamina II (substantia gelatinosa) neurons play an important role in processing of nociceptive information from primary afferent nerves. Anatomical studies suggest that neurons in the outer (lamina IIo) and inner (lamina IIi) zone of lamina II receive distinct afferent inputs. The functional significance of this preferential afferent termination in lamina II remains unclear. In this study, we examined the differential synaptic inputs to neurons in lamina IIo and IIi in response to primary afferent stimulation. Whole cell voltage-clamp recordings were performed on neurons in lamina IIo and IIi of the rat spinal cord slice under visual guidance. Capsaicin (1 μM) significantly increased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in all 27 lamina IIo neurons and significantly increased the amplitude of mEPSCs in 12 of 27 lamina IIo neurons. However, capsaicin only significantly increased the frequency of mEPSCs in 9 of 22 (40.9%) lamina IIi neurons and increased the amplitude of mEPSCs in 6 of these 9 neurons. Furthermore, the peak amplitude of EPSCs, evoked by electrical stimulation of the attached dorsal root, in 40 lamina IIo neurons was significantly greater than that [160.5 ± 16.7 vs. 87.0 ± 10.4 (SE) pA] in 37 lamina IIi neurons. On the other hand, the peak amplitude of evoked inhibitory postsynaptic currents (IPSCs) in 40 lamina IIo neurons was significantly smaller than that (103.1 ± 11.6 vs. 258.4 ± 24.4 pA) in 37 lamina IIi neurons. In addition, the peak amplitudes of both EPSCs and IPSCs, evoked by direct stimulation of lamina II, were similar in lamina IIo and IIi neurons. This study provides new information that stimulation of primary afferents differentially potentiates synaptic inputs to neurons in lamina IIo and IIi. The quantitative difference in excitatory and inhibitory synaptic inputs to lamina IIo and IIi neurons may be important for integration of sensory information from primary afferent nerves.
Presumed Inhibitory Neurons in the Macaque Inferior Temporal Cortex: Visual Response Properties and Functional Interactions With Adjacent Neurons
Authors: Tamura Hiroshi , Kaneko Hidekazu , Kawasaki Keisuke , Fujita Ichiro
Published: May 2004

Neurons in area TE of the monkey inferior temporal cortex respond selectively to images of particular objects or their characteristic visual features. The mechanism of generation of the stimulus selectivity, however, is largely unknown. This study addresses the role of inhibitory TE neurons in this process by examining their visual response properties and interactions with adjacent target neurons. We applied cross-correlation analysis to spike trains simultaneously recorded from pairs of adjacent neurons in anesthetized macaques. Neurons whose activity preceded a decrease in activity from their partner were presumed to be inhibitory neurons. Excitatory neurons were also identified as the source neuron of excitatory linkage as evidenced by a sharp peak displaced from the 0-ms bin in cross-correlograms. Most inhibitory neurons responded to a variety of visual stimuli in our stimulus set, which consisted of several dozen geometrical figures and photographs of objects, with a clear stimulus preference. On average, 10% of the stimuli increased firing rates of the inhibitory neurons. Both excitatory and inhibitory neurons exhibited a similar degree of stimulus selectivity. Although inhibitory neurons occasionally shared the most preferred stimuli with their target neurons, overall stimulus preferences were less similar between adjacent neurons with inhibitory linkages than adjacent neurons with common inputs and/or excitatory linkages. These results suggest that inhibitory neurons in area TE are activated selectively and exert stimulus-specific inhibition on adjacent neurons, contributing to shaping of stimulus selectivity of TE neurons.
Epidemiology of Nephrolithiasis Today
Authors: Amato M. , Lusini M.L. , Nelli F.
Published: May 2004

The epidemiology of nephrolithiasis differs according to geographical area and socio-economic conditions. In Italy the prevalence of the disease in 1993 was 17.2/1,000 inhabitants, most patients are men and elderly. The relative risk increased in subjects with family history for calculosis, with the tendency to eat protein-rich food and with overweight and body mass index (MBI) >32 kg/m2. Calcium oxalate and/or phosphate stones account for almost 70% of all renal stones observed in economically developed countries.