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In JoVE (1)
- Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals
Other Publications (29)
- The European Journal of Neuroscience
- Journal of Muscle Research and Cell Motility
- The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
- Journal of Physiology, Paris
- The European Journal of Neuroscience
- Neural Networks : the Official Journal of the International Neural Network Society
- Journal of Medical Case Reports
- Forensic Science International
- Journal of Inorganic Biochemistry
- Journal of Neurophysiology
- Journal of Physiology, Paris
- Advances in Experimental Medicine and Biology
- Trends in Neurosciences
- IDrugs : the Investigational Drugs Journal
- PloS One
- Journal of Structural Biology
- Journal of Neurophysiology
- Journal of Cardiovascular Electrophysiology
- Journal of Electrocardiology
- Biochemical and Biophysical Research Communications
- Veterinary Microbiology
- American Journal of Physiology. Heart and Circulatory Physiology
- Pflügers Archiv : European Journal of Physiology
- American Journal of Physiology. Heart and Circulatory Physiology
- Current Biology : CB
- Postgraduate Medicine
- Veterinary Research
- Frontiers in Neural Circuits
Articles by Claire Martin in JoVE
Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals
Romain Chery, Barbara L'Heureux, Mounir Bendahmane, Rémi Renaud, Claire Martin, Frédéric Pain, Hirac Gurden
Laboratoire d’Imagerie et de Modélisation en Neurobiologie et Cancérologie, UMR8165 Université Paris Sud 11, Paris Diderot 7 – CNRS
This article presents the protocols of intrinsic optical signals and flavoproteins autofluorescence signals imaging to map odor-evoked activities at the surface of the olfactory bulb in mice.
Other articles by Claire Martin on PubMed
Olfactory Learning Modifies the Expression of Odour-induced Oscillatory Responses in the Gamma (60-90 Hz) and Beta (15-40 Hz) Bands in the Rat Olfactory Bulb
The European Journal of Neuroscience. Jan, 2003 | Pubmed ID: 12542672
This study addressed the question of the possible functional relevance of two different oscillatory activities, beta and gamma (15-40 and 60-90 Hz, respectively) for perception and memory processes in olfactory areas of mammals. Local field potentials were recorded near relay olfactory bulb neurons while rats performed an olfactory discrimination task. Signals reflected the mass activity from this region and characteristics of oscillatory activities were used as an index of local synchrony. Beta and gamma oscillatory activities were quantified by time-frequency methods before during and after odour sampling. In rats early in their training, olfactory sampling was associated with a significant decrease in power in the gamma band in parallel with a weak but significant increase in the beta band (centred on 27 Hz). Several days later, in well-trained rats, the gamma oscillatory depression was significantly enhanced both in duration and amplitude. It appeared within the 500 ms time period preceding odour onset and was further reduced during the odour period. Concurrently the beta oscillatory response (now centred on 24 Hz) during odour sampling was amplified by a twofold factor. The beta band response was modulated according to the chemical nature of the stimuli and rat's behavioural response. This study showed for the first time that odour sampling in behaving animals is associated with a clear shift in the olfactory bulb neuronal activity from a gamma to a beta oscillatory regime. Moreover, the data stress the importance of studying the odour-induced beta activity and its relation to perception and memory.
