Novel circRNA-miRNA-mRNA networks regulated by maternal exercise in fetal hearts of pregestational diabetes.

BACKGROUND: Maternal exercise lowers the incidence of congenital heart defects (CHDs) induced by pregestational diabetes. However, the molecular mechanisms underlying the beneficial effects of maternal exercise remain unclear. The present study aimed to identify circular RNA (circRNA), microRNA (miRNA) and mRNA networks that are regulated by maternal exercise in fetal hearts of pregestational diabetes. METHODS: Pregestational diabetes was induced in adult C57BL/6 female mice by streptozotocin. The expression profiles of circRNAs, miRNAs and mRNAs in E10.5 fetal hearts of offspring of control and diabetic mothers with or without exercise were analyzed using next generation sequencing. circRNA-miRNA-mRNA networks in fetal hearts were mapped and key candidate transcripts were verified by qPCR analysis. RESULTS: Pregestational diabetes dysregulated the expression of 206 circRNAs, 66 miRNAs and 391 mRNAs in fetal hearts. Maternal exercise differentially regulated 188 circRNAs, 57 miRNAs and 506 mRNAs in fetal hearts of offspring of pregestational diabetes. A total of 5 circRNAs, 12 miRNAs, and 28 mRNAs were incorporated into a final maternal exercise-associated regulatory network in fetal hearts of offspring of maternal diabetes. Notably, maternal exercise normalized the dysregulated circ_0003226/circ_0015638/miR-351-5p and circ_0002768/miR-3102-3p.2-3p pairs in fetal hearts of pregestational diabetes. CONCLUSION: Maternal exercise reverses the dysregulated circ_0003226/circ_0015638/miR-351-5p and circ_0002768/miR-3102-3p.2-3p pairs, and partially normalizes circRNA, miRNA, and mRNA expression profiles in fetal hearts of pregestational diabetes. These findings shed new light on the potential mechanisms of the beneficial effects of maternal exercise on the developing heart in diabetic pregnancies.

Are frog calls relatively difficult to locate by mammalian predators?

Frogs call in acoustically dense choruses to attract conspecific females. Their calls can potentially reveal their location to predators, many of which are mammals. However, frogs and mammals have very different acoustic receivers and mechanisms for determining sound source direction. We argue that frog calls may have been selected so that they are harder to locate with the direction-finding mechanisms of mammals. We focus on interaural time delay (ITD) estimation using delay-line coincidence detection (place code), and a binaural excitatory/inhibitory (E/I) ITD mechanism found in mammals with small heads (population code). We identify four "strategies" which frogs may employ to exploit the weaknesses of either mechanism. The first two strategies used by the frog confound delay estimation to increase direction ambiguity using highly periodic calls or narrowband calls. The third strategy relies on using short pulses. The E/I mechanism is susceptible to noise with sounds being pulled to the medial plane when signal-to-noise ratio is low. Together, these three strategies compromise both ongoing and onset determination of location using either mechanism. Finally, frogs call in dense choruses using various means for controlling synchrony, maintaining chorus tenure, and abruptly switching off calling, all of which serve to confound location finding. Of these strategies, only chorusing adversely impacts the localization performance of frogs' acoustic receivers. We illustrate these strategies with an analysis of calls from three different frog species.

A dynamic spike threshold with correlated noise predicts observed patterns of negative interval correlations in neuronal spike trains.

