Intracellular Loop in the Brain Isoforms of Anoctamin 2 Channels Regulates Calcium-dependent Activation.

Anoctamin 2 (ANO2 or TMEM16B), a calcium-activated chloride channel (CaCC), performs diverse roles in neurons throughout the central nervous system. In hippocampal neurons, ANO2 narrows action potential width and reduces postsynaptic depolarization with high sensitivity to Ca2+ at relatively fast kinetics. In other brain regions, including the thalamus, ANO2 mediates activity-dependent spike frequency adaptations with low sensitivity to Ca2+ at relatively slow kinetics. How this same channel can respond to a wide range of Ca2+ levels remains unclear. We hypothesized that splice variants of ANO2 may contribute to its distinct Ca2+ sensitivity, and thus its diverse neuronal functions. We identified two ANO2 isoforms expressed in mouse brains and examined their electrophysiological properties: isoform 1 (encoded by splice variants with exons 1a, 2, 4, and 14) was expressed in the hippocampus, while isoform 2 (encoded by splice variants with exons 1a, 2, and 4) was broadly expressed throughout the brain, including in the cortex and thalamus, and had a slower calcium-dependent activation current than isoform 1. Computational modeling revealed that the secondary structure of the first intracellular loop of isoform 1 forms an entrance cavity to the calcium-binding site from the cytosol that is relatively larger than that in isoform 2. This difference provides structural evidence that isoform 2 is involved in accommodating spike frequency, while isoform 1 is involved in shaping the duration of an action potential and decreasing postsynaptic depolarization. Our study highlights the roles and molecular mechanisms of specific ANO2 splice variants in modulating neuronal functions.

Mouse fMRI under ketamine and xylazine anesthesia: Robust contralateral somatosensory cortex activation in response to forepaw stimulation.

Mouse fMRI is critically useful to investigate functions of mouse models. Until now, the somatosensory-evoked responses in anesthetized mice are often widespread and inconsistent across reports. Here, we adopted a ketamine and xylazine mixture for mouse fMRI, which is relatively new anesthetics in fMRI experiments. Forepaw stimulation frequency was optimized using cerebral blood volume (CBV)-weighted optical imaging (n = 11) and blood-oxygenation-level dependent (BOLD) fMRI with a gradient-echo time of 16 ms at 9.4 T, and 4 Hz stimulation with 0.5 ms and 0.5 mA pulses induced the highest hemodynamic response. For 20-s 4-Hz unilateral forepaw stimulation, localized BOLD activity was consistently found in the contralateral primary forelimb somatosensory cortex (S1FL), while no significant change was observed in the ipsilateral S1FL. The mean magnitude was 1.44 ±â€¯0.20% SEM (n = 9) in the contralateral S1FL and 0.69 ±â€¯0.10% in the contralateral thalamus. The variability of evoked fMRI responses across sessions was investigated by comparing with resting state fMRI (rsfMRI) functional connectivity (FC). Evoked responses in S1FL were correlated positively with rsfMRI FC between bilateral S1FL (r = 0.63 to 0.69) and negatively with FC between S1FL and the anterior cingulate cortex (r = -0.50 to -0.57), suggesting that rsfMRI FC is a good index of the evoked fMRI response and anesthetized animal condition. Finally, three weekly fMRI scans were performed in 5 mice, and localized activity was reproducibly observed in S1FL, with a success rate of 70-95%. In summary, our developed fMRI protocol can be used for mapping functions of mouse models.

Counter-Based Broadcast Scheme Considering Reachability, Network Density, and Energy Efficiency for Wireless Sensor Networks.

