Mismatch Negativity in Rat Auditory Cortex Represents the Empirical Salience of Sounds

Mismatch negativity (MMN) is an N-methyl-D-aspartic acid-mediated component and thus has been widely considered a major candidate biomarker of schizophrenia. However, at present, no direct evidence has linked the MMN response and aberrant salience processing reported in schizophrenia patients, i.e., whether MMN represents empirical salience of the deviant stimulus. To test the eligibility of the MMN response as a biomarker of schizophrenia, we hypothesized and verified that the MMN in the rat auditory cortex encodes empirical salience, which depends on both empirical rarity of sound and association of sound with salient events through classical conditioning. We exposed rats to sound or appetitive or aversive classical conditioning and extinction training of aversive conditioning, then recorded MMN from the auditory cortex. We focused on the frequency-dependent asymmetry of the MMN amplitude; increment frequency changes elicit asymmetrically larger MMN amplitudes than do decremental frequency changes. We found that sound exposure reversed this asymmetry in rats, indicating that MMN encodes the empirical rarity of deviant sounds. The MMN amplitude was larger in the appetitive or aversive classical conditioning groups, and smaller after extinction training following aversive conditioning. These results indicate that the MMN response reflects the empirical salience of sound. The present work first linked MMN with empirical salience processing and expands the possibilities of MMN as a strong clinical biomarker of schizophrenia

聴皮質における音の質感と情動情報の表現

学位の種別:課程博士University of Tokyo(東京大学

Wavelet Analysis for Wind Fields Estimation

Wind field analysis from synthetic aperture radar images allows the estimation of wind direction and speed based on image descriptors. In this paper, we propose a framework to automate wind direction retrieval based on wavelet decomposition associated with spectral processing. We extend existing undecimated wavelet transform approaches, by including à trous with B3 spline scaling function, in addition to other wavelet bases as Gabor and Mexican-hat. The purpose is to extract more reliable directional information, when wind speed values range from 5 to 10 ms−1. Using C-band empirical models, associated with the estimated directional information, we calculate local wind speed values and compare our results with QuikSCAT scatterometer data. The proposed approach has potential application in the evaluation of oil spills and wind farms

Influence of the meridional shifts of the Kuroshio and the Oyashio Extensions on the atmospheric circulation

Author Posting. © American Meteorological Society, 2011. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 24 (2011): 762-777, doi:10.1175/2010JCLI3731.1.The meridional shifts of the Oyashio Extension (OE) and of the Kuroshio Extension (KE), as derived from high-resolution monthly sea surface temperature (SST) anomalies in 1982–2008 and historical temperature profiles in 1979–2007, respectively, are shown based on lagged regression analysis to significantly influence the large-scale atmospheric circulation. The signals are independent from the ENSO teleconnections, which were removed by seasonally varying, asymmetric regression onto the first three principal components of the tropical Pacific SST anomalies. The response to the meridional shifts of the OE front is equivalent barotropic and broadly resembles the North Pacific Oscillation/western Pacific pattern in a positive phase for a northward frontal displacement. The response may reach 35 m at 250 hPa for a typical OE shift, a strong sensitivity since the associated SST anomaly is 0.5 K. However, the amplitude, but not the pattern or statistical significance, strongly depends on the lag and an assumed 2-month atmospheric response time. The response is stronger during fall and winter and when the front is displaced southward. The response to the northward KE shifts primarily consists of a high centered in the northwestern North Pacific and hemispheric teleconnections. The response is also equivalent barotropic, except near Kamchatka, where it tilts slightly westward with height. The typical amplitude is half as large as that associated with OE shifts.This work was supported in part by the L’Institut universitaire de France (CF), the WHOI Heyman fellowship, and the NASAGrant withAwardNNX09AF35G(Y.-O. K), and grants through NOAA’s Climate Variability and Predictability Program (MAA)

A cell-based high-throughput screening method to directly examine transthyretin amyloid fibril formation at neutral pH

Transthyretin (TTR) is a major amyloidogenic protein associated with hereditary (ATTRm) and nonhereditary (ATTRwt) intractable systemic transthyretin amyloidosis. The pathological mechanisms of ATTR-associated amyloid fibril formation are incompletely understood, and there is a need for identifying compounds that target ATTR. C-terminal TTR fragments are often present in amyloid-laden tissues of most patients with ATTR amyloidosis, and on the basis of in vitro studies, these fragments have been proposed to play important roles in amyloid formation. Here, we found that experimentally-formed aggregates of full-length TTR are cleaved into C-terminal fragments, which were also identified in patients' amyloid-laden tissues and in SH-SY5Y neuronal and U87MG glial cells. We observed that a 5-kDa C-terminal fragment of TTR, TTR81–127, is highly amyloidogenic in vitro, even at neutral pH. This fragment formed amyloid deposits and induced apoptosis and inflammatory gene expression also in cultured cells. Using the highly amyloidogenic TTR81–127 fragment, we developed a cell-based high-throughput screening method to discover compounds that disrupt TTR amyloid fibrils. Screening a library of 1280 off-patent drugs, we identified two candidate repositioning drugs, pyrvinium pamoate and apomorphine hydrochloride. Both drugs disrupted patient-derived TTR amyloid fibrils ex vivo, and pyrvinium pamoate also stabilized the tetrameric structure of TTR ex vivo in patient plasma. We conclude that our TTR81–127–based screening method is very useful for discovering therapeutic drugs that directly disrupt amyloid fibrils. We propose that repositioning pyrvinium pamoate and apomorphine hydrochloride as TTR amyloid-disrupting agents may enable evaluation of their clinical utility for managing ATTR amyloidosis

