Hearing ability of prairie voles (Microtus ochrogaster).

The hearing abilities of mammals are impacted by factors such as social cues, habitat, and physical characteristics. Despite being used commonly to study social behaviors, hearing of the monogamous prairie vole (Microtus ochrogaster) has never been characterized. In this study, anatomical features are measured and auditory brainstem responses (ABRs) are used to measure auditory capabilities of prairie voles, characterizing monaural and binaural hearing and hearing range. Sexually naive male and female voles were measured to characterize differences due to sex. It was found that prairie voles show a hearing range with greatest sensitivity between 8 and 32 kHz, binaural hearing across interaural time difference ranges appropriate for their head sizes. No differences are shown between the sexes in binaural hearing or hearing range (except at 1 kHz), however, female voles have increased amplitude of peripheral ABR waves I and II and longer latency of waves III and IV compared to males. The results confirm that prairie voles have a broad hearing range, binaural hearing consistent with rodents of similar size, and differences in amplitudes and thresholds of monaural physiological measures between the sexes. These data further highlight the necessity to understand sex-specific differences in neural processing that may underly variability in responses between sexes.

An unsupervised real-time spike sorting system based on optimized OSort.

Objective. The OSort algorithm, a pivotal unsupervised spike sorting method, has been implemented in dedicated hardware devices for real-time spike sorting. However, due to the inherent complexity of neural recording environments, OSort still grapples with numerous transient cluster occurrences during the practical sorting process. This leads to substantial memory usage, heavy computational load, and complex hardware architectures, especially in noisy recordings and multi-channel systems.Approach. This study introduces an optimized OSort algorithm (opt-OSort) which utilizes correlation coefficient (CC), instead of Euclidean distance as classification criterion. TheCCmethod not only bolsters the robustness of spike classification amidst the diverse and ever-changing conditions of physiological and recording noise environments, but also can finish the entire sorting procedure within a fixed number of cluster slots, thus preventing a large number of transient clusters. Moreover, the opt-OSort incorporates two configurable validation loops to efficiently reject cluster outliers and track recording variations caused by electrode drifting in real-time.Main results. The opt-OSort significantly reduces transient cluster occurrences by two orders of magnitude and decreases memory usage by 2.5-80 times in the number of pre-allocated transient clusters compared with other hardware implementations of OSort. The opt-OSort maintains an accuracy comparable to offline OSort and other commonly-used algorithms, with a sorting time of 0.68µs as measured by the hardware-implemented system in both simulated datasets and experimental data. The opt-OSort's ability to handle variations in neural activity caused by electrode drifting is also demonstrated.Significance. These results present a rapid, precise, and robust spike sorting solution suitable for integration into low-power, portable, closed-loop neural control systems and brain-computer interfaces.

Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice.

Auxilin (DNAJC6/PARK19), an endocytic co-chaperone, is essential for maintaining homeostasis in the readily releasable pool (RRP) by aiding clathrin-mediated uncoating of synaptic vesicles. Its loss-of-function mutations, observed in familial Parkinson's disease (PD), lead to basal ganglia motor deficits and cortical dysfunction. We discovered that auxilin-knockout (Aux-KO) mice exhibited impaired pre-synaptic plasticity in layer 4 to layer 2/3 pyramidal cell synapses in the primary visual cortex (V1), including reduced short-term facilitation and depression. Computational modeling revealed increased RRP refilling during short repetitive stimulation, which diminished during prolonged stimulation. Silicon probe recordings in V1 of Aux-KO mice demonstrated disrupted visual cortical circuit responses, including reduced orientation selectivity, compromised visual mismatch negativity, and shorter visual familiarity-evoked theta oscillations. Pupillometry analysis revealed an impaired optokinetic response. Auxilin-dependent pre-synaptic endocytosis dysfunction was associated with deficits in pre-synaptic plasticity, visual cortical functions, and eye movement prodromally or at the early stage of motor symptoms.

Modulating Individual Alpha Frequency through Short-Term Neurofeedback for Cognitive Enhancement in Healthy Young Adults.

