bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug‐resistant genes and serotypes of pneumococcal strains of community‐acquired pneumonia among adults in Japan
Authors: OISHI Kazunori , YOSHIMINE Hiroyuki , WATANABE Hiroshi , WATANABE Kiwao , TANIMURA Susumu , KAWAKAMI Kenji , IWAGAKI Akitaka , NAGAI Hideaki , GOTO Hajime , KUDOH Shoji , KURIYAMA Takayuki , FUKUCHI Yoshinosuke , MATSUSHIMA Toshiharu , SHIMADA Kaoru , MATSUMOTO Keizo , NAGATAKE Tsuyoshi
Published: May 2006

Background:  A high frequency of drug‐resistant pneumococci has been reported in Asian countries. Few data on the drug‐resistance or serotype of pneumococcal strains responsible for community‐acquired pneumonia (CAP), however, are available for the past two decades in Japan.

Methodology:  Susceptibility to antibiotics and the genotype of antibiotic‐resistant genes and serotypes of Streptococcus pneumoniae isolates from 114 adult patients with CAP were examined in a nationwide study in Japan between 2001 and 2003.

Results:  Most of the cases were non‐bacteraemic pneumonia and the case fatality rate was 4.4%. The most frequent genotype of the pbp gene was pbp1a + 2x + 2b (gPRSP; 36.8%) followed by pbp 2x (28.1%) and of the macrolide‐resistant gene, it was ermB (50.0%). The most common serotype was 19F (29.1%), followed by serotype 23F (13.2%), 6B (12.3%) and 3 (11.4%). The coverage of serotypes of isolates by a 23‐valent pneumococcal polysaccharide vaccine (PPV) would be 82.5% in these patients with CAP. Most of strains with serotypes 19F and 23F were gPRSP. A cluster of serotype 3 strains associated with the pbp 2x and ermB gene was also noted.

Conclusion:  A high frequency of altered pbp gene mutations or of macrolide‐related genes and a high serotype coverage by the 23‐valent PPV found in our study of pneumococcal pneumonia facilitates attempts to increase the coverage rate of the 23‐valent PPV in adults older than 65 years in Japan.
Effect of corticosteroids on adult varicella pneumonia: Cohort study and literature review
Authors: ADHAMI Naeem , ARABI Yaseen , RAEES Ahmed , AL‐SHIMEMERI Abdullah , UR‐RAHMAN Masood , MEMISH Ziad A.
Published: May 2006

Background:  Varicella pneumonia (VP) is a serious entity associated with morbidity and mortality. There have been sporadic reports using corticosteroids in life‐threatening VP. We report a case series of VP to examine the outcome and the effect of corticosteroid use.

Methods:  A retrospective chart review was conducted on all adult patients admitted to a tertiary care hospital with VP during a 14‐year period. We documented oxygenation (SpO2, PaO2/FIO2) on admission and after 48 h, whether the patients were admitted to an intensive care unit (ICU), the use of mechanical ventilation, ICU and hospital length of stay (LOS) and patient outcome. We compared those patients who received corticosteroids with those who did not.

Results:  We identified 19 patients with VP. Ten received corticosteroids, in addition to antiviral and supportive treatment. Patients who received corticosteroids were significantly more hypoxaemic on admission and all were admitted to ICU with seven of them intubated. Only two of the nine in non‐steroid group were intubated. Despite their greater severity, the corticosteroid group showed a much more rapid improvement in oxygenation and a trend towards shorter duration of mechanical ventilation. The duration of ICU and hospital LOS were not significantly different. All patients survived.

Conclusions:  Corticosteroids in severe VP accelerate the physiological recovery and may shorten the duration of mechanical ventilation.
The existence of opioid receptors in the cochlea of guinea pigs
Authors: Jongkamonwiwat Nopporn , Phansuwan‐Pujito Pansiri , Casalotti Stefano O. , Forge Andrew , Dodson Hilary , Govitrapong Piyarat
Published: May 2006

Several independent investigations have demonstrated the presence of opioid peptides in the inner ear organ of Corti and in particular in the efferent nerve fibers innervating the cochlear hair cells. However, the precise innervation pattern of opioid fibers remains to be investigated. In the present study the expression of opioid receptors and their peptides is demonstrated in young adult guinea pig cochlea. Opioid receptors are mainly expressed in hair cells of the organ of Corti and in inner and outer spiral bundles with different characteristics for each type of receptor. Co‐localization studies were employed to compare the distribution of mu‐, delta‐ and kappa‐opioid receptors and their respective peptides, β‐endorphin, leu‐enkephalin and dynorphin. Additionally, immunostaining of synaptophysin was used in this study to identify the presynaptic site. Immunoreactivity for enkephalin and dynorphin was found in the organ of Corti. Leu‐enkephalin was co‐localized with synaptophysin prominently in the inner spiral bundle (ISB). Dynorphin was co‐localized with synaptophysin in both inner and outer spiral bundles. Delta‐opioid receptor was most prominently co‐localized with its peptide in the ISB bundle. Kappa‐opioid receptor was seemingly present with dynorphin in both inner and outer spiral bundles. The co‐staining of both peptides and receptors with synaptophysin in the same areas suggests that some of the opioid receptors may act as auto‐receptors. The results provide further evidence that opioids may function as neurotransmitters or neuromodulators in the cochlea establishing the basis for further electrophysiological and pharmacological investigations to understand better the roles of the opioid system in auditory function.
Personality Architecture and the FFM in Organisational Psychology
Authors: Wood Robert E. , Beckmann Nadin
Published: May 2006