Journal of Muscle Research and Cell Motility. 2003 | Pubmed ID: 14677643
Ultrastructural features of tubular-sarcoplasmic (T-SR) triad junctions and measures of cell volume following graded increases of extracellular tonicity were compared under physiological conditions recently shown to produce spontaneous release of intracellularly stored Ca2+ in fully polarized amphibian skeletal muscle fibres. The fibres were fixed using solutions of equivalent tonicities prior to processing for electron microscopy. The resulting anatomical sections demonstrated a partially reversible cell shrinkage corresponding to substantial increases in intracellular solute or ionic strength graded with extracellular tonicity. Serial thin sections through triad structures confirmed the presence of geometrically close but anatomically isolated transverse (T-) tubular and sarcoplasmic reticular (SR) membranes contrary to earlier suggestions for the development of luminal continuities between these structures in hypertonic solutions. They also quantitatively demonstrated accompanying decreases in T-SR distances, increased numbers of sections that showed closely apposed T and SR membranes, tubular luminal swelling and reductions in luminal volume of the junctional SR, all correlated with the imposed increases in extracellular osmolarity. Fully polarized fibres correspondingly showed elementary Ca(2+)-release events ('sparks', in 100 mM-sucrose-Ringer solution), sustained Ca2+ elevations and propagated Ca2+ waves (> or = 350-500 mM sucrose) following exposure to physiological Ringer solutions of successively greater tonicities. These were absent in hypotonic, isotonic or less strongly hypertonic (approximately 50 mM sucrose-Ringer) solutions. Yet exposure to hypotonic solutions also disrupted T-SR junctional anatomy. It increased the tubular diameters and T-SR distances and reduced their area of potential contact. The spontaneous release of intracellularly stored Ca2+ thus appears more closely to correlate with the expected changes in intracellular solute strength or a reduction in absolute T-SR distance rather than disruption of an optimal anatomical relationship between T and SR membranes taking place with either increases or decreases in extracellular tonicity.
Learning Modulation of Odor-induced Oscillatory Responses in the Rat Olfactory Bulb: a Correlate of Odor Recognition?
The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Jan, 2004 | Pubmed ID: 14724237
In the first relay of information processing, the olfactory bulb (OB), odors are known to generate specific spatial patterns of activity. Recently, in freely behaving rats, we demonstrated that learning modulated oscillatory activity in local field potential (LFP), in response to odors, in both beta (15-40 Hz) and gamma (60-90 Hz) bands. The present study further characterized this odor-induced oscillatory activity with emphasis on its spatiotemporal distribution over the olfactory bulb and on its relationship with improvement of behavioral performances along training. For that purpose, LFPs were simultaneously recorded from four locations in the OB in freely moving rats performing an olfactory discrimination task. Electrodes were chronically implanted near relay neurons in the mitral cell body layer. Time-frequency methods were used to extract signal characteristics (amplitude, frequency, and time course) in the two frequency bands. Before training, odor presentation produced, on each site, a power decrease in gamma oscillations and a weak but significant increase in power of beta oscillations (approximately 25 Hz). When the training was achieved, these two phenomena were amplified. Interestingly, the beta oscillatory response showed several significant differences between the anterodorsal and posteroventral regions of the OB. In addition, clear-cut beta responses occurred in the signal as soon as animals began to master the task. As a whole, our results point to the possible functional importance of beta oscillatory activity in the mammalian OB, particularly in the context of olfactory learning.
Learning-induced Modulation of Oscillatory Activities in the Mammalian Olfactory System: the Role of the Centrifugal Fibres
Journal of Physiology, Paris. Jul-Nov, 2004 | Pubmed ID: 16274975
In the mammalian olfactory system, oscillations related to odour representation have been described in field potential activities. Previous results showed that in olfactory bulb (OB) of awake rats engaged in an olfactory learning, odour presentation produced a decrease of oscillations in gamma frequency range (60-90 Hz) associated with a power increase in beta frequency range (15-40 Hz). This response pattern was strongly amplified in trained animals. The aim of this work was twofold: whether learning also induces similar changes in OB target structures and whether such OB response depends on its centrifugal inputs. Local field potentials (LFPs) were recorded through chronically implanted electrodes in the OB, piriform and enthorhinal cortices of freely moving rats performing an olfactory discrimination. Oscillatory activities characteristics (amplitude, frequency and time-course) were extracted in beta and gamma range by a wavelet analysis. First, we found that odour induced beta oscillatory activity was present not only in the OB, but also in the other olfactory structures. In each recording site, characteristics of the beta oscillatory responses were dependent of odour, structure and learning level. Unilateral section of the olfactory peduncle was made before training, and LFPs were symmetrically recorded in the two bulbs all along the acquisition of the learning task. Data showed that deprivation of centrifugal feedback led to an increase of spontaneous gamma activity. Moreover, under this condition olfactory learning was no longer associated with the typical large beta band. As a whole, learning modulation of the beta oscillatory response in olfactory structures may reflect activity of a distributed functional network involved in odour representation.
