Skin-Inspired All-Natural Biogel for Bioadhesive Interface.

Natural material-based hydrogels are considered ideal candidates for constructing robust bio-interfaces due to their environmentally sustainable nature and biocompatibility. However, these hydrogels often encounter limitations such as weak mechanical strength, low water resistance, and poor ionic conductivity. Here, inspired by the role of natural moisturizing factor (NMF) in skin, a straightforward yet versatile strategy is proposed for fabricating all-natural ionic biogels that exhibit high resilience, ionic conductivity, resistance to dehydration, and complete degradability, without necessitating any chemical modification. A well-balanced combination of gelatin and sodium pyrrolidone carboxylic acid (an NMF compound) gives rise to a significant enhancement in the mechanical strength, ionic conductivity, and water retention capacity of the biogel compared to pure gelatin hydrogel. The biogel manifests temperature-controlled reversible fluid-gel transition properties attributed to the triple-helix junctions of gelatin, which enables in situ gelation on diverse substrates, thereby ensuring conformal contact and dynamic compliance with curved surfaces. Due to its salutary properties, the biogel can serve as an effective and biocompatible interface for high-quality and long-term electrophysiological signal recording. These findings provide a general and scalable approach for designing natural material-based hydrogels with tailored functionalities to meet diverse application needs.

A cardiomyocyte-based biosensing platform for dynamic and quantitative investigation of excessive autophagy.

Autophagy is an important physiological phenomenon in eukaryotes that helps maintain the cellular homeostasis. Autophagy is involved in the development of various cardiovascular diseases, affecting the maintenance of cardiac function and disease prognosis. Physiological levels of autophagy serve as a defense mechanism for cardiomyocytes against environmental stimuli, but an overabundance of autophagy may contribute to the development of cardiovascular diseases. However, conventional biological methods are difficult to monitor the autophagy process in a dynamic and chronic manner. Here, we developed a cardiomyocyte-based biosensing platform that records electrophysiological evolutions in action potentials to reflect the degree of autophagy. Different concentrations of rapamycin-mediated autophagy were administrated in the culture environment to simulate the autophagy model. Moreover, the 3-methyladenine (3-MA)-mediated autophagy inhibition was also investigated the protection on the autophagy. The recorded action potentials can precisely reflect different degrees of autophagy. Our study confirms the possibility of visualizing and characterizing the process of cardiomyocyte autophagy using cardiomyocyte-based biosensing platform, allowing to monitor the whole autophagy process in a non-invasive, real-time, and continuous way. We believe it will pave a promising avenue to precisely study the autophagy-related cardiovascular diseases.

Basal Forebrain Modulation of Olfactory Coding In Vivo.

Sensory perception is one of the most fundamental brain functions, allowing individuals to properly interact and adapt to a constantly changing environment. This process requires the integration of bottom-up and topdown neuronal activity, which is centrally mediated by the basal forebrain, a brain region that has been linked to a series of cognitive processes such as attention and alertness. Here, we review the latest research using optogenetic approaches in rodents and in vivo electrophysiological recordings that are shedding light on the role of this region, in regulating olfactory processing and decisionmaking. Moreover, we summarize evidence highlighting the anatomical and physiological differences in the basal forebrain of individuals with autism spectrum disorder, which could underpin the sensory perception abnormalities they exhibit, and propose this research line as a potential opportunity to understand the neurobiological basis of this disorder.

La percepción sensorial es una de las funciones cerebrales más fundamentales, permitiendo a los individuos interactuar de manera apropiada con el entorno y adaptarse a un ambiente en constante cambio. Este proceso requiere la integración de la actividad neuronal ascendente y descendente, que es mediada por el cerebro basal (BF), una región cerebral que ha sido asociada a una serie de procesos cognitivos, como estados de atención y alerta.En este trabajo revisamos las últimas investigaciones que han utilizado optogenética y registros electrofisiológicos in vivo que han iluminado el rol del BF en el procesamiento olfatorio y la toma de decisiones. Además, resumimos la literatura que destaca las alteraciones fisiológicas y anatómicas del BF de individuos con trastornos del espectro autista, que podrían subyacer las anormalidades en la percepción que presentan, y proponemos esta línea de investigación como una posible oportunidad para entender las bases neurobiológicas de este trastorno.

Etomidate Depresses Spontaneous Complex Spikes Activity of Cerebellar Purkinje Cells via Cannabinoid 1 Receptor in vivo in Mice.