Cervone, Shadel, Smith, and Fiori (2006) outline an approach to the study of self‐regulation that is consistent with but extends research on self‐regulation and motivation within organisational psychology. At the same time, their model represents a new perspective for the study of personality processes within organisations and one that conflicts with the existing personality research programmes focused on the five factor model (FFM). We outline the points of differentiation between the two approaches and suggest strategies that we believe will allow personality researchers to build the personality architectures for the trait behaviours derived from the FFM. We also categorise the mediating mechanisms studied in organisational psychology in the KAPA model of Cervone et al. and highlight the need for related frameworks covering affective units and personal competencies in personality architecture.
Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a meta‐analysis of randomized double‐blind controlled trials
Authors: Song Y. , He K. , Levitan E. B. , Manson J. E. , Liu S.
Published: May 2006

Aims  The aim of this study was to assess the evidence on the effect of oral magnesium supplementation on glycaemic control in patients with Type 2 diabetes.

Methods  We searched the electronic databases of medline, embase and the Cochrane Controlled Trials Register up to January 2005. We identified nine randomized double‐blind controlled trials with a total of 370 patients with Type 2 diabetes and of duration 4–16 weeks. The median dose of oral magnesium supplementation was 15 mmol/day (360 mg/day) in the treatment groups. The primary outcome was glycaemic control, as measured by glycated haemoglobin (HbA1c) or fasting blood glucose levels; the secondary outcomes included body mass index, blood pressure (BP) and lipids. Using a random‐effects model, we calculated the weighted mean differences (WMD) and 95% confidence interval (CI).

Results  After a median duration of 12 weeks, the weighted mean post‐intervention fasting glucose was significantly lower in the treatment groups compared with the placebo groups [−0.56 mmol/l (95% CI, −1.10 to −0.01); P for heterogeneity = 0.02]. The difference in post‐intervention HbA1c between magnesium supplementation groups and control groups was not significant [−0.31% (95% CI, −0.81 to 0.19); P for heterogeneity = 0.10]. Neither systolic nor diastolic BP was significantly changed. Magnesium supplementation increased on high‐density lipoprotein (HDL) cholesterol levels [0.08 mmol/l (95% CI, 0.03 to 0.14); P for heterogeneity = 0.36] but had no effect on total cholesterol, low‐density lipoprotein (LDL) cholesterol and triglyceride.

Conclusions  Oral magnesium supplementation for 4–16 weeks may be effective in reducing plasma fasting glucose levels and raising HDL cholesterol in patients with Type 2 diabetes, although the long‐term benefits and safety of magnesium treatment on glycaemic control remain to be determined.
Promoting indigenous entrepreneurship through small‐scale contract farming: The poultry sector in Sarawak, Malaysia
Authors: Morrison Philip S. , Murray Warwick E. , Ngidang Dimbab
Published: May 2006

Studies have consistently shown that in the relatively unregulated environments of the global economic periphery contract farming has led to highly regressive socioeconomic outcomes. Contract farming is not inherently regressive for the small farm sector however. In the state of Sarawak, Malaysia, contract farming is used as part of an affirmative action programme that trains indigenous smallholders in commercial poultry production. The public sector quasi‐market constructed by state purchasers and subsidiary suppliers is one that recognizes the smallholders’ limited access to collateral and technical skills and their need to supplement rather than totally replace the incomes already derived from diverse agricultural and off‐farm sources. The state‐administered contract scheme is part of a broader national goal to eradicate poverty, raise rural incomes and ultimately, develop indigenous entrepreneurship. In the shorter and medium term, as the paper shows, the small‐scale public contract scheme, which itself operates within the protected domestic poultry sector in Sarawak, is more likely to support disadvantaged ‘bumiputra minorities’ than produce a pool of competitive entrepreneurs.
GIS‐based flood hazard mapping at different administrative scales: A case study in Gangetic West Bengal, India
Authors: Sanyal Joy , Lu X.X.
Published: May 2006

This paper addresses the need for an efficient and cost‐effective methodology for preparing flood hazard maps in data poor countries, particularly those under a monsoon regime where floods pose a recurrent danger. Taking Gangetic West Bengal, India, as an example and using available historical data from government agencies, the study compiled a regional map indicating hazard prone subregional areas for further detailed investigation, thereby isolating actual high risk localities. Using a GIS (Geographical Information System), a composite hazard index was devised incorporating variables of flood frequency, population density, transportation networks, access to potable water, and availability of high ground and maximum risk zones were mapped accordingly. A digital elevation model derived from high resolution imagery available in the public domain was used to calculate elevated areas suitable for temporary shelter during a flood. Selecting administrative units of analysis at the lowest possible scales – rural development blocks (regional) and revenue villages (subregional) – also ensures that hazard mapping is prepared in line with the existing rural planning and administrative authorities responsible for remedial intervention.
Groundwater discharges in the Baltic Sea: survey and quantification using a schlieren technique application
Authors: KARPEN V. , THOMSEN L. , SUESS ERWIN
Published: May 2006

