Theoretical foundations of the sound analog membrane potential that underlies coincidence detection in the barn owl

A wide variety of neurons encode temporal information via phase-locked spikes. In the avian auditory brainstem, neurons in the cochlear nucleus magnocellularis (NM) send phase-locked synaptic inputs to coincidence detector neurons in the nucleus laminaris (NL) that mediate sound localization. Previous modeling studies suggested that converging phase-locked synaptic inputs may give rise to a periodic oscillation in the membrane potential of their target neuron. Recent physiological recordings in vivo revealed that owl NL neurons changed their spike rates almost linearly with the amplitude of this oscillatory potential. The oscillatory potential was termed the sound analog potential, because of its resemblance to the waveform of the stimulus tone. The amplitude of the sound analog potential recorded in NL varied systematically with the interaural time difference (ITD), which is one of the most important cues for sound localization. In order to investigate the mechanisms underlying ITD computation in the NM-NL circuit, we provide detailed theoretical descriptions of how phase-locked inputs form oscillating membrane potentials. We derive analytical expressions that relate presynaptic, synaptic, and postsynaptic factors to the signal and noise components of the oscillation in both the synaptic conductance and the membrane potential. Numerical simulations demonstrate the validity of the theoretical formulations for the entire frequency ranges tested (1–8 kHz) and potential effects of higher harmonics on NL neurons with low best frequencies (<2 kHz)

Biophysical basis of the sound analog membrane potential that underlies coincidence detection in the barn owl

Interaural time difference (ITD), or the difference in timing of a sound wave arriving at the two ears, is a fundamental cue for sound localization. A wide variety of animals have specialized neural circuits dedicated to the computation of ITDs. In the avian auditory brainstem, ITDs are encoded as the spike rates in the coincidence detector neurons of the nucleus laminaris (NL). NL neurons compare the binaural phase-locked inputs from the axons of ipsi- and contralateral nucleus magnocellularis (NM) neurons. Intracellular recordings from the barn owl's NL in vivo showed that tonal stimuli induce oscillations in the membrane potential. Since this oscillatory potential resembled the stimulus sound waveform, it was named the sound analog potential (Funabiki et al., 2011). Previous modeling studies suggested that a convergence of phase-locked spikes from NM leads to an oscillatory membrane potential in NL, but how presynaptic, synaptic, and postsynaptic factors affect the formation of the sound analog potential remains to be investigated. In the accompanying paper, we derive analytical relations between these parameters and the signal and noise components of the oscillation. In this paper, we focus on the effects of the number of presynaptic NM fibers, the mean firing rate of these fibers, their average degree of phase-locking, and the synaptic time scale. Theoretical analyses and numerical simulations show that, provided the total synaptic input is kept constant, changes in the number and spike rate of NM fibers alter the ITD-independent noise whereas the degree of phase-locking is linearly converted to the ITD-dependent signal component of the sound analog potential. The synaptic time constant affects the signal more prominently than the noise, making faster synaptic input more suitable for effective ITD computation

Catheter Interventions for Acute Deep Venous Thrombosis: Who, When and How

Deep venous thrombosis (DVT) is common and can be a source of morbidity by way of pulmonary embolism and post-thrombotic syndrome. Recent trials have demonstrated both early and late symptomatic benefit in venous thrombolysis and early recanalisation of the iliocaval system of selected patients. Based on the emerging evidence, national societies have published guidelines that recommend early thrombus removal in iliofemoral DVT in patients with low bleeding risk and good life expectancy. In light of these recommendations, endovenous thrombolysis and/or thrombectomy have become more popular among vein specialists. As more venous technology becomes available, surgeons and interventionalists should take pause and ensure their patient selection and treatment algorithms parallel that of existing and emerging evidence. This article summarises current evidence, technology, and the approach used at a high-volume academic centre in treating iliofemoral DVT

How to prevent viremia rebound? Evidence from a PRRSv data-supported model of immune response Natacha Go1,2,3*, Suzanne Touzeau