The European Journal of Neuroscience. Apr, 2006 | Pubmed ID: 16623837
In trained behaving rats, the expression of a prominent beta oscillatory activity in the olfactory system was previously identified as a correlate of odour recognition. The aim of the present study was to assess the putative role of a functional coupling between the olfactory bulb (OB) and higher structures in this activity. We performed a unilateral inactivation of the medial part of the olfactory peduncle by lidocaine infusion. Inactivation deprived the OB from most of its centrifugal afferences, including feedback connections from the piriform cortex (PC) while sparing the ascending fibres from the OB to higher cortical structures. This treatment reduced the amplitude of odour-induced oscillatory beta responses both in OB and PC. In parallel, gamma activity classically observed in these two structures during spontaneous activity displayed a strong enhancement. Results suggest that odour-induced oscillatory response could be the emergent feature of an olfactory functional network set up through learning.
Neuron. Aug, 2006 | Pubmed ID: 16880120
In this issue of Neuron, Rinberg et al. show that mice use a speed-accuracy tradeoff in odor discrimination. Shorter sampling results in high performance for easy problems, and enforced longer sampling results in higher accuracy for difficult problems, but mice freely choose intermediate sampling durations and accuracy varies with difficulty. Reward value and task requirements may determine sampling time choice and performance levels.
A Machine Learning Approach to the Analysis of Time-frequency Maps, and Its Application to Neural Dynamics
Neural Networks : the Official Journal of the International Neural Network Society. Mar, 2007 | Pubmed ID: 17145165
The statistical analysis of experimentally recorded brain activity patterns may require comparisons between large sets of complex signals in order to find meaningful similarities and differences between signals with large variability. High-level representations such as time-frequency maps convey a wealth of useful information, but they involve a large number of parameters that make statistical investigations of many signals difficult at present. In this paper, we describe a method that performs drastic reduction in the complexity of time-frequency representations through a modelling of the maps by elementary functions. The method is validated on artificial signals and subsequently applied to electrophysiological brain signals (local field potential) recorded from the olfactory bulb of rats while they are trained to recognize odours. From hundreds of experimental recordings, reproducible time-frequency events are detected, and relevant features are extracted, which allow further information processing, such as automatic classification.
Femoral Vein Thrombophlebitis and Septic Pulmonary Embolism Due to a Mixed Anaerobic Infection Including Solobacterium Moorei: a Case Report
Journal of Medical Case Reports. 2007 | Pubmed ID: 17605768
Primary foci of necrobacillosis infection outside the head and neck are uncommon but have been reported in the urogenital or gastrointestinal tracts. Reports of infection with Solobacterium moorei are rare.
Simultaneous Analysis of Six Amphetamines and Analogues in Hair, Blood and Urine by LC-ESI-MS/MS. Application to the Determination of MDMA After Low Ecstasy Intake
Forensic Science International. Aug, 2007 | Pubmed ID: 17629643
A rapid and sensitive method using LC-MS/MS triple stage quadrupole for the determination of traces of amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), 3,4-methylenedioxyethamphetamine (MDEA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair, blood and urine has been developed and validated. Chromatography was carried out on an Uptisphere ODB C(18) 5 microm, 2.1 mm x 150 mm column (Interchim, France) with a gradient of acetonitrile and formate 2 mM pH 3.0 buffer. Urine and blood were extracted with Toxitube A (Varian, France). Segmented scalp hair was treated by incubation 15 min at 80 degrees C in NaOH 1M before liquid-liquid extraction with hexane/ethyl acetate (2/1, v/v). The limits of quantification (LOQ) in blood and urine were at 0.1 ng/mL for all analytes. In hair, LOQ was <5 pg/mg for MA, MDMA, MDEA and MBDB, at 14.7 pg/mg for AP and 15.7 pg/mg for MDA. Calibration curves were linear in the range 0.1-50 ng/mL in blood and urine; in the range 5-500 pg/mg for MA, MDMA, MDEA and MBDB, and 20-500 pg/mg for AP and MDA. Inter-day precisions were <13% for all analytes in all matrices. Accuracy was <20% in blood and urine at 1 and 50 ng/mL and <10% in hair at 20 and 250 pg/mg. This method was applied to the determination of MDMA in a forensic case of single administration of ecstasy to a 16-year-old female without her knowledge during a party. She suffered from hyperactivity, sweating and agitation. A first sample of urine was collected a few hours after (T+12h) and tested positive to amphetamines by immunoassay by a clinical laboratory. Blood and urine were sampled for forensic purposes at day 8 (D+8) and scalp hair at day 60 (D+60). No MDMA was detected in blood, but urine and hair were tested positive, respectively at 0.42 ng/mL and at 22 pg/mg in hair only in the segment corresponding to the period of the offence, while no MDA was detectable. This method allows the detection of MDMA up to 8 days in urine after single intake.