Negative correlations in the sequential evolution of interspike intervals (ISIs) are a signature of memory in neuronal spike-trains. They provide coding benefits including firing-rate stabilization, improved detectability of weak sensory signals, and enhanced transmission of information by improving signal-to-noise ratio. Primary electrosensory afferent spike-trains in weakly electric fish fall into two categories based on the pattern of ISI correlations: non-bursting units have negative correlations which remain negative but decay to zero with increasing lags (Type I ISI correlations), and bursting units have oscillatory (alternating sign) correlation which damp to zero with increasing lags (Type II ISI correlations). Here, we predict and match observed ISI correlations in these afferents using a stochastic dynamic threshold model. We determine the ISI correlation function as a function of an arbitrary discrete noise correlation function [Formula: see text], where k is a multiple of the mean ISI. The function permits forward and inverse calculations of the correlation function. Both types of correlation functions can be generated by adding colored noise to the spike threshold with Type I correlations generated with slow noise and Type II correlations generated with fast noise. A first-order autoregressive (AR) process with a single parameter is sufficient to predict and accurately match both types of afferent ISI correlation functions, with the type being determined by the sign of the AR parameter. The predicted and experimentally observed correlations are in geometric progression. The theory predicts that the limiting sum of ISI correlations is [Formula: see text] yielding a perfect DC-block in the power spectrum of the spike train. Observed ISI correlations from afferents have a limiting sum that is slightly larger at [Formula: see text] ([Formula: see text]). We conclude that the underlying process for generating ISIs may be a simple combination of low-order AR and moving average processes and discuss the results from the perspective of optimal coding.

Maternal nicotine exposure induces congenital heart defects in the offspring of mice.

Maternal cigarette smoking is a risk factor for congenital heart defects (CHDs). Nicotine replacement therapies are often offered to pregnant women following failed attempts of smoking cessation. However, the impact of nicotine on embryonic heart development is not well understood. In the present study, the effects of maternal nicotine exposure (MNE) during pregnancy on foetal heart morphogenesis were studied. Adult female mice were treated with nicotine using subcutaneous osmotic pumps at 0.75 or 1.5 mg/kg/day and subsequently bred with male mice. Our results show that MNE dose-dependently increased CHDs in foetal mice. CHDs included atrial and ventricular septal defects, double outlet right ventricle, unguarded tricuspid orifice, hypoplastic left ventricle, thickened aortic and pulmonary valves, and ventricular hypertrophy. MNE also significantly reduced coronary artery size and vessel abundance in foetal hearts. Moreover, MNE resulted in higher levels of oxidative stress and altered the expression of key cardiogenic regulators in the developing heart. Nicotine exposure reduced epicardial-to-mesenchymal transition in foetal hearts. In conclusion, MNE induces CHDs and coronary artery malformation in mice. These findings provide insight into the adverse outcomes of foetuses by MNE during pregnancy.

Distinct Effects of Ibrutinib and Acalabrutinib on Mouse Atrial and Sinoatrial Node Electrophysiology and Arrhythmogenesis.

Background Ibrutinib and acalabrutinib are Bruton tyrosine kinase inhibitors used in the treatment of B-cell lymphoproliferative disorders. Ibrutinib is associated with new-onset atrial fibrillation. Cases of sinus bradycardia and sinus arrest have also been reported following ibrutinib treatment. Conversely, acalabrutinib is less arrhythmogenic. The basis for these different effects is unclear. Methods and Results The effects of ibrutinib and acalabrutinib on atrial electrophysiology were investigated in anesthetized mice using intracardiac electrophysiology, in isolated atrial preparations using high-resolution optical mapping, and in isolated atrial and sinoatrial node (SAN) myocytes using patch-clamping. Acute delivery of acalabrutinib did not affect atrial fibrillation susceptibility or other measures of atrial electrophysiology in mice in vivo. Optical mapping demonstrates that ibrutinib dose-dependently impaired atrial and SAN conduction and slowed beating rate. Acalabrutinib had no effect on atrial and SAN conduction or beating rate. In isolated atrial myocytes, ibrutinib reduced action potential upstroke velocity and Na+ current. In contrast, acalabrutinib had no effects on atrial myocyte upstroke velocity or Na+ current. Both drugs increased action potential duration, but these effects were smaller for acalabrutinib compared with ibrutinib and occurred by different mechanisms. In SAN myocytes, ibrutinib impaired spontaneous action potential firing by inhibiting the delayed rectifier K+ current, while acalabrutinib had no effects on SAN myocyte action potential firing. Conclusions Ibrutinib and acalabrutinib have distinct effects on atrial electrophysiology and ion channel function that provide insight into the basis for increased atrial fibrillation susceptibility and SAN dysfunction with ibrutinib, but not with acalabrutinib.

Calpain activation mediates microgravity-induced myocardial abnormalities in mice via p38 and ERK1/2 MAPK pathways.