International audienceBACKGROUNDUnderstanding what determines the between-host variability in infection dynamics is a key issue to better control the infection spread. In particular, pathogen clearance is desirable over rebounds for the health of the infected individual and its contact group. In this context, the Porcine Respiratory and Reproductive Syndrome virus (PRRSv) is of particular interest. Numerous studies have shown that pigs similarly infected with this highly ubiquitous virus elicit diverse response profiles. Whilst some manage to clear the virus within a few weeks, others experience prolonged infection with a rebound. Despite much speculation, the underlying mechanisms responsible for this undesirable rebound phenomenon remain unclear.RESULTSWe aimed at identifying immune mechanisms that can reproduce and explain the rebound patterns observed in PRRSv infection using a mathematical modelling approach of the within-host dynamics. As diverse mechanisms were found to influence PRRSv infection, we established a model that details the major mechanisms and their regulations at the between-cell scale. We developed an ABC-like optimisation method to fit our model to an extensive set of experimental data, consisting of non-rebounder and rebounder viremia profiles. We compared, between both profiles, the estimated parameter values, the resulting immune dynamics and the efficacies of the underlying immune mechanisms. Exploring the influence of these mechanisms, we showed that rebound was promoted by high apoptosis, high cell infection and low cytolysis by Cytotoxic T Lymphocytes, while increasing neutralisation was very efficient to prevent rebounds.CONCLUSIONSOur paper provides an original model of the immune response and an appropriate systematic fitting method, whose interest extends beyond PRRS infection. It gives the first mechanistic explanation for emergence of rebounds during PRRSv infection. Moreover, results suggest that vaccines or genetic selection promoting strong neutralising and cytolytic responses, ideally associated with low apoptotic activity and cell permissiveness, would prevent rebound

Activity of Nitazoxanide Against Viral Gastroenteritis: A Systematic Review

Introduction: Nitazoxanide is an oral anti-parasitic agent that has been found to have broad antiviral activity. Its role in the treatment of viral gastroenteritis is not well-studied. Given the worldwide prevalence of viral gastroenteritis, particularly in developing nations, a systematic review of this topic would be valuable. Methods: A formal literature search with the assistance of a reference librarian included randomized controlled trials, cohort studies, case-control studies, and case reports. Studies were included if they pertained to nitazoxanide use for viral gastroenteritis and excluded if nitazoxanide was used for parasitic or other viral illnesses. Results: Based on inclusion and exclusion criteria, 5 randomized controlled trials (2 in Egypt and 1 each in Peru, India, and Bolivia) were included in the systematic review. Four of the studies enrolled children only; one study included adults. All studies noted a statistically significant reduction in time from the first dose of nitazoxanide to resolution of illness (approximately one to 2 days) in patients compared to the receiving placebos (approximately 3 days). There were 9 case series or reports on nitazoxanide use for viral gastroenteritis in immunocompromised hosts; of these, only one case reported a noticeable effect of nitazoxanide in reducing symptom duration and severity. Conclusion: Despite the limited number of studies and the potential risk of bias introduced by the funding source, a benefit of nitazoxanide in reducing duration of illness from viral gastroenteritis was demonstrated for immunocompetent children. Randomized controlled trials are needed to elucidate the role of nitazoxanide for treating viral gastroenteritis in immunocompromised hosts

Genetic and Transmission Analysis of Helicobacter pylori Strains within a Family1

Point mutations, intragenic recombination, and introduction of foreign alleles enhanced strain diversity within the family

Trends in Incidence of Hospitalized Acute Myocardial Infarction in the Cardiovascular Research Network (CVRN)

Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations

Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered mental status

The authors present a case of a 56-year-old man with altered mental status. Magnetic resonance imaging (MRI) of the brain revealed non-enhancing abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum. Immunohistochemisty demonstrated precursor T-cell lymphoblastic lymphoma. After treatment with methotrexate, he improved clinically without focal sensorimotor deficits and with improving orientation. MRI showed almost complete resolution of brainstem and cerebral lesions. To the authors’ knowledge, there are only five previous reports of primary central nervous system T-cell lymphoblastic lymphoma. Since treatable, it deserves consideration in patients with altered mental status and imaging abnormalities that include diffuse, non-enhancing changes with increased signal on T2-weighted images