Journal of Inorganic Biochemistry. Sep, 2007 | Pubmed ID: 17629949
Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.
Journal of Neurophysiology. Oct, 2007 | Pubmed ID: 17699692
Several studies have shown that memory consolidation relies partly on interactions between sensory and limbic areas. The functional loop formed by the olfactory system and the hippocampus represents an experimentally tractable model that can provide insight into this question. It had been shown previously that odor-learning associated beta band oscillations (15-30 Hz) of the local field potential in the rat olfactory system are enhanced with criterion performance, but it was unknown if these involve networks beyond the olfactory system. We recorded local field potentials from the olfactory bulb (OB) and dorsal and ventral hippocampus during acquisition of odor discriminations in a go/no-go task. These regions showed increased beta oscillation power during odor sampling, accompanied by a coherence increase in this frequency band between the OB and both hippocampal subfields. This coherence between the OB and the hippocampus increased with the onset of the first rule transfer to a new odor set and remained high for all learning phases and subsequent odor sets. However, coherence between the two hippocampal fields reset to baseline levels with each new odor set and increased again with criterion performance. These data support hippocampal involvement in the network underlying odor-discrimination learning and also suggest that cooperation between the dorsal and ventral hippocampus varies with learning progress. Oscillatory activity in the beta range may thus provide a mechanism by which these areas are linked during memory consolidation, similar to proposed roles of beta oscillations in other systems with long-range connections.
Journal of Physiology, Paris. Jan-May, 2007 | Pubmed ID: 18054211
Electrophysiological recordings performed in the mammalian olfactory bulb (OB) aimed at deciphering neural rules supporting neural representation of odors. In spite of a fairly large number of available data, no clear picture emerges yet in the mammalian OB. This paper summarizes some important findings and underlines the fact that difference in experimental conditions still represents a major limitation to the emergence of a synthetic view. More specifically, we examine to what extent the absence or the presence of anaesthetic influence OB neuronal responsiveness. In addition, we will see that recordings of either single cell activity or populational activity provide quite different pictures. As a result some experimental approaches provide data underlying sensory properties of OB neurons while others emphasize their capabilities of integrating incoming sensory information with attention, motivation and previous experience.
Advances in Experimental Medicine and Biology. 2008 | Pubmed ID: 19209823
Cytoskeletal tropomyosin (Tm) isoforms show extensive intracellular sorting, resulting in spatially distinct actin-filament populations. Sorting of Tm isoforms has been observed in a number of cell types, including fibroblasts, epithelial cells, osteoclasts, neurons and muscle cells. Different Tm isoforms have differential impact on the activity of a number of actin-binding proteins and can therefore differentially regulate actin filament function. Functionally distinct sub-populations of actin filaments can therefore be defined on the basis of the Tm isoforms associated with the filaments. The mechanisms that underlie Tm sorting are not yet well understood, but it is clear that Tm sorting is a very fluid and dynamic process, with changes in sorting occurring throughout development and cell differentiation. For this reason, it is unlikely that Tm localization is determined by an intrinsic sorting signal that directs particular isoforms to a single geographical location. Rather, a molecular sink model where isoforms accumulate in actin-based structures where they have the highest affinity, is most consistent with current data. This model would predict Tm sorting to be influenced by changes to actin filament dynamics and organization and collaboration with other actin-binding proteins.
Trends in Neurosciences. Apr, 2009 | Pubmed ID: 19243843
Olfactory system oscillations play out with beautiful temporal and behavioral regularity on the oscilloscope and seem to scream 'meaning'. Always there is the fear that, although attractive, these symbols of dynamic regularity might be just seductive epiphenomena. There are now many studies that have isolated some of the neural mechanisms involved in these oscillations, and recent work argues that they are functional and even necessary at the physiological and cognitive levels. However, much remains to be done for a full understanding of their functions.