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1 Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47 phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47 phox , and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47 phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47 phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

Advancing the understanding of research during medical education through collaborative learning: the Collaboration of Practitioners and Researchers Seminar Series.

BACKGROUND: The Collaboration of Practitioners and Researchers Seminar Series is student-led program comprised of seminars delivered jointly by medical and graduate students on a topic in medicine of mutual interest to an audience of both medical and graduate students. METHODS: Following its inaugural year in 2016-2017, we evaluated changes in attendees' perceived understanding of translational research through an electronic survey and semi-structured interviews with attendees. RESULTS: Study participants rated their understanding of translational research and comfort with interacting with students from the other program higher following attending seminars. Participants believed that the seminars helped in breaking barriers between medical and graduate students. CONCLUSIONS: We conclude that this seminar series positively impacted attendees' understanding of translational research and attitudes towards collaboration between medical and graduate students. We believe that similar initiatives may be of value in fostering new opportunities for collaboration between medical and graduate students at other institutions.

Eliminating the effects of motion during radiofrequency lesion delivery using a novel contact-force controller.

INTRODUCTION: Catheter-tissue contact force is a determinant of radiofrequency (RF) ablation lesion effectiveness. However, ablation on a beating heart is subject to force variability, making it difficult to optimally deliver consistently durable and transmural lesions. This work evaluates improvements in contact force stability and lesion reproducibility by using a catheter contact-force controller (CFC) during lesion delivery in vitro and in vivo. METHODS AND RESULTS: Using a sheath and force-sensing catheter, an experienced operator attempted to maintain a constant force of 20 g at targets within the atria and left ventricle of a pig manually and using the CFC; the average force and contact-force variation (CFV) achieved using each approach were compared. Ablation lesions (20 W, 30 seconds, 17 mL/min irrigation) were created in bovine tissue samples mounted on a platform programmed to reproduce clinically relevant motion. CFC-assisted lesions were delivered to stationary and moving tissue with forces of 5 to 35 g. Mimicking manual intervention, lesions were also delivered to moving tissue while the CFC was disabled. Resultant lesion volumes were compared using two-way analysis of variance. When using the CFC, the average force was within 1 g of the set level, with a CFV less than 5 g, during both in vitro and in vivo experiments. Reproducible and statistically identical (P = .82) lesion volumes proportional to the set force were achieved in both stationary and moving tissue when the CFC was used. CONCLUSIONS: CFC assistance maintains constant force in vivo and removes effect of motion on lesion volume during RF lesion delivery.

Maternal voluntary exercise mitigates oxidative stress and incidence of congenital heart defects in pre-gestational diabetes.

Women with pre-gestational diabetes have a higher risk of producing children with congenital heart defects (CHDs), caused predominantly by hyperglycemia-induced oxidative stress. In this study, we evaluated if exercise during pregnancy could mitigate oxidative stress and reduce the incidence of CHDs in the offspring of diabetic mice. Female mice were treated with streptozotocin to induce pre-gestational diabetes, then mated with healthy males to produce offspring. They were also given access to running wheels 1 week before mating and allowed to exercise voluntarily until E18.5. Heart morphology, gene expression, and oxidative stress were assessed in foetal hearts. Maternal voluntary exercise results in a significantly lower incidence of CHDs from 59.5% to 25%. Additionally, diabetes-induced defects in coronary artery and capillary morphogenesis were also lower with exercise. Myocardial cell proliferation and epithelial-mesenchymal transition at E12.5 was significantly lower with pre-gestational diabetes which was mitigated with maternal exercise. Cardiac gene expression of Notch1, Snail1, Gata4 and Cyclin D1 was significantly higher in the embryos of diabetic mice that exercised compared to the non-exercised group. Furthermore, maternal exercise produced lower reactive oxygen species (ROS) and oxidative stress in the foetal heart. In conclusion, maternal exercise mitigates ROS and oxidative damage in the foetal heart, and results in a lower incidence of CHDs in the offspring of pre-gestational diabetes. Exercise may be an effective intervention to compliment clinical management and further minimize CHD risk in mothers with diabetes.

Over-expression of calpastatin attenuates myocardial injury following myocardial infarction by inhibiting endoplasmic reticulum stress.