A wireless sensor network (WSN) is emerging as an innovative method for gathering information that will significantly improve the reliability and efficiency of infrastructure systems. Broadcast is a common method to disseminate information in WSNs. A variety of counter-based broadcast schemes have been proposed to mitigate the broadcast-storm problems, using the count threshold value and a random access delay. However, because of the limited propagation of the broadcast-message, there exists a trade-off in a sense that redundant retransmissions of the broadcast-message become low and energy efficiency of a node is enhanced, but reachability become low. Therefore, it is necessary to study an efficient counter-based broadcast scheme that can dynamically adjust the random access delay and count threshold value to ensure high reachability, low redundant of broadcast-messages, and low energy consumption of nodes. Thus, in this paper, we first measure the additional coverage provided by a node that receives the same broadcast-message from two neighbor nodes, in order to achieve high reachability with low redundant retransmissions of broadcast-messages. Second, we propose a new counter-based broadcast scheme considering the size of the additional coverage area, distance between the node and the broadcasting node, remaining battery of the node, and variations of the node density. Finally, we evaluate performance of the proposed scheme compared with the existing counter-based broadcast schemes. Simulation results show that the proposed scheme outperforms the existing schemes in terms of saved rebroadcasts, reachability, and total energy consumption.

Bio-Inspired Distributed Transmission Power Control Considering QoS Fairness in Wireless Body Area Sensor Networks.

Recently, the development of wireless body area sensor network (WBASN) has accelerated due to the rapid development of wireless technology. In the WBASN environment, many WBASNs coexist where communication ranges overlap with each other, resulting in the possibility of interference. Although nodes in a WBASN typically operate at a low power level, to avoid adversely affecting the human body, high transmission rates may be required to support some applications. In addition to this, since many varieties of applications exist in the WBASN environment, each prospective user may have different quality of service (QoS) requirements. Hence, the following issues should be considered in the WBASN environment: (1) interference between adjacent WBASNs, which influences the performance of a specific system, and (2) the degree of satisfaction on the QoS of each user, i.e., the required QoS such as user throughput should be considered to ensure that all users in the network are provided with a fair QoS satisfaction. Thus, in this paper, we propose a transmission power adjustment algorithm that addresses interference problems and guarantees QoS fairness between users. First, we use a new utility function to measure the degree of the satisfaction on the QoS for each user. Then, the transmission power of each sensor node is calculated using the Cucker-Smale model, and the QoS satisfaction of each user is synchronized dispersively. The results of simulations show that the proposed algorithm performs better than existing algorithms, with respect to QoS fairness and energy efficiency.

A novel pre-processing technique for improving image quality in digital breast tomosynthesis.

PURPOSE: Nonlinear pre-reconstruction processing of the projection data in computed tomography (CT) where accurate recovery of the CT numbers is important for diagnosis is usually discouraged, for such a processing would violate the physics of image formation in CT. However, one can devise a pre-processing step to enhance detectability of lesions in digital breast tomosynthesis (DBT) where accurate recovery of the CT numbers is fundamentally impossible due to the incompleteness of the scanned data. Since the detection of lesions such as micro-calcifications and mass in breasts is the purpose of using DBT, it is justified that a technique producing higher detectability of lesions is a virtue. METHODS: A histogram modification technique was developed in the projection data domain. Histogram of raw projection data was first divided into two parts: One for the breast projection data and the other for background. Background pixel values were set to a single value that represents the boundary between breast and background. After that, both histogram parts were shifted by an appropriate amount of offset and the histogram-modified projection data were log-transformed. Filtered-backprojection (FBP) algorithm was used for image reconstruction of DBT. To evaluate performance of the proposed method, we computed the detectability index for the reconstructed images from clinically acquired data. RESULTS: Typical breast border enhancement artifacts were greatly suppressed and the detectability of calcifications and masses was increased by use of the proposed method. Compared to a global threshold-based post-reconstruction processing technique, the proposed method produced images of higher contrast without invoking additional image artifacts. CONCLUSIONS: In this work, we report a novel pre-processing technique that improves detectability of lesions in DBT and has potential advantages over the global threshold-based post-reconstruction processing technique. The proposed method not only increased the lesion detectability but also reduced typical image artifacts pronounced in conventional FBP-based DBT.

The thalamic mGluR1-PLCß4 pathway is critical in sleep architecture.