Groundwater seeps are known to occur in Eckernförde Bay, Baltic Sea. Their discharge rate and dispersion were investigated with a new schlieren technique application, which is able to visualize heterogeneous water parcels with density anomalies down to Δσt = 0.049 on the scale of millimeters. With the use of an inverted funnel, discharged fluids can be captured and the outflow velocity can be determined. Overall, 46 stations could be categorized by three different cases: active vent sites, seep‐influenced sites, and non‐seep sites. New seep locations were discovered, even at shallow near‐shore sites, lacking prominent sediment depression, which indicate submarine springs. The detection of numerous seeps was possible and the groundwater‐influenced area was defined to be approximately 6.3 km2. Flow rates of between 0.05 and 0.71 l m−2 min−1 were measured. A single focused fluid plume, which was not disturbed by the funnel was recorded and revealed a flux of 59.6 ± 20 ml cm−2 min−1 and it was calculated that this single focused plume would be strong enough to produce a flow rate through the funnel of 1.32 ± 0.44 l m−2 min−1. The effect of different seep‐meter funnel sizes is discussed.
Mitochondrial DNA Portrait of Latvians: Towards the Understanding of the Genetic Structure of Baltic‐Speaking Populations
Authors: Pliss L. , Tambets K. , Loogväli E.‐L. , Pronina N. , Lazdins M. , Krumina A. , Baumanis V. , Villems R.
Published: May 2006

Mitochondrial DNA (mtDNA) variation was investigated in a sample of 299 Latvians, a Baltic‐speaking population from Eastern Europe. Sequencing of the first hypervariable segment (HVS‐I) in combination with analysis of informative coding region markers revealed that the vast majority of observed mtDNAs belong to haplogroups (hgs) common to most European populations. Analysis of the spatial distribution of mtDNA haplotypes found in Latvians, as well as in Baltic‐speaking populations in general, revealed that they share haplotypes with all neighbouring populations irrespective of their linguistic affiliation. Hence, the results of our mtDNA analysis show that the previously described sharp difference between the Y‐chromosomal hg N3 distribution in the paternally inherited gene pool of Baltic‐speaking populations and of other European Indo‐European speakers does not have a corresponding maternal counterpart.
Facts and Values in Risk Analysis for Environmental Toxicants
Authors: Whittemore Alice S.
Published: May 2006

The U.S. Office of Science and Technology Policy describes toxic substance regulation as composed of two stages. Stage I (facts) uses empirical data and scientific judgment to characterize human exposure and risk. Stage II (values) uses social and political judgment to decide regulatory action based on significance of the risk, benefits of the agent, and costs of its control. This paper argues that such a view represents an unrealistic and unattainable goal. We present examples showing how values enter virtually every part of risk analysis, and we review work on the vagaries in human judgment concerning both facts and values. These issues indicate that U.S. regulatory policy needs reconsideration.
Islet hypertrophy following pancreatic disruption of Smad4 signaling
Authors: Simeone Diane M. , Zhang Lizhi , Treutelaar Mary K. , Zhang Lanjing , Graziano Kathleen , Logsdon Craig D. , Burant Charles F.
Published: May 2006

To investigate the role of transforming growth factor (TGF)-β family signaling in the adult pancreas, a transgenic mouse (E-dnSmad4) was created that expresses a dominant-negative Smad4 protein driven by a fragment of the elastase promoter. Although E-dnSmad4 mice have normal growth, pancreas weight, and pancreatic exocrine and ductal histology, beginning at 4–6 wk of age, E-dnSmad4 mice show an age-dependent increase in the size of islets. In parallel, an expanded population of replicating cells expressing the E-dnSmad4 transgene is found in the stroma between the enlarged islets and pancreatic ducts. Despite the marked enlargement, E-dnSmad4 islets contain normal ratios and spatial organization of endocrine cell subtypes and have normal glucose homeostasis. Replication of cells derived from primary duct cultures of wild-type mice, but not E-dnSmad4 mice, was inhibited by the addition of TGF-β family proteins, demonstrating a cell-autonomous effect of the transgene. These data show that, in the adult pancreas, TGF-β family signaling plays a role in islet size by regulating the growth of a pluripotent progenitor cell residing in the periductal stroma of the pancreas.
Modulation of Noxious and Non-Noxious Spinal Mechanical Transmission From the Rostral Medial Medulla in the Rat
Authors: Zhuo M. , Gebhart G. F.
Published: May 2006

Modulatory influences on spinal mechanical transmission from the rostral medial medulla (RMM) were studied. Noxious stimulation, produced by von Frey-like monofilaments, and non-noxious stimulation, produced by a soft brush, was applied to the glabrous skin of the hind foot. At 28 sties in RMM, electrical stimulation facilitated responses to noxious mechanical stimulation at low intensities (5–25 μA) and inhibited responses of the same neurons at greater intensities (50–100 μA) of stimulation. At 24 and 9 other sites in RMM, stimulation at all intensities only inhibited or only facilitated, respectively, responses to noxious mechanical stimulation of the hind foot. Stimulus-response functions to mechanical stimulation were shifted leftward by low intensities and decreased by high intensities of stimulation. Inhibitory influences were found to descend in the dorsolateral funiculi; facilitatory effects were contained in the ventral spinal cord. Descending modulation of non-noxious brush stimulation revealed biphasic facilitatory-inhibitory effects (9 sites in RMM), only inhibitory effects (14 sites) and only facilitatory effects (8 sites). The effects of electrical stimulation were replicated by intra-RMM administration of glutamate; a low concentration (0.25 nmol) facilitated and a greater concentration (2.5 nmol) inhibited spinal mechanical transmission, providing evidence that cells in RMM are sufficient to engage descending influences. Descending modulatory effects were specific for the site of stimulation, not for the spinal neuron, because modulation of the same neuron was different from different sites in RMM. These results show that spinal mechanical transmission, both noxious and non-noxious, is subject to descending influences, including facilitatory influences that may contribute to exaggerated responses to peripheral stimuli in some chronic pain states.
Analysis of Perisaccadic Field Potentials in the Occipitotemporal Pathway During Active Vision
Authors: Purpura Keith P. , Kalik Steven F. , Schiff Nicholas D.
Published: May 2006