BACKGROUND: Ischemic heart injury activates calpains and endoplasmic reticulum (ER) stress in cardiomyocytes. This study investigated whether over-expression of calpastatin, an endogenous calpain inhibitor, protects the heart against myocardial infarction (MI) by inhibiting ER stress. METHODS: Mice over-expressing calpastatin (Tg-CAST) and littermate wild type (WT) mice were divided into four groups: WT-sham, Tg-CAST-sham, WT-MI, and Tg-CAST-MI, respectively. WT-sham and Tg-CAST-sham mice showed similar cardiac function at baseline. MI for 7 days impaired cardiac function in WT-MI mice, which was ameliorated in Tg-CAST-MI mice. RESULTS: Tg-CAST-MI mice exhibited significantly decreased diameter of the left ventricular cavity, scar area, and cardiac cell death compared to WT-MI mice. WT-MI mice had higher cardiac expression of C/EBP homologous protein (CHOP) and BIP, indicators of ER stress, compared to WT-sham mice, indicative of MI-induced ER stress. This increase was abolished in Tg-CAST-MI hearts. Furthermore, administration of tauroursodeoxycholic acid, an inhibitor of ER stress, reduced MI-induced expression of CHOP and BIP, scar area, and myocardial dysfunction. In an in vitro model of oxidative stress, H2O2 stimulation of H9c2 cardiomyoblasts induced calpain activation, CHOP expression, and cell death, all of which were prevented by the calpain inhibitor PD150606, as well as CHOP silencing. CONCLUSIONS: Over-expression of calpastatin ameliorates MI-induced myocardial injury in mice. These protective effects of calpastatin are partially achieved through suppression of the ER stress/CHOP pathway.

Wideband compressive beamforming tomography for drive-by large-scale acoustic source mapping.

Noise-mapping is an effective sound visualization tool for the identification of urban noise hotspots, which is crucial to taking targeted measures to tackle environmental noise pollution. This paper develops a high-resolution wideband acoustic source mapping methodology using a portable microphone array, where the joint localization and power spectrum estimation of individual sources sparsely distributed over a large region are achieved by tomographic imaging with the multi-frequency delay-and-sum beamforming power outputs from multiple array positions. Exploiting the fact that a wideband source has a common spatial signal-support across the frequency spectrum, two-dimensional tomographic maps are produced by applying compressive sensing techniques including group least absolute shrinkage selection operator formulation and sparse Bayesian learning to promote group sparsity over multiple frequency bands. The high-resolution mapping is demonstrated with experimental data recorded with a microphone array mounted atop an electric vehicle driven along a road while playing audio clips from a loudspeaker positioned within the adjacent open field.

Mentoring needs of distributed medical education faculty at a Canadian medical school: a mixed-methods descriptive study.

INTRODUCTION: The Schulich School of Medicine & Dentistry in London, Ontario, has a mentorship program for all full-time faculty. The school would like to expand its outreach to physician faculty located in distributed medical education sites. The purpose of this study was to determine what, if any, mentorship distributed physician faculty currently have, to gauge their interest in expanding the mentorship program to distributed physician faculty and to determine their vision of the most appropriate design of a mentorship program that would address their needs. METHODS: We conducted a mixed-methods study. The quantitative phase consisted of surveys sent to all distributed faculty members that elicited information on basic demographic characteristics and mentorship experiences/needs. The qualitative phase consisted of 4 focus groups of distributed faculty administered in 2 large and 2 small centres in both regions of the school's distributed education network: Sarnia, Leamington, Stratford and Hanover. Interviews were 90 minutes long and involved standardized semistructured questions. RESULTS: Of the 678 surveys sent, 210 (31.0%) were returned. Most respondents (136 [64.8%]) were men, and almost half (96 [45.7%]) were family physicians. Most respondents (197 [93.8%]) were not formal mentors to Schulich faculty, and 178 (84.8%) were not currently being formally mentored. Qualitative analysis suggested that many respondents were involved in informal mentoring. In addition, about half of the respondents (96 [45.7%]) wished to be formally mentored in the future, but they may be inhibited owing to time constraints and geographical isolation. Consistently, respondents wished to have mentoring by a colleague in a similar practice, with the most practical being one-on-one mentoring. CONCLUSION: Our analysis suggests that the school's current formal mentoring program may not be applicable and will require modification to address the needs of distributed faculty.