The transition from wakefulness to a nonrapid eye movement (NREM) sleep state at the onset of sleep involves a transition from low-voltage, high-frequency irregular electroencephalography (EEG) waveforms to large-amplitude, low-frequency EEG waveforms accompanying synchronized oscillatory activity in the thalamocortical circuit. The thalamocortical circuit consists of reciprocal connections between the thalamus and cortex. The cortex sends strong excitatory feedback to the thalamus, however the function of which is unclear. In this study, we investigated the role of the thalamic metabotropic glutamate receptor 1 (mGluR1)-phospholipase C ß4 (PLCß4) pathway in sleep control in PLCß4-deficient (PLCß4-/-) mice. The thalamic mGluR1-PLCß4 pathway contains synapses that receive corticothalamic inputs. In PLCß4-/- mice, the transition from wakefulness to the NREM sleep state was stimulated, and the NREM sleep state was stabilized, which resulted in increased NREM sleep. The power density of delta (δ) waves increased in parallel with the increased NREM sleep. These sleep phenotypes in PLCß4-/- mice were consistent in TC-restricted PLCß4 knockdown mice. Moreover, in vitro intrathalamic oscillations were greatly enhanced in the PLCß4-/- slices. The results of our study showed that thalamic mGluR1-PLCß4 pathway was critical in controlling sleep architecture.

Dynamic Power-Saving Method for Wi-Fi Direct Based IoT Networks Considering Variable-Bit-Rate Video Traffic.

With the arrival of the era of Internet of Things (IoT), Wi-Fi Direct is becoming an emerging wireless technology that allows one to communicate through a direct connection between the mobile devices anytime, anywhere. In Wi-Fi Direct-based IoT networks, all devices are categorized by group of owner (GO) and client. Since portability is emphasized in Wi-Fi Direct devices, it is essential to control the energy consumption of a device very efficiently. In order to avoid unnecessary power consumed by GO, Wi-Fi Direct standard defines two power-saving methods: Opportunistic and Notice of Absence (NoA) power-saving methods. In this paper, we suggest an algorithm to enhance the energy efficiency of Wi-Fi Direct power-saving, considering the characteristics of multimedia video traffic. Proposed algorithm utilizes the statistical distribution for the size of video frames and adjusts the lengths of awake intervals in a beacon interval dynamically. In addition, considering the inter-dependency among video frames, the proposed algorithm ensures that a video frame having high priority is transmitted with higher probability than other frames having low priority. Simulation results show that the proposed method outperforms the traditional NoA method in terms of average delay and energy efficiency.

Analysis of Aggregation Delay for Multisource Sensor Data with On-Off Traffic Pattern in Wireless Body Area Networks.

Data aggregation plays an important role to improve the transmission efficiency in wireless body area networks (WBANs); however, it inherently induces additional aggregation delay. Therefore, the effect of packet aggregation on WBAN applications, which are vulnerable to delay, must be analyzed rigorously. In this paper, we analyze the packet aggregation delay for multisource sensor data with an on-off traffic pattern in WBANs. Considering two operational parameters of the aggregation threshold and aggregation timer, we calculate the probability that a packet aggregation occurs during a unit time and then derive the average aggregation delay in closed-form. The analysis results show that the aggregation delay increases as the aggregation timer or aggregation threshold increases, but is bounded below a certain level according to the number of active sensors and their on-off traffic attribute. This implies that the data aggregation technique can maximize the transmission efficiency while satisfying a given delay requirement in the WBAN system.

An Image-Based Reduction of Metal Artifacts in Computed Tomography.

OBJECTIVE: Various strategies have been developed in the past to reduce the excessive effects of metal artifacts in computed tomography images. From straightforward sinogram inpainting-based methods to computationally expensive iterative methods, all have been successful in improving the image quality up to a certain degree. We propose a novel image-based metal artifact subtraction method that achieves a superior image quality and at the same time provides a quantitatively more accurate image. METHODS: Our proposed method consists of prior image-based sinogram inpainting, metal sinogram extraction, and metal artifact image subtraction. Reconstructing the metal images from the extracted metal-contaminated portions in the sinogram yields a streaky image that eventually can be subtracted from the uncorrected image. The prior image is reconstructed from the sinogram that is free from the metal-contaminated portions by use of a total variation (TV) minimization algorithm, and the reconstructed prior image is fed into the forward projector so that the missing portions in the sinogram can be recovered. Image quality of the metal artifact-reduced images on selected areas was assessed by the structure similarity index for the simulated data and SD for the real dental data. RESULTS: Simulation phantom studies showed higher structure similarity index values for the proposed metal artifact reduction (MAR) images than the standard MAR images. Thus, more artifact suppression was observed in proposed MAR images. In real dental phantom data study, lower SD values were calculated from the proposed MAR images. The findings in real human arm study were also consistent with the results in all phantom studies. Thus, compared with standard MAR images, lesser artifact intensity was exhibited by the proposed MAR images. CONCLUSIONS: From the quantitative calculations, our proposed method has shown to be effective and superior to the conventional approach in both simulation and real dental phantom cases.