INTRODUCTION: Complex spikes (CSs) activity of cerebellar Purkinje cells plays critical roles in motor coordination and motor learning by transferring information to cerebellar cortex, which is an accessible and useful model for neurophysiological investigation. Etomidate is an ultrashort-acting nonbarbiturate intravenous anesthetic, which inhibits the spontaneous activity of cerebellar Purkinje cells through activation of GABAA and glycine receptors in vivo in mice. However, the effect of etomidate on the spontaneous CSs activity of cerebellar Purkinje cells in living mouse is not clear. METHODS: We here investigated the effects of etomidate on spontaneous CSs activity of cerebellar Purkinje cell in urethane-anesthetized mice by electrophysiology recording technique and pharmacological methods. RESULTS: Our results showed that cerebellar surface perfusion of etomidate significantly depressed the activity of spontaneous CSs, which exhibited decreases in the number of spikelets and the area under curve (AUC) of the CSs. The etomidate-produced inhibition of CSs activity was persisted in the presence of GABAA and glycine receptors antagonists. However, application of cannabinoid 1 (CB1) receptor antagonist, AM-251, completely blocked the etomidate-induced inhibition of CSs. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease of CSs. Moreover, in the presence of a specific protein kinase A (PKA) inhibitor, KT5720, etomidate failed to produce decreases in the spikelets number and the AUC of the spontaneous CSs. CONCLUSION: These results indicate that cerebellar surface application of etomidate facilitates CB1 receptor activity resulting in a depression of spontaneous CSs activity of Purkinje cells via PKA signaling pathway in mouse cerebellar cortex. Our present results suggest that the etomidate administration may impair the function of cerebellar cortical neuronal circuitry by inhibition of the climbing fiber - Purkinje cells synaptic transmission through activation of CB1 receptors in vivo in mice.

Recent strategies for neural dynamics observation at a larger scale and wider scope.

The tremendous technical progress in neuroscience offers opportunities to observe a more minor or/and broader dynamic picture of the brain. Moreover, the large-scale neural activity of individual neurons enables the dissection of detailed mechanistic links between neural populations and behaviors. To measure neural activity in-vivo, multi-neuron recording, and neuroimaging techniques are employed and developed to acquire more neurons. The tools introduced concurrently recorded dozens to hundreds of neurons in the coordinated brain regions and elucidated the neuronal ensembles from a massive population perspective of diverse neurons at cellular resolution. In particular, the increasing spatiotemporal resolution of neuronal monitoring across the whole brain dramatically facilitates our understanding of additional nervous system functions in health and disease. Here, we will introduce state-of-the-art neuroscience tools involving large-scale neural population recording and the long-range connections spanning multiple brain regions. Their synergic effects provide to clarify the controversial circuitry underlying neuroscience. These challenging neural tools present a promising outlook for the fundamental dynamic interplay across levels of synaptic cellular, circuit organization, and brain-wide. Hence, more observations of neural dynamics will provide more clues to elucidate brain functions and push forward innovative technology at the intersection of neural engineering disciplines. We hope this review will provide insight into the use or development of recent neural techniques considering spatiotemporal scales of brain observation.

Development of a synchronous recording and photo-stimulating electrode in multiple brain neurons.

The investigation of brain networks and neural circuits involves the crucial aspects of observing and modulating neurophysiological activity. Recently, opto-electrodes have emerged as an efficient tool for electrophysiological recording and optogenetic stimulation, which has greatly facilitated the analysis of neural coding. However, implantation and electrode weight control have posed significant challenges in achieving long-term and multi-regional brain recording and stimulation. To address this issue, we have developed a mold and custom-printed circuit board-based opto-electrode. We report successful opto-electrode placement and high-quality electrophysiological recordings from the default mode network (DMN) of the mouse brain. This novel opto-electrode facilitates synchronous recording and stimulation in multiple brain regions and holds promise for advancing future research on neural circuits and networks.

Abnormal Spontaneous Discharges of Primary Sensory Neurons and Pain Behavior in a Rat Model of Vascular Dementia.