INTRODUCTION: L'École de médecine et de dentisterie Schulich, à London en Ontario, offre un programme de mentorat à tout le personnel enseignant à temps plein. L'École aimerait étendre son programme aux médecins enseignants des établissements de formation médicale décentralisée. Le but de cette étude était de déterminer à quel mentorat, le cas échéant, ces médecins ont accès actuellement et d'établir leur intérêt pour le programme de mentorat de l'École et leur vision du programme le plus approprié pour répondre à leurs besoins. METHODS: Nous avons mené une étude en méthodologie mixte. Lors de la phase quantitative, nous avons envoyé des questionnaires à tous les médecins des établissements de formation médicale décentralisée afin d'obtenir des renseignements sur les caractéristiques démographiques de base ainsi que les expériences et besoins de mentorat. La phase qualitative comprenait quatre groupes de discussion composés de médecins enseignants décentralisés dans deux grands et deux petits centres des deux régions du réseau de formation décentralisée de l'École, soit Sarnia, Leamington, Stratford et Hanover. Les entrevues étaient d'une durée de 90 minutes et se composaient de questions semi-structurées normalisées. RESULTS: Sur les 678 questionnaires distribués, 210 (31 %) ont été retournés. La plupart des répondants (136 [64,8 %]) étaient des hommes et presque la moitié (96 [45,7 %]) étaient des médecins de famille. La plupart des répondants (197 [93,8 %]) n'agissaient pas comme mentors officiels auprès du personnel enseignant de l'École de médecine et de dentisterie Schulich et 178 (84,8 %) ne recevaient pas de mentorat officiel actuellement. L'analyse qualitative suggère que plusieurs répondants participaient à une forme quelconque de mentorat informel. De plus, environ la moitié des répondants (96 [45,7 %]) souhaitaient recevoir un mentorat officiel à l'avenir, mais avaient possiblement des contraintes liées au manque de temps et à l'isolement géographique. Les répondants ont systématiquement exprimé le désir d'obtenir un mentorat d'un collègue dans une pratique similaire et un mentorat individualisé, de façon pratique. CONCLUSION: Notre analyse suggère que le programme actuel de mentorat de l'École n'est peut-être pas applicable et nécessitera des modifications pour répondre aux besoins du personnel enseignant décentralisé.

Tensorial dynamic time warping with articulation index representation for efficient audio-template learning.

Audio classification techniques often depend on the availability of a large labeled training dataset for successful performance. However, in many application domains of audio classification (e.g., wildlife monitoring), obtaining labeled data is still a costly and laborious process. Motivated by this observation, a technique is proposed to efficiently learn a clean template from a few labeled, but likely corrupted (by noise and interferences), data samples. This learning can be done efficiently via tensorial dynamic time warping on the articulation index-based time-frequency representations of audio data. The learned template can then be used in audio classification following the standard template-based approach. Experimental results show that the proposed approach outperforms both (1) the recurrent neural network approach and (2) the state-of-the-art in the template-based approach on a wildlife detection application with few training samples.

Increased Susceptibility for Atrial and Ventricular Cardiac Arrhythmias in Mice Treated With a Single High Dose of Ibrutinib.

Atrial fibrillation is a side effect of ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase used for treatment of B-cell lymphoproliferative disorders. We determined if single (2 or 10 mg/kg), or chronic (14 days) oral ibrutinib followed by 24-hour washout conferred susceptibility to electrically induced arrhythmias in 1-month-old male C57BL/6 mice. A single higher dose of ibrutinib increased arrhythmia inducibility. There was no inducibility difference after chronic dosing with washout. This suggests that high serum drug levels might be responsible for the proarrhythmic effect of ibrutinib and that an altered dosing strategy might mitigate the side effects.

Atrial arrhythmias and autonomic dysfunction in rats exposed to chronic intermittent hypoxia.

