Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice

社会性の発達を調節する新たな機構を発見. 京都大学プレスリリース. 2021-03-26.Neuroligin 3 (NLGN3) and neurexins (NRXNs) constitute a canonical transsynaptic cell-adhesion pair, which has been implicated in autism. In autism spectrum disorder (ASD) development of sociality can be impaired. However, the molecular mechanism underlying NLGN3-mediated social development is unclear. Here, we identify non-canonical interactions between NLGN3 and protein tyrosine phosphatase δ (PTPδ) splice variants, competing with NRXN binding. NLGN3-PTPδ complex structure revealed a splicing-dependent interaction mode and competition mechanism between PTPδ and NRXNs. Mice carrying a NLGN3 mutation that selectively impairs NLGN3-NRXN interaction show increased sociability, whereas mice where the NLGN3-PTPδ interaction is impaired exhibit impaired social behavior and enhanced motor learning, with imbalance in excitatory/inhibitory synaptic protein expressions, as reported in the Nlgn3 R451C autism model. At neuronal level, the autism-related Nlgn3 R451C mutation causes selective impairment in the non-canonical pathway. Our findings suggest that canonical and non-canonical NLGN3 pathways compete and regulate the development of sociality

Construction of convergent adaptive weighted essentially non-oscillatory schemes for Hamilton-Jacobi equations on triangular meshes

summary:We propose a method of constructing convergent high order schemes for Hamilton-Jacobi equations on triangular meshes, which is based on combining a high order scheme with a first order monotone scheme. According to this methodology, we construct adaptive schemes of weighted essentially non-oscillatory type on triangular meshes for nonconvex Hamilton-Jacobi equations in which the first order monotone approximations are occasionally applied near singular points of the solution (discontinuities of the derivative) instead of weighted essentially non-oscillatory approximations. Through detailed numerical experiments, the convergence and effectiveness of the proposed adaptive schemes are demonstrated

Development of a Warning System to Detect Urinary Incontinence from Outside of a Diaper using a Reusable Sensor

The number of elderly individuals in need of care is increasing with the growing elderly population in Japan, resulting in the increased production of disposable diapers. Several warning detectors for urinary incontinence have been developed to provide high-quality care, several of which have been marketed. Most of these detectors use disposable sensors. These sensors must be attached to a new diaper at the time of diaper changing. To reduce both the effort and the cost required to replace the sensor, we developed a warning system to detect urinary incontinence using a reusable sensor on the outside of a diaper. The newly developed system is essentially divided into a sensor unit and an alarm unit. The sensor unit consists of a pair of electrodes; a timer; a signal generator; bridge, rectifier, and smoother circuits; and a transmitter. The alarm unit consists of a receiver and LEDs. The alarm unit delivers a warning about incontinence to care staff via LED lighting. When 500 mL of tap water was absorbed into a diaper, on the outside of which the system was attached by its electrodes, the capacitance and conductance increased 2.5 times and 50 times, respectively, compared with those of a dry diaper. When 50 mL of saline was poured into a diaper that was attached to the crotch region of a torso mannequin to model incontinence, the incontinence warning functioned as intended. The impedance of the pad-type diaper, which was measured by an impedance analyzer, decreased from 270 kΩ to 86 kΩ. The electrodes remained dry after the saline was poured into the diaper. The novel warning system was evaluated in a special nursing home for the aged. Twelve elderly people participated in this trial. The system operated correctly in 49 of 65 trials

Involuntary Measurement System for Respiratory Waveform for Prevention of Accidental Drowning during Bathing

Death rate of accidental drowning in the bathtub was the highest among casualties occurring at home, according to the annual report of the Japanese Ministry of Health, Labour and Welfare in 2007. To prevent accidental drowning during bathing at home, we obtained respiratory waveforms from bioelectric impedance (BEI) measurement using non-contact electrodes. The BEI measurement is an involuntary measurement method, from which respiratory waveform during bathing can be extracted. In the present study, to find the most appropriate electrode configuration as well as the optimal measuring frequency, we calculated the frequency dependence of impedance amplitude by numerical technique based on a three-dimensional finite difference method for a composite system consisting of a human body submerged in bath water. The results of model calculation agreed with the experimental results. Next, to obtain respiratory waveforms with large amplitudes, we investigated the optimal frequency experimentally. The frequency of 1MHz was suitable for involuntary measurement of respiratory waveform during bathing

Orexin/Hypocretin and Organizing Principles for a Diversity of Wake-Promoting Neurons in the Brain.

An enigmatic feature of behavioural state control is the rich diversity of wake-promoting neural systems. This diversity has been rationalized as 'robustness via redundancy', wherein wakefulness control is not critically dependent on one type of neuron or molecule. Studies of the brain orexin/hypocretin system challenge this view by demonstrating that wakefulness control fails upon loss of this neurotransmitter system. Since orexin neurons signal arousal need, and excite other wake-promoting neurons, their actions illuminate nonredundant principles of arousal control. Here, we suggest such principles by reviewing the orexin system from a collective viewpoint of biology, physics and engineering. Orexin peptides excite other arousal-promoting neurons (noradrenaline, histamine, serotonin, acetylcholine neurons), either by activating mixed-cation conductances or by inhibiting potassium conductances. Ohm's law predicts that these opposite conductance changes will produce opposite effects on sensitivity of neuronal excitability to current inputs, thus enabling orexin to differentially control input-output gain of its target networks. Orexin neurons also produce other transmitters, including glutamate. When orexin cells fire, glutamate-mediated downstream excitation displays temporal decay, but orexin-mediated excitation escalates, as if orexin transmission enabled arousal controllers to compute a time integral of arousal need. Since the anatomical and functional architecture of the orexin system contains negative feedback loops (e.g. orexin ➔ histamine ➔ noradrenaline/serotonin-orexin), such computations may stabilize wakefulness via integral feedback, a basic engineering strategy for set point control in uncertain environments. Such dynamic behavioural control requires several distinct wake-promoting modules, which perform nonredundant transformations of arousal signals and are connected in feedback loops