Eye movement potentials (EMPs) associated with saccades appear in both subcortical and cortical structures of the primate visual system. In this study, EMPs are recorded across sites in the occipitotemporal (OT) pathway of monkeys performing a pattern-recognition task. We characterize pair recordings of saccade-triggered local field potentials (LFPs) in early extrastriate and inferotemporal regions of the ventral visual pathway using time–frequency spectrograms. Parameters of the spectrograms, including the centroids of identified regions of interest in the time–frequency plane, are extracted and analyzed. Comparisons among the distributions of the extracted parameters reveal that the occipital lobe EMPs are largely postsaccadic events centered at 100 ms after saccade onset that are typically not influenced in timing by the direction of the saccade or the appearance of a stimulus transient appearing either before or after the saccade. The occipital lobe EMPs also demonstrate a significant shift in frequency content during their transient time course that is influenced, in a few cases, by saccade direction. Temporal lobe EMPs, on the other hand, may be centered in either the presaccadic or postsaccadic intervals; the time of their appearance is significantly influenced by the direction of the saccade. Temporal lobe EMPs demonstrate less frequency modulation than those recorded in the occipital lobe. The prevalence of EMPs in the OT pathway suggests that many cortical regions important for pattern recognition can be modulated by saccades. The timing and frequency characteristics of these signals suggest that the nature of this perisaccadic modulation varies across the cortex.
Impact of Expected Reward on Neuronal Activity in Prefrontal Cortex, Frontal and Supplementary Eye Fields and Premotor Cortex
Authors: Roesch Matthew R. , Olson Carl R.
Published: May 2006

In several regions of the macaque brain, neurons fire during delayed response tasks at a rate determined by the value of the reward expected at the end of the trial. The activity of these neurons might be related either to the internal representation of the appetitive value of the expected reward or to motivation-dependent variations in the monkey's level of motor preparation or motor output. According to the first interpretation, reward-related activity should be most prominent in areas affiliated with the limbic system. According to the second interpretation, it should be most prominent in areas affiliated with the motor system. To distinguish between these alternatives, we carried out single-neuron recording while monkeys performed a memory-guided saccade task in which a visual cue presented early in each trial indicated whether the reward would be large or small. Neuronal activity accompanying task performance was monitored in the dorsolateral prefrontal cortex (PFC), the frontal eye field (FEF), a transitional zone caudal to the frontal eye field (FEF/PM), premotor cortex (PM), the supplementary eye field (SEF), and the rostral part of the supplementary motor area (SMAr). The tendency for neuronal activity to increase after cues that predicted a large reward became progressively stronger in progressively more posterior areas both in the lateral sector of the frontal lobe (PFC < FEF < FEF/PM < PM) and in the medial sector (SEF < SMAr). The very strong reward-related activity of premotor neurons was presumably attributable to the monkey's motivation-dependent level of motor preparation or motor output. This finding points to the need to determine whether reward-related activity in other nonlimbic brain areas, including dorsolateral prefrontal cortex and the dorsal striatum, genuinely represents the value of the expected reward or, alternatively, is related to motivational modulation of motor signals.
Visceromotor and Spinal Neuronal Responses to Colorectal Distension in Rats With Aldosterone Onto the Amygdala
Authors: Qin Chao , Meerveld Beverley Greenwood-Van , Foreman Robert D.
Published: May 2006

Stereotaxic delivery of corticosterone onto the amygdala produces colorectal hypersensitivity through activation of lumbosacral spinal neurons. Since corticosterone activates both the mineralocorticoid (MR) and glucocorticoid (GR) receptors, the aim of this study was to determine the importance of MRs in the regulation of colorectal hypersensitivity through the use of aldosterone that preferentially binds to MRs. Fischer-344 rats received either aldosterone ( n = 18)- or cholesterol (control, n = 18)-containing micropellets bilaterally placed stereotaxically on the dorsal margin of the amygdala. After 1 wk, colorectal sensitivity to distension (30 mmHg) was measured in a subgroup of rats ( n = 8/group). In other rats ( n = 10/group), extracellular potentials of single L6–S1 spinal neurons in response to colorectal distension (CRD; 10–80 mmHg) were recorded. In aldosterone-implanted rats, CRD produced a greater visceromotor behavioral response compared with cholesterol controls (19 ± 0.5 vs. 11.5 ± 2.7; P < 0.01). A total of 68/182 (37%) and 56/167 (34%) of spinal neurons responded to noxious CRD in aldosterone-implanted and control groups, respectively. A total of 36/42 (86%) neurons excited by CRD had spontaneous activity in aldosterone-implanted groups compared with control (19/33, 58%, P < 0.01). Neurons with low thresholds for excitatory responses to CRD were seen more frequently in aldosterone-implanted rats than those in the control group (35/39 vs. 18/31, P < 0.05). Maximal excitatory responses of neurons to CRD in aldosterone-implanted rats were significantly greater (23.9 ± 2.2 vs. 16.4 ± 2.0 imp/s, P < 0.05), and the durations were longer (34.3 ± 2.7 vs. 24.9 ± 1.4 s, P < 0.05) than those in control group. Finally, a greater number of neurons had wide dynamic range responses to somatic stimulation in aldosterone-treated rats compared with cholesterol controls. Our findings suggest that, in the amygdala, MR receptor–mediated mechanisms are likely involved in descending pathways onto lumbosacral spinal neurons that induce colorectal hypersensitivity to luminal distension.
Movement-Related Neuronal Activity Reflecting the Transformation of Coordinates in the Ventral Premotor Cortex of Monkeys
Authors: Kurata Kiyoshi , Hoshi Eiji
Published: May 2006