Obstructive sleep apnea, which involves chronic intermittent hypoxia (CIH), is a major risk factor for developing atrial fibrillation (AF). Whether or not CIH alone alters cardiac mechanisms to support AF is unknown. This study investigated the effects of CIH on atrial electrophysiology and arrhythmia vulnerability and evaluated the role of autonomics in CIH promotion of AF. Adult male Sprague-Dawley rats were exposed to 8 h/day of CIH or normoxia for 7 days. After exposure, rats were anesthetized for intracardiac electrophysiological experiments. Atrial effective refractory periods (AERPs) and AF inducibility were determined using programmed electrical stimulation and burst pacing in the absence and presence of autonomic receptor agonists and antagonists. Western blot analysis measured atrial protein expression of muscarinic M2, M3, and ß1-adrenergic receptors. Compared with normoxia-exposed control rats, CIH-exposed rats had enhanced AF vulnerability using both programmed electrical stimulation and burst pacing, accompanied by greater AERP responses to carbachol and propranolol, lesser responses to isoproterenol, and higher atrial M2 receptor protein levels. Enhanced atrial vulnerability was accentuated by carbachol and abolished by atropine, indicating that the AF-promoting effects of CIH depended principally on parasympathetic activation. Enhancement of atrial vulnerability and AERP shortening with cholinergic agonists in CIH-exposed rats is consistent with sensitivity to parasympathetic activation. Higher responses to adrenergic receptor blockade in CIH-exposed rats is consistent with sympathetic potentiation. These findings implicate CIH as an important mediator of enhanced AF susceptibility in obstructive sleep apnea and provide novel insights into the underlying mechanisms. NEW & NOTEWORTHY Our study demonstrates, for the first time, that chronic intermittent hypoxia alone enhances vulnerability to atrial arrhythmia induction, which depends principally on parasympathetic activation. Enhanced atrial vulnerability was accompanied by heightened electrophysiological responses of the atrial myocardium to carbachol and isoproterenol, dampened responses to propranolol, and increased atrial M2 receptor protein levels.

Large-region acoustic source mapping using a movable array and sparse covariance fitting.

Large-region acoustic source mapping is important for city-scale noise monitoring. Approaches using a single-position measurement scheme to scan large regions using small arrays cannot provide clean acoustic source maps, while deploying large arrays spanning the entire region of interest is prohibitively expensive. A multiple-position measurement scheme is applied to scan large regions at multiple spatial positions using a movable array of small size. Based on the multiple-position measurement scheme, a sparse-constrained multiple-position vectorized covariance matrix fitting approach is presented. In the proposed approach, the overall sample covariance matrix of the incoherent virtual array is first estimated using the multiple-position array data and then vectorized using the Khatri-Rao (KR) product. A linear model is then constructed for fitting the vectorized covariance matrix and a sparse-constrained reconstruction algorithm is proposed for recovering source powers from the model. The user parameter settings are discussed. The proposed approach is tested on a 30 m × 40 m region and a 60 m × 40 m region using simulated and measured data. Much cleaner acoustic source maps and lower sound pressure level errors are obtained compared to the beamforming approaches and the previous sparse approach [Zhao, Tuna, Nguyen, and Jones, Proc. IEEE Intl. Conf. on Acoustics, Speech and Signal Processing (ICASSP) (2016)].

Drive-by large-region acoustic noise-source mapping via sparse beamforming tomography.

Environmental noise is a risk factor for human physical and mental health, demanding an efficient large-scale noise-monitoring scheme. The current technology, however, involves extensive sound pressure level (SPL) measurements at a dense grid of locations, making it impractical on a city-wide scale. This paper presents an alternative approach using a microphone array mounted on a moving vehicle to generate two-dimensional acoustic tomographic maps that yield the locations and SPLs of the noise-sources sparsely distributed in the neighborhood traveled by the vehicle. The far-field frequency-domain delay-and-sum beamforming output power values computed at multiple locations as the vehicle drives by are used as tomographic measurements. The proposed method is tested with acoustic data collected by driving an electric vehicle with a rooftop-mounted microphone array along a straight road next to a large open field, on which various pre-recorded noise-sources were produced by a loudspeaker at different locations. The accuracy of the tomographic imaging results demonstrates the promise of this approach for rapid, low-cost environmental noise-monitoring.