Human alpha oscillation (7-13 Hz) has been extensively studied over the years for its connection with cognition. The individual alpha frequency (IAF), defined as the frequency that provides the highest power in the alpha band, shows a positive correlation with cognitive processes. The modulation of alpha activities has been accomplished through various approaches aimed at improving cognitive performance. However, very few studies focused on the direct modulation of IAF by shifting the peak frequency, and the understanding of IAF modulation remains highly limited. In this study, IAFs of healthy young adults were up-regulated through short-term neurofeedback training using haptic feedback. The results suggest that IAFs have good trainability and are up-regulated, also that IAFs are correlated with the enhanced cognitive performance in mental rotation and n-back tests compared to sham-neurofeedback control. This study demonstrates the feasibility of self-regulating IAF for cognition enhancement and provides potential therapeutic benefits for cognitive-impaired patients.

IL-22RA2 Is a SMAD7 Target Mediating the Alleviation of Dermatitis and Psoriatic Phenotypes in Mice.

Long-term management of inflammatory skin diseases is challenging because of side effects from repeated use of systemic treatments or topical corticosteroids. This study sought to identify the mechanisms and developmental therapeutics for these diseases using genetic models and pharmacological approaches. We found that mice overexpressing SMAD7 in keratinocytes but not mice overexpressing the N-terminal domain of SMAD7 (i.e., N-SMAD7) were resistant to imiquimod-induced T helper 1/17- and T helper 2-type inflammation. We generated a Tat-PYC-SMAD7 (truncated SMAD7 protein encompassing C-terminal SMAD7 and PY motif fused with cell-penetrating Tat peptide). Topically applied Tat-PYC-SMAD7 to inflamed skin entered cells upon contact and attenuated imiquimod-, 2,4-dinitrofluorobenzene-, and tape-stripping-induced inflammation. RNA-sequencing analyses of mouse skin exposed to these insults showed that in addition to inhibiting TGFß/NF-κB, SMAD7 blunted IL-22/signal transducer and activator of transcription 3 activation and associated pathogenesis, which is due to SMAD7 transcriptionally upregulating IL-22 antagonist IL-22RA2. Mechanistically, SMAD7 facilitated nuclear translocation and DNA binding of C/EBPß to IL22RA2 promoter for IL22RA2 transactivation. Consistent with the observations in mice mentioned earlier, transcript levels of IL22RA2 were increased in human atopic dermatitis and psoriasis lesions with clinical remission. Our study identified the anti-inflammation functional domain of SMAD7 and suggests the mechanism and feasibility for developing SMAD7-based biologics as a topical therapy for skin inflammatory disorders.

Current Best Practices for Analysis of Dendritic Spine Morphology and Number in Neurodevelopmental Disorder Research.

Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new techniques develop, it is not always clear when and how each may be used to answer specific scientific questions posed. Dendritic spines, which are often indicative of synapse formation and neural plasticity, have been implicated across many brain regions in neurodevelopmental disorders as a marker for neural changes reflecting neural dysfunction or alterations. In this Perspective we highlight several techniques for staining, imaging, and quantifying dendritic spines as well as provide a framework for avoiding potential issues related to pseudoreplication. This framework illustrates how others may apply the most rigorous approaches. We consider the cost-benefit analysis of the varied techniques, recognizing that the most sophisticated equipment may not always be necessary for answering some research questions. Together, we hope this piece will help researchers determine the best strategy toward using the ever-growing number of techniques available to determine neural changes underlying dendritic spine morphology in health and neurodevelopmental disorders.

A method for non-destructive microwave focusing for deep brain and tissue stimulation.

Non-invasive stimulation of biological tissue is highly desirable for several biomedical applications. Of specific interest are methods for tumor treatment, endometrial ablation, and neuro-modulation. In traditional neuro-modulation, single- and multi-coil transcranial stimulation techniques in low oscillation frequencies are utilized to non-invasively penetrate the skull and elicit action potentials in cortical neurons. Although these methods have been proven effective, tightly focusing these signals to localized regions is difficult. In recent years, microwave (MW) methods have seen an increase usage as a minimally invasive treatment modality for ablation and neuro-stimulation. Unlike low frequency signals, MW signals can be focused to localized sub-centimeter regions. In this work we demonstrate that a three-dimensional array of MW antennas can be used to tightly focus signals to a localized region in space within the human body with MW frequencies. Assuming an array of small MW loop antennas are placed around the body, the optimal amplitude and phase of each array element can be accurately determined to match an arbitrary desired field profile. The major innovation of the presented method is that the fields that penetrate the biological region are determined via computing numerical Green's functions (NGF) that are then used to drive an optimization algorithm. Using simplified models of regions in the human body, it is shown that the MW fields at 1 GHz can be focused to sub-centimeter sized "hot spots" at depths of several centimeters. The algorithm can be easily extended to more realistic models of the human body or for non-biological applications.