We examined how the transformation of coordinates from visual to motor space is reflected by neuronal activity in the ventral premotor cortex (PMv) of monkeys. Three monkeys were trained to reach with their right hand for a target that appeared on a screen. While performing the task, the monkeys wore prisms that shifted the image of the target 10°, left or right, or wore no prisms, for a block of 200 trials. The nine targets were located in the same positions in visual space regardless of whether the prisms were present. Wearing the prisms required the monkeys to initiate a movement in a direction that was different from the apparent target location. Thus using the prisms, we could dissociate visual space from motor space. While the monkey performed the behavioral task, we recorded neuronal activity in the left PMv and primary motor cortex (MI), and various kinds of task-related neuronal activity were found in the motor areas. These included neurons that changed their activity during a reaction time (RT) period (the period between target presentation and movement onset), which were called “movement-related neurons” and selected for analysis. In these neurons, activity during a movement time (MT) period was also compared. Using general linear models for our statistical analysis, the neurons were then classified into four types: those whose activity was consistently dependent on location of targets in the visual coordinates regardless of whether the prisms were present or absent (V type); those that were consistently dependent on target location in the motor coordinates only; those that had different activity for both of the motor and visual coordinates; and those that had nondifferential activity for the two types of coordinates. The proportion of the four types of the neurons differed significantly between the PMv and MI. Most remarkably, neurons with V-type activity were almost exclusively recorded in the PMv and were almost exclusively found during the RT period. Such activity was never observed in an electromyogram of the working forelimb. Based on these observations, we postulate that the V and other types may represent the various intermediate stages of the transformation of coordinates and that the PMv plays a crucial role in transforming coordinates from visual to motor space.
Ionic Mechanisms Mediating Oscillatory Membrane Potentials in Wide-Field Retinal Amacrine Cells
Authors: Vigh Jozsef , Solessio Eduardo , Morgans Catherine W. , Lasater Eric M.
Published: May 2006

Particular types of amacrine cells of the vertebrate retina show oscillatory membrane potentials (OMPs) in response to light stimulation. Historically it has been thought the oscillations arose as a result of circuit properties. In a previous study we found that in some amacrine cells, the ability to oscillate was an intrinsic property of the cell. Here we characterized the ionic mechanisms responsible for the oscillations in wide-field amacrine cells (WFACs) in an effort to better understand the functional properties of the cell. The OMPs were found to be calcium (Ca2+) dependent; blocking voltage-gated Ca2+ channels eliminated the oscillations, whereas elevating extracellular Ca2+ enhanced them. Strong intracellular Ca2+ buffering (10 mM EGTA or bis-( o-aminophenoxy)- N,N,N′ ,N′-tetraacetic acid) eliminated any attenuation in the OMPs as well as a Ca2+-dependent inactivation of the voltage-gated Ca2+ channels. Pharmacological and immunohistochemical characterization revealed that WFACs express L- and N-type voltage-sensitive Ca2+ channels. Block of the L-type channels eliminated the OMPs, but ω-conotoxin GVIA did not, suggesting a different function for the N-type channels. The L-type channels in WFACs are functionally coupled to a set of calcium-dependent potassium ( K(Ca)) channels to mediate OMPs. The initiation of OMPs depended on penitrem-A-sensitive (BK) K(Ca) channels, whereas their duration is under apamin-sensitive (SK) K(Ca) channel control. The Ca2+ current is essential to evoke the OMPs and triggering the K(Ca) currents, which here act as resonant currents, enhances the resonance as an amplifying current, influences the filtering characteristics of the cell membrane, and attenuates the OMPs via CDI of the L-type Ca2+ channel.
Differential Expression of Three Distinct Potassium Currents in the Ventral Cochlear Nucleus
Authors: Rothman Jason S. , Manis Paul B.
Published: May 2006