Design and performance evaluation of a distributed OFDMA-based MAC protocol for MANETs.

In this paper, we propose a distributed MAC protocol for OFDMA-based wireless mobile ad hoc multihop networks, in which the resource reservation and data transmission procedures are operated in a distributed manner. A frame format is designed considering the characteristics of OFDMA that each node can transmit or receive data to or from multiple nodes simultaneously. Under this frame structure, we propose a distributed resource management method including network state estimation and resource reservation processes. We categorize five types of logical errors according to their root causes and show that two of the logical errors are inevitable while three of them are avoided under the proposed distributed MAC protocol. In addition, we provide a systematic method to determine the advertisement period of each node by presenting a clear relation between the accuracy of estimated network states and the signaling overhead. We evaluate the performance of the proposed protocol in respect of the reservation success rate and the success rate of data transmission. Since our method focuses on avoiding logical errors, it could be easily placed on top of the other resource allocation methods focusing on the physical layer issues of the resource management problem and interworked with them.

Sleep spindles are generated in the absence of T-type calcium channel-mediated low-threshold burst firing of thalamocortical neurons.

T-type Ca(2+) channels in thalamocortical (TC) neurons have long been considered to play a critical role in the genesis of sleep spindles, one of several TC oscillations. A classical model for TC oscillations states that reciprocal interaction between synaptically connected GABAergic thalamic reticular nucleus (TRN) neurons and glutamatergic TC neurons generates oscillations through T-type channel-mediated low-threshold burst firings of neurons in the two nuclei. These oscillations are then transmitted from TC neurons to cortical neurons, contributing to the network of TC oscillations. Unexpectedly, however, we found that both WT and KO mice for CaV3.1, the gene for T-type Ca(2+) channels in TC neurons, exhibit typical waxing-and-waning sleep spindle waves at a similar occurrence and with similar amplitudes and episode durations during non-rapid eye movement sleep. Single-unit recording in parallel with electroencephalography in vivo confirmed a complete lack of burst firing in the mutant TC neurons. Of particular interest, the tonic spike frequency in TC neurons was significantly increased during spindle periods compared with nonspindle periods in both genotypes. In contrast, no significant change in burst firing frequency between spindle and nonspindle periods was noted in the WT mice. Furthermore, spindle-like oscillations were readily generated within intrathalamic circuits composed solely of TRN and TC neurons in vitro in both the KO mutant and WT mice. Our findings call into question the essential role of low-threshold burst firings in TC neurons and suggest that tonic firing is important for the generation and propagation of spindle oscillations in the TC circuit.

Deletion of phospholipase C beta4 in thalamocortical relay nucleus leads to absence seizures.

Absence seizures are characterized by cortical spike-wave discharges (SWDs) on electroencephalography, often accompanied by a shift in the firing pattern of thalamocortical (TC) neurons from tonic to burst firing driven by T-type Ca(2+) currents. We recently demonstrated that the phospholipase C beta4 (PLCbeta4) pathway tunes the firing mode of TC neurons via the simultaneous regulation of T- and L-type Ca(2+) currents, which prompted us to investigate the contribution of TC firing modes to absence seizures. PLCbeta4-deficient TC neurons were readily shifted to the oscillatory burst firing mode after a slight hyperpolarization of membrane potential. TC-limited knockdown as well as whole-animal knockout of PLCbeta4 induced spontaneous SWDs with simultaneous behavioral arrests and increased the susceptibility to drug-induced SWDs, indicating that the deletion of thalamic PLCbeta4 leads to the genesis of absence seizures. The SWDs were effectively suppressed by thalamic infusion of a T-type, but not an L-type, Ca(2+) channel blocker. These results reveal a primary role of TC neurons in the genesis of absence seizures and provide strong evidence that an alteration of the firing property of TC neurons is sufficient to generate absence seizures. Our study presents PLCbeta4-deficient mice as a potential animal model for absence seizures.