Patients with vascular dementia experience more pain than healthy elders, potentially due to the presence of central neuropathic pain. However, the mechanisms underlying neuropathic pain in vascular dementia remain poorly understood, and there is currently a lack of effective treatment available. In this study, a rat model of vascular dementia was induced by permanently occluding the common carotid arteries bilaterally (2-VO). The cognitive impairments in the 2-VO rats were evaluated using the Morris Water Maze test, while HE and LBF staining were employed to assess brain tissue lesions in the hippocampal, cerebral cortex, and white matter regions known to be associated with severe memory and learning deficits. Furthermore, pain-related behavioral tests, including mechanical and thermal stimuli assessments, were conducted, and in vivo electrophysiological recordings of primary sensory neurons were performed. Compared to sham-operated and pre-operative rats, rats with vascular dementia exhibited mechanical allodynia and thermal hyperalgesia 30 days after surgery. Furthermore, in vivo electrophysiology revealed a significant increase in the occurrence of spontaneous activity of Aß- and C-fiber sensory neurons in the rat model of vascular dementia. These results indicate that neuropathic pain behaviors developed in the rat model of vascular dementia, and abnormal spontaneous discharges of primary sensory neurons may play a crucial role in the development of pain after vascular dementia.

Patrones clínicos y neurofisiológicos de presentación temprana en la polirradiculoneuropatía inflamatoria desmielinizante crónica de inicio agudo / Clinical and neurophysiological patterns of early presenting symptoms in acute onset chronic inflammatory demyelinating polyradiculoneuropathy

Introducción: Dentro de los fenotipos de polineuropatía desmielinizante inflamatoria crónica (CIDP) existe uno cuyo tiempo de evolución es menor de ocho semanas desde el inicio de los síntomas, denominado de inicio agudo (A-CIDP). Esta entidad puede confundirse con el síndrome de Guillain-Barré, variedad desmielinizante inflamatoria aguda (AIDP), lo que retrasa el inicio del tratamiento. Objetivo: Analizar las diferencias clínicas y electrofisiológicas entre A-CIDP, CIDP clásica y AIDP, con el fin de identificar factores que auxilien al diagnóstico diferencial de forma temprana. Pacientes y métodos: Se realizó un estudio transversal con pacientes atendidos en la clínica de enfermedades neuromusculares del Instituto Nacional de Neurología y Neurocirugía con diagnóstico de CIDP según criterios de la European Federation of Neurological Societies and Peripheral Nerve Society. Los pacientes con CIDP <8 semanas se catalogaron como A-CIDP y fueron comparados con pacientes diagnosticados con CIDP clásica y AIDP. Se obtuvieron y analizaron variables clínicas, paraclínicas y electrofisiológicas. Resultados: Se observaron diferencias significativas en antecedente de infección, afección de nervios del cráneo y disautonomías entre la A-CIDP y la AIDP. Los registros electrofisiológicos describieron diferencias significativas en velocidad de conducción de los nervios motores y en los registros del nervio sural, que fueron menores en el grupo de A-CIDP. Conclusión: El antecedente de infección, la afección de nervios del cráneo y las disautonomías son parámetros importantes que se debe tener en cuenta para el diagnóstico diferencial de estas entidades. El análisis electrofisiológico es similar entre la A-CIDP y la CIDP. El diagnóstico diferencial entre estos tipos de polineuropatía desmielinizante debe basarse en el juicio clínico.(AU)

Introduction: The phenotypes of chronic inflammatory demyelinating polyneuropathy (CIDP) include an acute-onset phenotype (A-CIDP) with an evolution time of less than eight weeks from the onset of symptoms. This entity can be confused with Guillain-Barré syndrome of the acute inflammatory demyelinating variety (AIDP), delaying the start of treatment. Objective: To analyze the clinical and electrophysiological differences between A-CIDP, classic CIDP and AIDP, in order to identify factors that may help in the early differential diagnosis. Patients and methods: A cross-sectional study was carried out with patients seen at the neuromuscular disease clinic of the National Institute of Neurology and Neurosurgery with a diagnosis of CIDP according to the criteria of the European Federation of Neurological Societies and Peripheral Nerve Society. Patients with CIDP <8 weeks were categorized as A-CIDP and were compared with patients diagnosed with classic CIDP and AIDP. Clinical, paraclinical and electrophysiological variables were obtained and analyzed. Results: Significant differences in history of infection, cranial nerve involvement and dysautonomia were observed between A-CIDP and AIDP. Electrophysiological recordings reported significant differences in motor nerve conduction velocity and sural nerve recordings, being lower in the A-CIDP group. Conclusion: A history of infection, cranial nerve involvement and dysautonomia are important parameters to take into account for the differential diagnosis of these entities. Electrophysiological analysis is similar between A-CIDP and CIDP. The differential diagnosis between these types of demyelinating polyneuropathy must be based on clinical assessment.(AU)

3D Printed Skull Cap and Benchtop Fabricated Microwire-Based Microelectrode Array for Custom Rat Brain Recordings.