In the ventral cochlear nucleus (VCN), neurons transform information from auditory nerve fibers into a set of parallel ascending pathways, each emphasizing different aspects of the acoustic environment. Previous studies have shown that VCN neurons differ in their intrinsic electrical properties, including the K+ currents they express. In this study, we examine these K+ currents in more detail using whole cell voltage-clamp techniques on isolated VCN cells from adult guinea pigs at 22°C. Our results show a differential expression of three distinct K+ currents. Whereas some VCN cells express only a high-threshold delayed-rectifier-like current ( IHT), others express IHT in combination with a fast inactivating current ( IA) and/or a slow-inactivating low-threshold current ( ILT). IHT, ILT, and IA, were partially blocked by 1 mM 4-aminopyridine. In contrast, only ILT was blocked by 10–100 nM dendrotoxin-I. A surprising finding was the wide range of levels of ILT, suggesting ILT is expressed as a continuum across cell types rather than modally in a particular cell type. IA, on the other hand, appears to be expressed only in cells that show little or no ILT, the Type I cells. Boltzmann analysis shows IHT activates with 164 ± 12 (SE) nS peak conductance, -14.3 ± 0.7 mV half-activation, and 7.0 ± 0.5 mV slope factor. Similar analysis shows ILT activates with 171 ± 22 nS peak conductance, -47.4 ± 1.0 mV half-activation, and 5.8 ± 0.3 mV slope factor.
Classification of Retinal Ganglion Cells: A Statistical Approach
Authors: Carcieri Stephen M. , Jacobs Adam L. , Nirenberg Sheila
Published: May 2006

Numerous studies have shown that retinal ganglion cells exhibit an array of responses to visual stimuli. This has led to the idea that these cells can be sorted into distinct physiological classes, such as linear versus nonlinear or on versus off. Although many classification schemes are widely accepted, few studies have provided statistical support to favor one scheme over another. Here we test whether some of the most widely used classification schemes can be statistically verified, using the mouse retina as the model system. We used a cluster analysis approach and focused on 4 standard response parameters: 1) response latency, 2) response duration, 3) relative amplitude of the on and off responses, and 4) degree of nonlinearity in the stimulus-to-response transformation. For each parameter, we plotted its distribution and tested quantitatively, using a bootstrap method, whether it divided into distinct clusters. Our analysis showed that mouse ganglion cells clustered into several groups based on response latency, duration, and relative amplitude of the on and off responses, but did not cluster into more than one group based on degree of nonlinearity—the latter formed a single, large, continuous group. Thus while some well-known schemes for classifying ganglion cells could be statistically verified, others could not. Knowledge of which schemes can be confirmed is important for building models of how retinal output is processed and how retinal circuits are built. Finally, this cluster analysis approach is general and can be used to test other classification proposals as well, both physiological and anatomical.
Neural Changes in Cat Auditory Cortex After a Transient Pure-Tone Trauma
Authors: Noreña Arnaud. J. , Tomita Masahiko , Eggermont Jos J.
Published: May 2006

Here we present the changes in cortical activity occurring within a few hours after a 1-h exposure to a 120-dB SPL pure tone (5 or 6 kHz). The changes in primary auditory cortex of 16 ketamine-anesthetized cats were assessed by recording, with two 8-microelectrode arrays, from the same multiunit clusters before and after the trauma. The exposure resulted in a peripheral threshold increase that stabilized after a few hours to on average 40 dB in the frequency range of 6–32 kHz, as measured by the auditory brain stem response. The trauma induced a shift in characteristic frequency toward lower frequencies, an emergence of new responses, a broadening of the tuning curve, and an increase in the maximum of driven discharges. In addition, the onset response after the trauma was of shorter duration than before the trauma. The results suggest the involvement of both a decrease and an increase in inhibition. They are discussed in terms of changes in central inhibition and its implications for tonotopic map plasticity.
Sodium Currents in Neurons From the Rostroventrolateral Medulla of the Rat
Authors: Rybak Ilya A. , Ptak Krzysztof , Shevtsova Natalia A. , McCrimmon Donald R.
Published: May 2006

Rapidly inactivating and persistent sodium currents have been characterized in acutely dissociated neurons from the area of rostroventrolateral medulla that included the pre-Bötzinger Complex. As demonstrated in many studies in vitro, this area can generate endogenous rhythmic bursting activity. Experiments were performed on neonate and young rats (P1-15). Neurons were investigated using the whole cell voltage-clamp technique. Standard activation and inactivation protocols were used to characterize the steady-state and kinetic properties of the rapidly inactivating sodium current. Slow depolarizing ramp protocols were used to characterize the noninactivating sodium current. The “window” component of the rapidly inactivating sodium current was calculated using mathematical modeling. The persistent sodium current was revealed by subtraction of the window current from the total noninactivating sodium current. Our results provide evidence of the presence of persistent sodium currents in neurons of the rat rostroventrolateral medulla and determine voltage-gated characteristics of activation and inactivation of rapidly inactivating and persistent sodium channels in these neurons.
Altered Control of Visual Fixation and Saccadic Eye Movements in Attention-Deficit Hyperactivity Disorder
Authors: Munoz Douglas P. , Armstrong Irene T. , Hampton Karen A. , Moore Kimberly D.
Published: May 2006