Representation of Stimulus Speed and Direction in Vibrissal-Sensitive Regions of the Trigeminal Nuclei: A Comparison of Single Unit and Population Responses.

The rat vibrissal (whisker) system is one of the oldest and most important models for the study of active tactile sensing and sensorimotor integration. It is well established that primary sensory neurons in the trigeminal ganglion respond to deflections of one and only one whisker, and that these neurons are strongly tuned for both the speed and direction of individual whisker deflections. During active whisking behavior, however, multiple whiskers will be deflected simultaneously. Very little is known about how neurons at central levels of the trigeminal pathway integrate direction and speed information across multiple whiskers. In the present work, we investigated speed and direction coding in the trigeminal brainstem nuclei, the first stage of neural processing that exhibits multi-whisker receptive fields. Specifically, we recorded both single-unit spikes and local field potentials from fifteen sites in spinal trigeminal nucleus interpolaris and oralis while systematically varying the speed and direction of coherent whisker deflections delivered across the whisker array. For 12/15 neurons, spike rate was higher when the whisker array was stimulated from caudal to rostral rather than rostral to caudal. In addition, 10/15 neurons exhibited higher firing rates for slower stimulus speeds. Interestingly, using a simple decoding strategy for the local field potentials and spike trains, classification of speed and direction was higher for field potentials than for single unit spike trains, suggesting that the field potential is a robust reflection of population activity. Taken together, these results point to the idea that population responses in these brainstem regions in the awake animal will be strongest during behaviors that stimulate a population of whiskers with a directionally coherent motion.

Effect of intermittent hypoxia on arcuate nucleus in the leptin-deficient rat.

Intermittent hypoxia (IH) is a major pathophysiological consequence of obstructive sleep apnea. Recently, it has been shown that IH results in changes in body energy balance, leptin secretion and concomitant alterations in arcuate nucleus (ARC). In this study, the role of leptin on these changes was investigated in leptin-deficient rats exposed to IH or normoxic control conditions. Body weights, consumatory and locomotor behaviours, and protein signaling in ARC were assessed immediately after IH exposure. Compared to normoxia, IH altered body weight, food intake, locomotor pattern, and the plasma concentration of leptin and angiotensin II in the wild-type rat. However, these changes were not observed in the leptin-deficient rat. Within ARC of wild-type animals, IH increased phosphorylated signal transducer and activator of transcription 3 and pro-opiomelanocortin protein expression, but not in the leptin-deficient rat. The long-form leptin receptor protein expression was not altered following IH in either rat strain. These data suggest that leptin is involved in mediating the alterations to body energy balance and ARC activity following IH.

A minimum-error, energy-constrained neural code is an instantaneous-rate code.

Sensory neurons code information about stimuli in their sequence of action potentials (spikes). Intuitively, the spikes should represent stimuli with high fidelity. However, generating and propagating spikes is a metabolically expensive process. It is therefore likely that neural codes have been selected to balance energy expenditure against encoding error. Our recently proposed optimal, energy-constrained neural coder (Jones et al. Frontiers in Computational Neuroscience, 9, 61 2015) postulates that neurons time spikes to minimize the trade-off between stimulus reconstruction error and expended energy by adjusting the spike threshold using a simple dynamic threshold. Here, we show that this proposed coding scheme is related to existing coding schemes, such as rate and temporal codes. We derive an instantaneous rate coder and show that the spike-rate depends on the signal and its derivative. In the limit of high spike rates the spike train maximizes fidelity given an energy constraint (average spike-rate), and the predicted interspike intervals are identical to those generated by our existing optimal coding neuron. The instantaneous rate coder is shown to closely match the spike-rates recorded from P-type primary afferents in weakly electric fish. In particular, the coder is a predictor of the peristimulus time histogram (PSTH). When tested against in vitro cortical pyramidal neuron recordings, the instantaneous spike-rate approximates DC step inputs, matching both the average spike-rate and the time-to-first-spike (a simple temporal code). Overall, the instantaneous rate coder relates optimal, energy-constrained encoding to the concepts of rate-coding and temporal-coding, suggesting a possible unifying principle of neural encoding of sensory signals.