Microwire microelectrode arrays (MEAs) have been a popular low-cost tool for chronic electrophysiological recordings and are an inexpensive means to record the electrical dynamics crucial to brain function. However, both the fabrication and implantation procedures for multi-MEAs on a single rodent are time-consuming and the accuracy and quality are highly manual skill-dependent. To address the fabrication and implantation challenges for microwire MEAs, (1) a computer-aided designed and 3D printed skull cap for the pre-determined implantation locations of each MEA and (2) a benchtop fabrication approach for low-cost custom microwire MEAs were developed. A proof-of-concept design of a 32-channel 4-MEA (8-wire each) recording system was prototyped and tested through Sprague Dawley rat recordings. The skull cap design, based on the CT-scan of a single rat conforms well with multiple Sprague Dawley rats of various sizes, ages, and weight with a minimal bregma alignment error (A/P axis standard error of the mean = 0.25 mm, M/L axis standard error of the mean = 0.07 mm, n = 6). The prototyped 32-channel system was able to record the spiking activities over five months. The developed benchtop fabrication method and the 3D printed skull cap implantation platform would enable neuroscience groups to conduct in-house design, fabrication, and implantation of customizable microwire MEAs at a lower cost than the current commercial options and experience a shorter lead time for the design modifications and iterations.

High-Performance Flexible Microneedle Array as a Low-Impedance Surface Biopotential Dry Electrode for Wearable Electrophysiological Recording and Polysomnography.

HIGHLIGHTS: Polyimide-based flexible microneedle array (PI-MNA) electrodes realize high electrical/mechanical performance and are compatible with wearable wireless recording systems. The normalized electrode-skin interface impedance (EII) of the PI-MNA electrodes reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, approximately 1/250 of clinical standard electrodes. This is the first report on the clinical study of microneedle electrodes. The PI-MNA electrodes are applied to clinical long-term continuous monitoring for polysomnography. Microneedle array (MNA) electrodes are an effective solution to achieve high-quality surface biopotential recording without the coordination of conductive gel and are thus very suitable for long-term wearable applications. Existing schemes are limited by flexibility, biosafety, and manufacturing costs, which create large barriers for wider applications. Here, we present a novel flexible MNA electrode that can simultaneously achieve flexibility of the substrate to fit a curved body surface, robustness of microneedles to penetrate the skin without fracture, and a simplified process to allow mass production. The compatibility with wearable wireless systems and the short preparation time of the electrodes significantly improves the comfort and convenience of electrophysiological recording. The normalized electrode-skin contact impedance reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, a record low value compared to previous reports and approximately 1/250 of the standard electrodes. The morphology, biosafety, and electrical/mechanical properties are fully characterized, and wearable recordings with a high signal-to-noise ratio and low motion artifacts are realized. The first reported clinical study of microneedle electrodes for surface electrophysiological monitoring was conducted in tens of healthy and sleep-disordered subjects with 44 nights of recording (over 8 h per night), providing substantial evidence that the electrodes can be leveraged to substitute for clinical standard electrodes.

Facial Stimulation Induces Long-Term Potentiation of Mossy Fiber-Granule Cell Synaptic Transmission via GluN2A-Containing N-Methyl-D-Aspartate Receptor/Nitric Oxide Cascade in the Mouse Cerebellum.