Recent Developments in Wound Management: Intelligent Biomaterials to Novel Antimicrobials. 24 September 2009, London, UK
IDrugs : the Investigational Drugs Journal. Nov, 2009 | Pubmed ID: 19844855
The Recent Developments in Wound Management conference, held in London, included topics covering new developments in the field of wound treatment, relating to infection management. This conference report highlights selected presentations on the prevalence of pathogenic microorganisms, and the development of anti-infective biomaterials, antimicrobial biocides and novel types of antimicrobial agents.
PloS One. 2009 | Pubmed ID: 19956567
Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival.
Alternatively Spliced N-terminal Exons in Tropomyosin Isoforms Do Not Act As Autonomous Targeting Signals
Journal of Structural Biology. May, 2010 | Pubmed ID: 20026406
Tropomyosin (Tm) polymerises head-to-tail to form a continuous polymer located in the major groove of the actin filament. Multiple Tm isoforms are generated by alternative splicing of four genes, and individual isoforms show specific localisation patterns in many cell types, and can have differing effects on the actin cytoskeleton. Fluorescently-tagged Tm isoforms and mutants were expressed in C2C12 cells to investigate the mechanisms of alternative localisation of high molecular weight (HMW) and low molecular weight (LMW) Tms. Fluorescently-tagged Tm constructs show similar localisation to endogenous Tms as observed by antibodies, with the HMW Tm3 relatively diminished at the periphery of cells compared to LMW isoforms Tm5b or Tm5NM1. Tm3 and Tm5b only differ in their N-terminal exons, but these N-terminal exons do not independently direct localisation within the cell, as chimeric mutants Tm3-Tm5NM1 and Tm5b-Tm5NM1 show an increased peripheral localisation similar to Tm5NM1. The lower abundance of Tm3 at the periphery of the cell is not a result of different protein dynamics, as Tm3 and Tm5b show similar recovery after photobleaching. The relative exclusion of Tm3 from the periphery of cells does, however, require interaction with the actin filament, as mutants with truncations at either the N-terminus or the C-terminus are unable to localise to actin stress fibres, and are present in the most peripheral regions of the cell. We conclude that it is the entire Tm molecule which is the unit of sorting, and that the alternatively spliced N-terminal exons do not act as autonomous targeting signals.
Directional Coupling from the Olfactory Bulb to the Hippocampus During a Go/no-go Odor Discrimination Task
Journal of Neurophysiology. May, 2010 | Pubmed ID: 20164392
The hippocampus and olfactory regions are anatomically close, and both play a major role in memory formation. However, the way they interact during odor processing is still unclear. In both areas, strong oscillations of the local field potential (LFP) can be recorded, and are modulated by behavior. In particular, in the olfactory system, the beta rhythm (15-35 Hz) is associated with cognitive processing of an olfactory stimulus. Using LFP recordings in the olfactory bulb and dorsal and ventral hippocampus during performance of an olfactory go/no-go task in rats, we previously showed that beta oscillations are also present in the hippocampus, coherent with those in the olfactory bulb, during odor sampling. In this study, we provide further insight into information transfer in the olfacto-hippocampal network by using directional coherence (DCOH estimate), a method based on the temporal relation between two or more signals in the frequency domain. In the theta band (6-12 Hz), coherence between the olfactory bulb (OB) and the hippocampus (HPC) is weak and can be both in the feedback and feedforward directions. However, at this frequency, modulation of the coupling between the dorsal and ventral hippocampus is seen during stimulus expectation versus odor processing. In the beta frequency band (15-35 Hz), analysis showed a strong unidirectional coupling from the OB to dorsal and ventral HPC, indicating that, during odor processing, beta oscillations in the hippocampus are driven by the olfactory bulb.