T-type Ca2+ channels as therapeutic targets in the nervous system.

Low-voltage-activated calcium channels, also known as T-type calcium channels, are widely expressed in various types of neurons. In contrast to high-voltage-activated calcium channels which can be activated by a strong depolarization of membrane potential, T-type channels can be activated by a weak depolarization near the resting membrane potential once deinactivated by hyperpolarization, and therefore can regulate the excitability and electroresponsiveness of neurons under physiological conditions near resting states. Recently, the molecular diversity and functional multiplicity of T-type channels have been demonstrated through molecular genetic studies coupled with physiological and behavioral analysis. Understanding the functional consequences of modulation of each subtype of these channels in vivo could point to the right direction for developing therapeutic tools for relevant diseases.

T-type calcium channels and thalamocortical rhythms in sleep: a perspective from studies of T-type calcium channel knockout mice.

Sleep is characterized by synchronized electrical activities of the thalamocortical network, which can be identified as the EEG oscillations during sleep. T-type calcium channels have been implicated in the occurrence of sleep waves, and burst firings in the thalamic neurons driven by these channels are known to be essential for modulation of sleep rhythms. Studies showed that alpha1(G) T-type calcium channel knockout mice had defects in sleep waves such as lack of delta oscillations (1-4 Hz) and alteration of sleep spindles (7-15 Hz), which are known to be modulated by T-currents in the thalamus. The mutation also affected the sleep-wake transition, thus resulting in decreased NREM sleep and increased sleep disturbance. These findings support the idea that alpha1(G) T-type calcium channels contribute to sleep waves as well as to behavioral state of sleep.

Genetic studies on the role of T-type Ca2+ channels in sleep and absence epilepsy.

Thalamocortical neurons in mammals fire action potentials in two different modes, burst or tonic, depending on the cellular state. The burst firing is driven by the low threshold Ca2+ spike that is generated by Ca2+ influx through T-type Ca2+ channels, and has long been implicated in the pathogenesis of absence epilepsy and the regulation of sleep rhythms. The recent availability of the knock-out mice for the alpha1G locus, encoding the predominant form of T-type channels in thalamocortical neurons, has provided an opportunity to examine those ideas at the level of organism. In this review we will describe recent results demonstrating the essential role of thalamic bursts in certain forms of absence seizures and in some of the sleep rhythms. Available information so far reveals the sensory gating role of thalamic bursts, and thus of alpha1G T-type channels. Understanding of the molecular targets involved in pathophysiological mechanisms will help develop drugs to control those pathological states.

Lack of delta waves and sleep disturbances during non-rapid eye movement sleep in mice lacking alpha1G-subunit of T-type calcium channels.

T-type calcium channels have been implicated as a pacemaker for brain rhythms during sleep but their contribution to behavioral states of sleep has been relatively uncertain. Here, we found that mice lacking alpha1(G) T-type Ca(2+) channels showed a loss of the thalamic delta (1-4 Hz) waves and a reduction of sleep spindles (7-14 Hz), whereas slow (<1 Hz) rhythms were relatively intact, when compared with the wild-type during urethane anesthesia and non-rapid eye movement (NREM) sleep. Analysis of sleep disturbances, as defined by the occurrence of brief awakening (BA) episodes during NREM sleep, revealed that mutant mice exhibited a higher incidence of BAs of >16 sec compared with the wild-type, whereas no difference was seen in BAs of <16 sec between the two genotypes. These results are consistent with the previous idea of the distinct nature of delta oscillations and sleep spindles from cortically generated slow waves. These results also suggest that the alpha1(G)-subunit of T-type calcium channels plays a critical role in the genesis of thalamocortical oscillations and contributes to the modulation of sleep states and the transition between NREM sleep and wake states.