Long-term synaptic plasticity in the cerebellar cortex is a possible mechanism for motor learning. Previous studies have demonstrated the induction of mossy fiber-granule cell (MF-GrC) synaptic plasticity under in vitro and in vivo conditions, but the mechanisms underlying sensory stimulation-evoked long-term synaptic plasticity of MF-GrC in living animals are unclear. In this study, we investigated the mechanism of long-term potentiation (LTP) of MF-GrC synaptic transmission in the cerebellum induced by train of facial stimulation at 20 Hz in urethane-anesthetized mice using electrophysiological recording, immunohistochemistry techniques, and pharmacological methods. Blockade of GABAA receptor activity and repetitive facial stimulation at 20 Hz (240 pulses) induced an LTP of MF-GrC synapses in the mouse cerebellar cortical folium Crus II, accompanied with a decrease in paired-pulse ratio (N2/N1). The facial stimulation-induced MF-GrC LTP was abolished by either an N-methyl-D-aspartate (NMDA) receptor blocker, i.e., D-APV, or a specific GluNR2A subunit-containing NMDA receptor antagonist, PEAQX, but was not prevented by selective GluNR2B or GluNR2C/D subunit-containing NMDA receptor blockers. Application of GNE-0723, a selective and brain-penetrant-positive allosteric modulator of GluN2A subunit-containing NMDA receptors, produced an LTP of N1, accompanied with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. Inhibition of nitric oxide synthesis (NOS) prevented the facial stimulation-induced MF-GrC LTP, while activation of NOS produced an LTP of N1, with a decrease in N2/N1 ratio, and occluded the 20-Hz facial stimulation-induced MF-GrC LTP. In addition, GluN2A-containing NMDA receptor immunoreactivity was observed in the mouse cerebellar granular layer. These results indicate that facial stimulation at 20 Hz induced LTP of MF-GrC synaptic transmission via the GluN2A-containing NMDA receptor/nitric oxide cascade in mice. The results suggest that the sensory stimulation-evoked LTP of MF-GrC synaptic transmission in the granular layer may play a critical role in cerebellar adaptation to native mossy fiber excitatory inputs and motor learning behavior in living animals.

A universal, multimodal cell-based biosensing platform for optimal intracellular action potential recording.

Intracellular recording of action potentials is an essential mean for studying disease mechanisms, and for electrophysiological studies, particularly in excitable cells as cardiomyocytes or neurons. Current strategies to obtain intracellular recordings include three-dimensional (3D) nanoelectrodes that can effectively penetrate the cell membrane and achieve high-quality intracellular recordings in a minimally invasive manner, or transient electroporation of the membrane that can yield temporary intracellular access. However, the former strategy requires a complicated and costly fabrication process, and the latter strategy suffers from high dependency on the method of application of electroporation, yielding inconsistent, suboptimal recordings. These factors hinder the high throughput use of these strategies in electrophysiological studies. In this work, we propose an advanced cell-based biosensing platform that relies on electroporation to produce consistent, high-quality intracellular recordings. The suggested universal system can be integrated with any electrode array, and it enables tunable electroporation with controllable pulse parameters, while the recorded potentials can be analyzed in real time to provide instantaneous feedback on the electroporation effectiveness. This integrated system enables the user to perform electroporation, record and assess the obtained signals in a facile manner, to ultimately achieve stable, reliable, intracellular recording. Moreover, the proposed platform relies on microelectrode arrays which are suited for large-scale production, and additional modules that are low-cost. Using this platform, we demonstrate the tuning of electroporation pulse width, pulse number, and amplitude, to achieve effective electroporation and high-quality intracellular recordings. This integrated platform has the potential to enable larger scale, repeatable, convenient, and low-cost electrophysiological studies.

Activation CRF-R2 augments cerebellar climbing fiber-Purkinje cell synaptic transmission via presynaptic PKA pathway in mice.

Corticotropin releasing factor (CRF) type 2 receptor (CRF-R2) is present in climbing fiber (CF) afferents, which involves in modulating the CF-Purkinje cell (PC) synaptic transmission in cerebellar cortex. However, the role of CRF-R2 in regulating CF-PC synaptic transmission is unclear. We here investigate the role of CRF-R2 in modulating PC complex spikes (CSs) activity and CF-PC synaptic transmission using electrophysiological recording techniques and pharmacological methods. Cerebellar surface application of a selective CRF-R2 agonist, urocortin III (UCN III; 300 nM) induced an enhancement of CSs activity, which expressed an increase in number of CSs spikelets and pause of simple spike firing of cerebellar PCs in urethane anesthetized mice. The CSs activity was also enhanced by CRF (300 nM) in the presence of CRF-R1 antagonist, which was abolished by CRF-R2 antagonist. Under in vitro conditions, bath application of UCN III increased CF-PC synaptic transmission, which exhibited a time-dependent increase in amplitude of excitatory postsynaptic currents (EPSCs), accompanied by a decrease in paired-pulse ratio (PPR). In addition, bath application of CRF (100 nM) induced an increase in amplitude of EPSCs and a decrease in PPR in the absence of CRF-R1 activity. UCN-induced enhancement of CF-PC synaptic transmission was abolished by bath application of protein kinase A (PKA) inhibitor, KT5720 (100 nM), but it was not prevented by inhibiting intracellular PKA with PKI (5 µM). These results indicate that activation of CRF-R2 augments CF-PC synaptic transmission through a presynaptic PKA signaling pathway in the mouse cerebellar cortex.