Increased Right Ventricular Repolarization Gradients Promote Arrhythmogenesis in a Murine Model of Brugada Syndrome
Journal of Cardiovascular Electrophysiology. Oct, 2010 | Pubmed ID: 20384647
Brugada syndrome (BrS) is associated with loss of Na(+) channel function and increased risks of a ventricular tachycardia exacerbated by flecainide but reduced by quinidine. Previous studies in nongenetic models have implicated both altered conduction times and repolarization gradients in this arrhythmogenicity. We compared activation latencies and spatial differences in action potential recovery between different ventricular regions in a murine Scn5a+/- BrS model, and investigated the effect of flecainide and quinidine upon these.
In Vivo Studies of Scn5a+/- Mice Modeling Brugada Syndrome Demonstrate Both Conduction and Repolarization Abnormalities
Journal of Electrocardiology. Sep-Oct, 2010 | Pubmed ID: 20638671
We investigate the extent to which the electrocardiographic (ECG) properties of intact Scn5a+/- mice reproduce the corresponding clinical Brugada syndrome phenotype and use this model to investigate the role of conduction and repolarization abnormalities in the arrhythmogenic mechanism.
Biochemical and Biophysical Research Communications. Jan, 2010 | Pubmed ID: 19932089
Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relied on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists could block SphK1 stimulation by DHT and its consequences. Finally, SphK1 inhibition not only abrogated DHT-induced ERK activation but also blocked cell proliferation, while ERK inhibition had no impact, suggesting that SphK1 was critical for DHT signaling yet independently of the ERK.
Veterinary Microbiology. Jan, 2011 | Pubmed ID: 20709472
Inter-species transmission is often incriminated in the epidemiology of Pestivirus diseases. The purpose of this study was to investigate the prevalence of Pestivirus in some mountain wild ungulates and to determine their role in Pestivirus transmission, as mountain pastures are a place where cohabitations between wild and domestic ungulates are particularly high. Between 2003 and 2007, a longitudinal epidemiological study was carried out on hunted ungulates in the French Hautes-Alpes department. Pestivirus-specific antibodies against p80 protein (also named NS3) common to all Bovine Viral Diarrhea Virus (BVDV) and Border Disease Virus (BDV) were found in 45.9% (95% confidence interval [CI95%]: 40.5-51.3%) of the 343 tested chamois (Rupicapra rupicapra). In addition, mouflons (Ovis gmelinii musimon) were shown for the first time to be strongly infected (61.1%; CI95%: 38.6-83.6) by a Pestivirus. These serological ELISA results were confirmed by comparative virus neutralization tests, performed on seven Pestivirus strains by using 15 seropositive samples. The highest antibody titers were directed against 2 BDV strains (Av and 33s strains), rather than BDV-4, a strain responsible for Pyrenean-chamois epizooties. Virus neutralization tests confirm a BDV circulation in wild ungulates in the French South Alps. However, no Pestivirus RNA was detected by reverse-transcriptase polymerase chain reaction in serum and spleen samples from seronegative animals and no virus was isolated from those samples either. Efforts should be made to improve the protocol in order to be able to isolate and characterize the local strain. Finally, the oldness (age) and femaleness (gender) increase the risk of seroconversion in chamois.
Spatial and Temporal Heterogeneities Are Localized to the Right Ventricular Outflow Tract in a Heterozygotic Scn5a Mouse Model
American Journal of Physiology. Heart and Circulatory Physiology. Feb, 2011 | Pubmed ID: 21097662
Ventricular tachycardia (VT) in Brugada Syndrome patients often originates in the right ventricular outflow tract (RVOT). We explore the physiological basis for this observation using murine whole heart preparations. Ventricular bipolar electrograms and monophasic action potentials were recorded from seven epicardial positions in Langendorff-perfused wild-type and Scn5a+/- hearts. VT first appeared in the RVOT, implicating it as an arrhythmogenic focus in Scn5a+/- hearts. RVOTs showed the greatest heterogeneity in refractory periods, response latencies, and action potential durations, and the most fractionated electrograms. However, incidences of concordant alternans in dynamic pacing protocol recordings were unaffected by the Scn5a+/- mutation or pharmacological intervention. Conversely, particularly at the RVOT, Scn5a+/- hearts showed earlier and more frequent transitions into discordant alternans. This was accentuated by flecainide, but reduced by quinidine, in parallel with their respective pro- and anti-arrhythmic effects. Discordant alternans preceded all episodes of VT. The RVOT of Scn5a+/- hearts also showed steeper restitution curves, with the diastolic interval at which the gradient equaled one strongly correlating with the diastolic interval at which discordant alternans commenced. We attribute the arrhythmic tendency within the RVOT to the greater spatial heterogeneities in baseline electrophysiological properties. These, in turn, give rise to a tendency to drive concordant alternans phenomena into an arrhythmogenic discordant alternans. Our findings may contribute to future work investigating possible pharmacological treatments for a disease in which the current mainstay of treatment is implantable cardioverter defibrillator implantation.