Characteristic patterns of QuikScat-based wind stress and turbulent heat flux in the tropical Indian Ocean

Using QuikScat-based vector wind data for 1999–2003, surface wind stress and turbulent heat (Q) have been mapped for the tropical Indian Ocean (IO) to understand their seasonal variability. During July wind stress is enhanced by ∼ 70% in the Arabian Sea compared to that during January. The Arabian Sea experiences a large Q loss (150–200 W/m2) during the summer and winter monsoons, which is nearly 1.3 times of that in the Bay of Bengal. The southeasterlies are strengthened during the southern hemisphere winter. Empirical Orthogonal Function analysis captures different phases of monsoon-induced variability in wind stress and Q, ranging from seasonal to high-frequency perturbations. Coherency between time coefficients of EOF-1 for wind stress and Q suggests that former leads the latter with a temporal lag of 20–40 days for period > 322 days. At high frequencies (< 21 days) Q leads wind stress with a temporal lag of 2 days. Possible explanation for wind stress leading Q over an annual time scale is offered based on the marine atmospheric boundary layer physics and pre-conditioned ocean surface, while on shorter time scales (21 days) ocean thermodynamics through mixed layer processes cause Q to lead wind stress

Preference test of sound among multiple alternatives in rats.

Conditioned place preference (CPP) tests in rodents have been well established to measure preference induced by secondary reinforcing properties, but conventional assays are not sensitive enough to measure innate, weak preference, or the primary reinforcing property of a conditioned stimulus. We designed a novel CPP assay with better sensitivity and efficiency in quantifying and ranking preference of particular sounds among multiple alternatives. Each test tone was presented according to the location of free-moving rats in the arena, where assignment of location to each tone changed in every 20-s session. We demonstrated that our assay was able to rank tone preference among 4 alternatives within 12.5 min (125 s (habituation) + 25 s/sessions × 25 sessions). In order to measure and rank sound preference, we attempted to use sojourn times with each test sound ([Formula: see text]), and a preference index (PI) based on transition matrices of initial and end sounds in every session. Both [Formula: see text] and PI revealed similar trends of innate preference in which rats preferred test conditions in the following order: silence, 40-, 20-, then 10-kHz tones. Further, rats exhibited a change in preference after an classical conditioning of the 20-kHz tone with a rewarding microstimulation of the dopaminergic system. We also demonstrated that PI was a more robust and sensitive indicator than [Formula: see text] when the locomotion activity level of rats became low due to habituation to the assay repeated over sessions. Thus, our assay offers a novel method of evaluating auditory preference that is superior to conventional CPP assays, offering promising prospects in the field of sensory neuroscience

Cortical mapping of mismatch negativity with deviance detection property in rat.

Mismatch Negativity (MMN) is an N-methyl-d-aspartic acid (NMDA)-mediated, negative deflection in human auditory evoked potentials in response to a cognitively discriminable change. MMN-like responses have been extensively investigated in animal models, but the existence of MMN equivalent is still controversial. In this study, we aimed to investigate how closely the putative MMN (MMNp) in rats exhibited the comparable properties of human MMN. We used a surface microelectrode array with a grid of 10 × 7 recording sites within an area of 4.5 × 3.0 mm to densely map evoked potentials in the auditory cortex of anesthetized rats under the oddball paradigm. Firstly, like human MMN, deviant stimuli elicited negative deflections in auditory evoked potentials following the positive middle-latency response, termed P1. Secondly, MMNp exhibited deviance-detecting property, which could not be explained by simple stimulus specific adaptation (SSA). Thirdly, this MMNp occurred focally in the auditory cortex, including both the core and belt regions, while P1 activation focus was obtained in the core region, indicating that both P1 and MMNp are generated in the auditory cortex, yet the sources of these signals do not completely overlap. Fourthly, MMNp significantly decreased after the application of AP5 (D-(-)-2-amino-5-phosphonopentanoic acid), an antagonist at NMDA receptors. In stark contrast, AP5 affected neither P1 amplitude nor SSA of P1. These results provide compelling evidence that the MMNp we have examined in rats is functionally comparable to human MMN. The present work will stimulate translational research into MMN, which may help bridge the gap between electroencephalography (EEG)/magnetoencephalography (MEG) studies in humans and electrophysiological studies in animals

The PALSAR Polarimetric Mode for Sea Oil Slick Observation

A study on sea oil slick observation by means of L-band polarimetric synthetic aperture radar (SAR) data is accomplished. It is based on different sea surface scattering mechanism expected with and without surface slicks. Polarimetric measurements are processed by means of a simple and very effective filtering technique which is electromagnetically based on the Mueller scattering matrix. Moreover, some polarimetric features, evaluated on both slick-free and slick-covered sea surfaces, are analyzed for confirming the filter output. Experiments are accomplished on the polarimetric SAR data acquired by the Phased Array-type L-band Synthetic Aperture Radar (PALSAR) sensor, mounted on board of the Advanced Land Observing Satellite (ALOS), and are relevant to oil slick, due to a tank accident, and look-alikes. Results demonstrate for the first time that L-band polarimetric SAR measurements are useful for oil slick observation purposes and witness the capability of the ALOS PALSAR data for such application