Low-cost and easy-fabrication lightweight drivable electrode array for multiple-regions electrophysiological recording in free-moving mice.

Objective.Extracellular electrophysiology has been widely applied to neural circuit dissections. However, long-term multiregional recording in free-moving mice remains a challenge. Low-cost and easy-fabrication of elaborate drivable electrodes is required for their prevalence.Approach.A three-layer nested construct (outside diameter, OD ∼ 1.80 mm, length ∼10 mm, <0.1 g) was recruited as a drivable component, which consisted of an ethylene-vinyl acetate copolymer heat-shrinkable tube, non-closed loop ceramic bushing, and stainless ferrule with a bulge twining silver wire. The supporting and working components were equipped with drivable components to be assembled into a drivable microwire electrode array with a nested structure (drivable MEANS). Two drivable microwire electrode arrays were independently implanted for chronic recording in different brain areas at respective angles. An optic fiber was easily loaded into the drivable MEANS to achieve optogenetic modulation and electrophysiological recording simultaneously.Main results.The drivable MEANS had lightweight (∼0.37 g), small (∼15 mm × 15 mm × 4 mm), and low cost (⩽$64.62). Two drivable MEANS were simultaneously implanted in mice, and high-quality electrophysiological recordings could be applied ⩾5 months after implantation in freely behaving animals. Electrophysiological recordings and analysis of the lateral septum (LS) and lateral hypothalamus in food-seeking behavior demonstrated that our drivable MEANS can be used to dissect the function of neural circuits. An optical fiber-integrated drivable MEANS (∼0.47 g) was used to stimulate and record LS neurons, which suggested that changes in working components can achieve more functions than electrophysiological recordings, such as optical stimulation, drug release, and calcium imaging.Significance.Drivable MEANS is an easily fabricated, lightweight drivable microwire electrode array for multiple-region electrophysiological recording in free-moving mice. Our design is likely to be a valuable platform for both current and prospective users, as well as for developers of multifunctional electrodes for free-moving mice.

Ablation of microRNAs in VIP+ interneurons impairs olfactory discrimination and decreases neural activity in the olfactory bulb.

AIM: MicroRNAs (miRNAs) are abundantly expressed in vasoactive intestinal peptide expressing (VIP+ ) interneurons and are indispensable for their functional maintenance and survival. Here, we blocked miRNA biogenesis in postmitotic VIP+ interneurons in mice by selectively ablating Dicer, an enzyme essential for miRNA maturation, to study whether ablation of VIP+ miRNA affects olfactory function and neural activity in olfactory centres such as the olfactory bulb, which contains a large number of VIP+ interneurons. METHODS: A go/no-go odour discrimination task and a food-seeking test were used to assess olfactory discrimination and olfactory detection. In vivo electrophysiological techniques were used to record single units and local field potentials. RESULTS: Olfactory detection and olfactory discrimination behaviours were impaired in VIP+ -specific Dicer-knockout mice. In vivo electrophysiological recordings in awake, head-fixed mice showed that both spontaneous and odour-evoked firing rates were decreased in mitral/tufted cells in knockout mice. The power of ongoing and odour-evoked beta local field potentials response of the olfactory bulb and anterior piriform cortex were dramatically decreased. Furthermore, the coherence of theta oscillations between the olfactory bulb and anterior piriform cortex was decreased. Importantly, Dicer knockout restricted to olfactory bulb VIP+ interneurons recapitulated the behavioural and electrophysiological results of the global knockout. CONCLUSIONS: VIP+ miRNAs are an important factor in sensory processing, affecting olfactory function and olfactory neural activity.

Removing ocular artifacts from magnetoencephalographic data on naturalistic reading of continuous texts.