Pflügers Archiv : European Journal of Physiology. Oct, 2011 | Pubmed ID: 21779762
Accentuated right ventricular (RV) gradients in action potential duration (APD) have been implicated in the arrhythmogenicity observed in Brugada syndrome in studies assuming that ventricular effective refractory periods (VERPs) vary in concert with APDs. The present experiments use a genetically modified mouse model to explore spatial heterogeneities in VERP that in turn might affect conduction velocity, thereby causing arrhythmias. Activation latencies, APDs and VERPs recorded during programmed S1S2 protocols were compared in RV and left ventricular (LV) epicardia and endocardia of Langendorff-perfused wild-type (WT) and Scn5a (+/-) hearts. Scn5a (+/-) and WT hearts showed similar patterns of shorter VERPs in RV than LV epicardia, and in epicardia than endocardia. However, Scn5a (+/-) hearts showed longer VERPs, despite shorter APD(90)s, than WT in all regions examined. The pro- and anti-arrhythmic agents flecainide and quinidine increased regional VERPs despite respectively decreasing and increasing the corresponding APD(90)s particularly in Scn5a (+/-) RV epicardia. In contrast, Scn5a (+/-) hearts showed greater VERP gradients between neighbouring regions, particularly RV transmural gradients, than WT (9.1 ± 1.1 vs. 5.7 ± 0.5 ms, p < 0.05, n = 12). Flecainide increased (to 21 ± 0.9 ms, p < 0.05, n = 6) but quinidine decreased (to 4.5 ± 0.5 ms, p < 0.05, n = 6) these gradients, particularly across the Scn5a (+/-) RV. Finally, Scn5a (+/-) hearts showed greater conduction slowing than WT following S2 stimuli, particularly with flecainide administration. Rather than arrhythmogenesis resulting from increased transmural repolarization gradients in an early, phase 2, reentrant excitation mechanism, the present findings implicate RV VERP gradients in potential reentrant mechanisms involving impulse conduction slowed by partial refractoriness.
American Journal of Physiology. Heart and Circulatory Physiology. May, 2011 | Pubmed ID: 21378142
Two major mechanisms have been postulated for the arrhythmogenic tendency observed in Brugada Syndrome (BrS): delays in conduction or increased heterogeneities in repolarization. We use a contact mapping system to directly investigate the interacting roles of these two mechanisms in arrhythmogenesis using a genetic murine model for BrS for the first time. Electrograms were obtained from a multielectrode recording array placed against the left ventricle and right ventricle (RV) of spontaneously beating Langendorff-perfused wild type (WT) and Scn5a+/- mouse hearts. Scn5a+/- hearts showed activation waves arriving at the epicardial surface consistent with slowed conduction, which was exacerbated in the presence of flecainide. Lines of conduction block across the RV resulting from premature ventricular beats led to the formation of reentrant circuits and polymorphic ventricular tachycardia. WT hearts showed an inverse relationship between activation times and activation recovery intervals measured at the epicardial surface, which resulted in synchronicity of repolarization times. In contrast, Scn5a+/- hearts, despite having smaller mean activation recovery intervals, demonstrated a greater heterogeneity compared with WT. Isochronal maps showed that their normal activation recovery interval gradients at the epicardial surface were disrupted, leading to heterogeneity in repolarization times. We thus directly demonstrate the initiation of arrhythmia in the RV of Scn5a+/- hearts. This occurs as a result of the combination of repolarization heterogeneities leading to lines of conduction block and unidirectional conduction, with conduction slowing allowing the formation of reentrant circuits. The repolarization heterogeneities may also be responsible for the changing pattern of block, leading to the polymorphic character of the resulting ventricular tachycardia.