Predicting the Influence of Axon Myelination on Sound Localization Precision Using a Spiking Neural Network Model of Auditory Brainstem.

Spatial hearing allows animals to rapidly detect and localize auditory events in the surrounding environment. The auditory brainstem plays a central role in processing and extracting binaural spatial cues through microsecond-precise binaural integration, especially for detecting interaural time differences (ITDs) of low-frequency sounds at the medial superior olive (MSO). A series of mechanisms exist in the underlying neural circuits for preserving accurate action potential timing across multiple fibers, synapses and nuclei along this pathway. One of these is the myelination of afferent fibers that ensures reliable and temporally precise action potential propagation in the axon. There are several reports of fine-tuned myelination patterns in the MSO circuit, but how specifically myelination influences the precision of sound localization remains incompletely understood. Here we present a spiking neural network (SNN) model of the Mongolian gerbil auditory brainstem with myelinated axons to investigate whether different axon myelination thicknesses alter the sound localization process. Our model demonstrates that axon myelin thickness along the contralateral pathways can substantially modulate ITD detection. Furthermore, optimal ITD sensitivity is reached when the MSO receives contralateral inhibition via thicker myelinated axons compared to contralateral excitation, a result that is consistent with previously reported experimental observations. Our results suggest specific roles of axon myelination for extracting temporal dynamics in ITD decoding, especially in the pathway of the contralateral inhibition.

Axonal Conduction Delay Shapes the Precision of the Spatial Hearing in A Spiking Neural Network Model of Auditory Brainstem.

One method by which the mammalian sound localization pathway localizes sound sources is by analyzing the microsecond-level difference between the arrival times of a sound at the two ears. However, how the neural circuits in the auditory brainstem precisely integrate signals from the two ears, and what the underlying mechanisms are, remains to be understood. Recent studies have reported that variations of axon myelination in the auditory brainstem produces various axonal conduction velocities and sophisticated temporal dynamics, which have not been well characterized in most existing models of sound localization circuits. Here, we present a spiking neural network model of the auditory brainstem to investigate how axon myelinations affect the precision of sound localization. Sound waves with different interaural time differences (ITDs) are encoded and used as stimuli, and the axon properties in the network are adjusted, and the corresponding axonal conduction delays are computed with a multi-compartment axon model. Through the simulation, the sensitivity of ITD perception varies with the myelin thickness of axons in the contralateral input pathways to the medial superior olive (MSO). The ITD perception becomes more precise when the contralateral inhibitory input propagates faster than the contralateral excitatory input. These results indicate that axon myelination and contralateral spike timing influence spatial hearing perception.

Oxytocin modulates neural processing of mitral/tufted cells in the olfactory bulb.

AIM: Oxytocin plays an important role in social recognition in rodents, which is mediated predominantly by the olfactory system. Although oxytocin modulates neural activity in the olfactory bulb, the underlying mechanism is largely unknown. Here, we studied how direct infusion of oxytocin into the olfactory bulb affect social interactions in mice and modulate the neural activity of mitral/tufted cells in the olfactory bulb. METHODS: A three-chamber social interaction test was used in the behavioural test. For in vivo studies, single unit recordings, local field potential recordings and fibre photometry recordings were used to record the neural activity of olfactory bulb. For in vitro studies, we performed patch clamp recordings in the slice of the olfactory bulb. RESULTS: Behaviourally, direct oxytocin infusion in olfactory bulb increased performance in a social interaction task. Moreover, odour-evoked responses of mitral/tufted cells and neural discrimination of odours were both enhanced by oxytocin, whereas the spontaneous firing rate of mitral/tufted cells was reduced. At the neural network level, oxytocin decreased the amplitude of odour-evoked high gamma responses. At the cell population level, oxytocin decreased odour-evoked calcium responses (reflecting neural activity) specifically in granule cells. Moreover, in vitro slice recordings revealed that the inhibitory effect of oxytocin on mitral cell activity is mediated mainly by modulation of ATP-sensitive potassium channels and involves the oxytocin receptor-Gq-PLC-IP3 signalling pathway. CONCLUSION: Oxytocin modulates social interaction, likely by increasing the signal-to-noise ratio of odour responses in mitral cells which is partly through ATP-sensitive potassium channel.