Attention-deficit hyperactivity disorder (ADHD) is characterized by the overt symptoms of impulsiveness, hyperactivity, and inattention. A frontostriatal pathophysiology has been hypothesized to produce these symptoms and lead to reduced ability to inhibit unnecessary or inappropriate behavioral responses. Oculomotor tasks can be designed to probe the ability of subjects to generate or inhibit reflexive and voluntary responses. Because regions of the frontal cortex and basal ganglia have been identified in the control of voluntary responses and saccadic suppression, we hypothesized that children and adults diagnosed with ADHD may have specific difficulties in oculomotor tasks requiring the suppression of reflexive or unwanted saccadic eye movements. To test this hypothesis, we measured eye movement performance in pro- and anti-saccade tasks of 114 ADHD and 180 control participants ranging in age from 6 to 59 yr. In the pro-saccade task, participants were instructed to look from a central fixation point toward an eccentric visual target. In the anti-saccade task, stimulus presentation was identical, but participants were instructed to suppress the saccade to the stimulus and instead look from the central fixation point to the side opposite the target. The state of fixation was manipulated by presenting the target either when the central fixation point was illuminated (overlap condition) or at some time after it disappeared (gap condition). In the pro-saccade task, ADHD participants had longer reaction times, greater intra-subject variance, and their saccades had reduced peak velocities and increased durations. In the anti-saccade task, ADHD participants had greater difficulty suppressing reflexive pro-saccades toward the eccentric target, increased reaction times for correct anti-saccades, and greater intra-subject variance. In a third task requiring prolonged fixation, ADHD participants generated more intrusive saccades during periods when they were required to maintain steady fixation. The results suggest that ADHD participants have reduced ability to suppress unwanted saccades and control their fixation behavior voluntarily, a finding that is consistent with a fronto-striatal pathophysiology. The findings are discussed in the context of recent neurophysiological data from nonhuman primates that have identified important control signals for saccade suppression that emanate from frontostriatal circuits.
Neuromedin U Depolarizes Rat Hypothalamic Paraventricular Nucleus Neurons In Vitro by Enhancing IH Channel Activity
Authors: Qiu De-Lai , Chu Chun-Ping , Shirasaka Tetsuro , Nabekura Takashi , Kunitake Takato , Kato Kazuo , Nakazato Masamitsu , Katoh Takahiko , Kannan Hiroshi
Published: May 2006

The effect of neuromedin U (NMU) on rat paraventricular nucleus (PVN) neurons was examined using whole cell patch-clamp recordings. Under current-clamp, 31% of PVN parvocellular neurons ( n = 243) were depolarized by 100 nM NMU, but magnocellular neurons were not affected. NMU (10 nM to 1 μM) resulted in increased basal firing rate and depolarization in a dose-dependent manner with an EC50 of 70 nM. NMU-induced depolarization was unaffected by co-perfusion with 0.5 μM TTX + 10 μM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) + 10 μM bicuculline. Extracellular application of 70 μM ZD 7288 completely inhibited NMU-induced depolarization. Under voltage-clamp, 1 μM NMU produced negligible inward current but did increase the hyperpolarization-activated current ( IH) at step potentials less than –80 mV. The effects of NMU on IH were voltage-dependent, and NMU shifted the IH conductance-voltage relationship ( V1/2) by about 10.8 mV and enhanced IH kinetics without changing the slope constant ( k). Extracellular application of 70 μM ZD 7288 or 3 mM Cs+ blocked IH and the effects of NMU in voltage-clamp. These results suggest that NMU selectively depolarizes the subpopulation of PVN parvocellular neurons via enhancement of the hyperpolarization-activated inward current.
Nitric Oxide Differentially Modulates ON and OFF Responses of Retinal Ganglion Cells
Authors: Wang Guo-Yong , Liets Lauren C. , Chalupa Leo M.
Published: May 2006

Several lines of evidence suggest that nitric oxide (NO) can regulate diverse retinal functions, but whether this gas is capable of modulating the visual responses of retinal output neurons has not been established. In the present study the effects of NO on rod-driven responses of retinal ganglion cells were tested by making whole cell patch-clamp recordings from morphologically identified ganglion cells in the isolated ferret retina. Bath application of l-arginine, the substrate of nitric oxide synthase, and S-nitroso- N-acetylpenicillamine, the NO donor, was found to differentially affect on and off discharge patterns. The introduction of these drugs significantly decreased visual responses of retinal ganglion cells, but the effects were more pronounced on off than on on discharges. The peak discharge rates of on responses were usually reduced by about 40%, but not completely blocked. In contrast, off responses were completely blocked in most cells. These differential effects were observed in on-off cells as well as in cells that yielded just on or off discharges. The off responses that were blocked by NO were also blocked by dl-2-amino-phosphonobutyric acid (APB) and strychnine, suggesting the involvement of the APB-sensitive rod pathway.
Septal Modulation of Excitatory Transmission in Hippocampus
Authors: Colgin Laura Lee , Kramár Enikö A. , Gall Christine M. , Lynch Gary
Published: May 2006

Application of the acetylcholinesterase inhibitor physostigmine to conventional hippocampal slices caused a significant reduction of field excitatory postsynaptic potentials (EPSPs) elicited by single pulse stimulation to the medial perforant path. Similar but smaller effects were obtained in the lateral perforant path and other excitatory pathways within hippocampus. The reductions were blocked by atropine, were not accompanied by evident changes in the EPSP waveform, and were eliminated by lesions to the cholinergic septo-hippocampal projections. Antidromic responses to mossy fiber stimulation, recorded in stratum granulosum, were not affected by the drug. However, paired-pulse facilitation was reliably increased, indicating that the depressed synaptic responses were secondary to reductions in transmitter release. The absence of cholinergic axo-axonic connections in the molecular layer suggests that physostigmine reduces presynaptic release by increasing retrograde signaling from the granule cells. In accord with this, an antagonist of the CB1 cannabinoid receptor eliminated the effects of physostigmine on synaptic responses, while an antagonist of the presynaptically located m2 muscarinic acetylcholine receptor did not. This is in contrast to previously reported effects involving application of cholinergic agonists, in which presynaptic inhibition likely results from direct activation of presynaptically located muscarinic receptors. In summary, it is proposed that the cholinergic inputs from the septum to the middle molecular layer modulate, via endocannabinoid release, the potency of the primary excitatory afferent of hippocampus.
Timing of Network Synchronization By Refractory Mechanisms
Authors: Wiedemann Urs Achim , Lüthi Anita
Published: May 2006