Current Biology : CB. Apr, 2011 | Pubmed ID: 21458264
Cell migration and morphogenesis are driven by both protrusive and contractile actin filament structures. The assembly mechanisms of lamellipodial and filopodial actin filament arrays, which provide the force for plasma membrane protrusions through actin filament treadmilling, are relatively well understood. In contrast, the mechanisms by which contractile actomyosin arrays such as stress fibers are generated in cells, and how myosin II is specifically recruited to these structures, are not known.
Postgraduate Medicine. Mar, 2011 | Pubmed ID: 21474896
Sudden cardiac death (SCD) due to ventricular tachyarrhythmias is an important cause of mortality in the United States, 4% of which occurs in patients with structurally normal hearts. At least some arrhythmias are caused by ≥ 1 mutation in 1 of the genes that control electrical conduction through the heart by altering calcium homeostasis or depolarization or repolarization gradients in the ventricle. Although SCD may be the first presentation, patients may often present with symptoms of palpitations or hemodynamic compromise, such as dizziness, seizure, or syncope, particularly following exertion. They may also be made aware of possibly having the condition due to symptoms in other family members. The primary care physician is ideally placed to investigate these symptoms, including detailed clinical and family histories and examining the baseline electrocardiogram. In all inherited cardiac death syndromes, first-degree relatives should be referred to a cardiologist, and should undergo testing appropriate for the condition. While management of patients at risk of SCD largely centers on risk stratification and, if necessary, insertion of an implantable cardioverter-defibrillator, there are a number of other treatments being developed. β-Blockers are often very effective in preventing arrhythmic episodes associated with catecholaminergic polymorphic ventricular tachycardia and some subtypes of long QT syndrome. In certain situations, calcium channel blockers may also be used. Quinidine and isoproterenol can be useful in treating Brugada syndrome. Left cervicothoracic stellectomy may occasionally be used in the treatment of long QT syndrome. As the genetic basis of these diseases becomes known, genetic testing is forming an increasingly important part of diagnosis, and gene-specific therapy is an area under investigation.
A Survey of the Transmission of Infectious Diseases/infections Between Wild and Domestic Ungulates in Europe
Veterinary Research. Jan-Feb, 2011 | Pubmed ID: 21635726
ABSTRACT: The domestic animals/wildlife interface is becoming a global issue of growing interest. However, despite studies on wildlife diseases being in expansion, the epidemiological role of wild animals in the transmission of infectious diseases remains unclear most of the time. Multiple diseases affecting livestock have already been identified in wildlife, especially in wild ungulates. The first objective of this paper was to establish a list of infections already reported in European wild ungulates. For each disease/infection, three additional materials develop examples already published, specifying the epidemiological role of the species as assigned by the authors. Furthermore, risk factors associated with interactions between wild and domestic animals and regarding emerging infectious diseases are summarized. Finally, the wildlife surveillance measures implemented in different European countries are presented. New research areas are proposed in order to provide efficient tools to prevent the transmission of diseases between wild ungulates and livestock.
Alteration of Sensory-evoked Metabolic and Oscillatory Activities in the Olfactory Bulb of GLAST-deficient Mice
Frontiers in Neural Circuits. 2012 | Pubmed ID: 22291618
Astrocytes are key cellular elements in both the tripartite synapse and the neurovascular unit. To fulfill this dual role in synaptic activity and metabolism, they express a panel of receptors and transporters that sense glutamate. Among them, the GLT-1 and GLAST transporters are known to regulate extracellular glutamate concentrations at excitatory synapses and consequently modulate glutamate receptor signaling. These major uptake systems are also involved in energy supply to neurons. However, the functional role of GLAST in concurrent regulation of metabolic and neuronal activity is currently unknown. We took advantage of the attractive structural and functional features of the main olfactory bulb to explore the impact of GLAST on sensory information processing while probing both glutamate uptake and neuronal activity in glomeruli and deeper cellular layers, respectively. Using odor-evoked 2-deoxyglucose imaging and local field potential recordings in GLAST knockout mice, we show in vivo that deletion of GLAST alters both glucose uptake and neuronal oscillations in olfactory bulb networks.