Even without active pacemaker mechanisms, temporally patterned synchronization of neural network activity can emerge spontaneously and is involved in neural development and information processing. Generation of spontaneous synchronization is thought to arise as an alternating sequence between a state of elevated excitation followed by a period of quiescence associated with neuronal and/or synaptic refractoriness. However, the cellular factors controlling recruitment and timing of synchronized events have remained difficult to specify, although the specific temporal pattern of spontaneous rhythmogenesis determines its impact on developmental processes. We studied spontaneous synchronization in a model of 600–1,000 integrate-and-fire neurons interconnected with a probability of 5–30%. One-third of neurons generated spontaneous discharges and provided a background of intrinsic activity to the network. The heterogeneity and random coupling of these neurons maintained this background activity asynchronous. Refractoriness was modeled either by use-dependent synaptic depression or by cellular afterhyperpolarization. In both cases, the recruitment of neurons into spontaneous synchronized discharges was determined by the interplay of refractory mechanisms with stochastic fluctuations in background activity. Subgroups of easily recruitable neurons served as amplifiers of these fluctuations, thereby initiating a cascade-like recruitment of neurons (“avalanche effect”). In contrast, timing depended on the precise implementation of neuronal refractoriness and synaptic connectivity. With synaptic depression, neuronal synchronization always occurred stochastically, whereas with cellular afterhyperpolarization, stochastic turned into periodic behavior with increasing synaptic strength. These results associate the type of refractory mechanism with the temporal statistics and the mechanism of synchronization, thereby providing a framework for differentiating between cellular mechanisms of spontaneous rhythmogenesis.
Distance-Dependent Modifiable Threshold for Action Potential Back-Propagation in Hippocampal Dendrites
Authors: Bernard C. , Johnston D.
Published: May 2006

In hippocampal CA1 pyramidal neurons, action potentials generated in the axon back-propagate in a decremental fashion into the dendritic tree where they affect synaptic integration and synaptic plasticity. The amplitude of back-propagating action potentials (b-APs) is controlled by various biological factors, including membrane potential ( Vm). We report that, at any dendritic location ( x), the transition from weak (small-amplitude b-APs) to strong (large-amplitude b-APs) back-propagation occurs when Vm crosses a threshold potential, θ x. When Vm > θ x, back-propagation is strong (mostly active). Conversely, when Vm < θ x, back-propagation is weak (mostly passive). θ x varies linearly with the distance ( x) from the soma. Close to the soma, θ x ≪ resting membrane potential (RMP) and a strong hyperpolarization of the membrane is necessary to switch back-propagation from strong to weak. In the distal dendrites, θ x ≫ RMP and a strong depolarization is necessary to switch back-propagation from weak to strong. At ∼260 μm from the soma, θ260 ≈ RMP, suggesting that in this dendritic region back-propagation starts to switch from strong to weak. θ x depends on the availability or state of Na+ and K+ channels. Partial blockade or phosphorylation of K+ channels decreases θ x and thereby increases the portion of the dendritic tree experiencing strong back-propagation. Partial blockade or inactivation of Na+ channels has the opposite effect. We conclude that θ x is a parameter that captures the onset of the transition from weak to strong back-propagation. Its modification may alter dendritic function under physiological and pathological conditions by changing how far large action potentials back-propagate in the dendritic tree.
Neocortical Pyramidal Cells Respond as Integrate-and-Fire Neurons to In Vivo–Like Input Currents
Authors: Rauch Alexander , La Camera Giancarlo , Lüscher Hans-Rudolf , Senn Walter , Fusi Stefano
Published: May 2006

In the intact brain neurons are constantly exposed to intense synaptic activity. This heavy barrage of excitatory and inhibitory inputs was recreated in vitro by injecting a noisy current, generated as an Ornstein–Uhlenbeck process, into the soma of rat neocortical pyramidal cells. The response to such in vivo–like currents was studied systematically by analyzing the time development of the instantaneous spike frequency, and when possible, the stationary mean spike frequency as a function of both the mean and the variance of the input current. All cells responded with an in vivo–like action potential activity with stationary statistics that could be sustained throughout long stimulation intervals (tens of seconds), provided the frequencies were not too high. The temporal evolution of the response revealed the presence of mechanisms of fast and slow spike frequency adaptation, and a medium duration mechanism of facilitation. For strong input currents, the slow adaptation mechanism made the spike frequency response nonstationary. The minimal frequencies that caused strong slow adaptation (a decrease in the spike rate by more than 1 Hz/s), were in the range 30–80 Hz and depended on the pipette solution used. The stationary response function has been fitted by two simple models of integrate-and-fire neurons endowed with a frequency-dependent modification of the input current. This accounts for all the fast and slow mechanisms of adaptation and facilitation that determine the stationary response, and proved necessary to fit the model to the experimental data. The coefficient of variability of the interspike interval was also in part captured by the model neurons, by tuning the parameters of the model to match the mean spike frequencies only. We conclude that the integrate-and-fire model with spike-frequency–dependent adaptation/facilitation is an adequate model reduction of cortical cells when the mean spike-frequency response to in vivo–like currents with stationary statistics is considered.