Naturalistic reading paradigms and stimuli consisting of long continuous texts are essential for characterizing the cortical basis of reading. Due to the highly dynamic nature of the reading process, electrophysiological brain imaging methods with high spatial and temporal resolution, such as magnetoencephalography (MEG), are ideal for tracking them. However, as electrophysiological recordings are sensitive to electromagnetic artifacts, data recorded during naturalistic reading is confounded by ocular artifacts. In this study, we evaluate two different pipelines for removing ocular artifacts from MEG data collected during continuous, naturalistic reading, with the focus on saccades and blinks. Both pipeline alternatives are based on blind source separation methods but differ fundamentally in their approach. The first alternative is a multi-part process, in which saccades are first extracted by applying Second-Order Blind Identification (SOBI) and, subsequently, FastICA is used to extract blinks. The other alternative uses a single powerful method, Adaptive Mixture ICA (AMICA), to remove all artifact types at once. The pipelines were tested, and their effects compared on MEG data recorded from 13 subjects in a naturalistic reading task where the subjects read texts with the length of multiple pages. Both pipelines performed well, extracting the artifacts in a single component per artifact type in most subjects. Signal power was reduced across the whole cortex in all studied frequency bands from 1 to 90 Hz, but especially in the frontal cortex and temporal pole. The results were largely similar for the two pipelines, with the exception that SOBI-FastICA reduced signal in the right frontal cortex in all studied frequency bands more than AMICA. However, there was considerable interindividual variation in the effects of the pipelines. As a holistic conclusion, we choose to recommend AMICA for removing artifacts from MEG data on naturalistic reading but note that the SOBI-FastICA pipeline has also various favorable characteristics.

New monoamine antidepressant, hypidone hydrochloride (YL-0919), enhances the excitability of medial prefrontal cortex in mice via a neural disinhibition mechanism.

Hypidone hydrochloride (YL-0919) is a novel antidepressant in clinical phase II trial. Previous studies show that YL-0919 is a selective 5-HT (serotonin) reuptake inhibitor, 5-HT1A receptor partial agonist, and 5-HT6 receptor agonist, which exerts antidepressant effects in various animal models, but its effects on neural function remain unclear. Medial prefrontal cortex (mPFC), a highly evolved brain region, controls highest order cognitive functions and emotion regulation. In this study we investigated the effects of YL-0919 on the mPFC function, including the changes in neuronal activities using electrophysiological recordings. Extracellular recording (in vivo) showed that chronic administration of YL-0919 significantly increased the spontaneous discharges of mPFC neurons. In mouse mPFC slices, whole-cell recording revealed that perfusion of YL-0919 significantly increased the frequency of sEPSCs, but decreased the frequency of sIPSCs. Then we conducted whole-cell recording in mPFC slices of GAD67-GFP transgenic mice, and demonstrated that YL-0919 significantly inhibited the excitability of GABAergic neurons. In contrast, it did not alter the excitability of pyramidal neurons in mPFC slices of normal mice. Moreover, the inhibition of GABAergic neurons by YL-0919 was prevented by pre-treatment with 5-HT1A receptor antagonist WAY 100635. Finally, chronic administration of YL-0919 significantly increased the phosphorylation levels of mTOR and GSK-3ß in the mPFC as compared with vehicle. Taken together, our results demonstrate that YL-0919 enhances the excitability of mPFC via a disinhibition mechanism to fulfill its rapid antidepressant neural mechanism, which was accomplished by 5-HT1A receptor-mediated inhibition of inhibitory GABAergic interneurons.

Acid-sensing ion channel 1a in the central nucleus of the amygdala regulates anxiety-like behaviors in a mouse model of acute pain.

Pain is commonly comorbid with anxiety; however, the neural and molecular mechanisms underlying the comorbid anxiety symptoms in pain (CASP) have not been fully elucidated. In this study, we explored the role of acid-sensing ion channel 1a (ASIC1a), located in GABAergic neurons from the central nucleus of the amygdala (GABACeA), in the regulation of CASP in an acute pain mouse model. We found that the mice displayed significant mechanical pain sensitization and anxiety-like behaviors one day post injection of complete Freud's adjuvant (CFA1D). Electrophysiological recordings from acute brain slices showed that the activity of GABACeA neurons increased in the CFA1D mice compared with that in the saline mice. In addition, chemogenetic inhibition of GABACeA neurons relieved mechanical pain sensitization and anxiety-like behaviors in the CFA1D mice. Interestingly, through pharmacological inhibition and genetic knockdown of ASIC1a in the central nucleus amygdala, we found that downregulation of ASIC1a relieved the hypersensitization of mechanical stimuli and alleviated anxiety-related behaviors, accompanied with reversing the hyperactivity of GABACeA neurons in the CFA 1D mice. In conclusion, our results provide novel insights that ASIC1a in GABACeA neurons regulates anxiety-like behaviors in a mouse model of acute pain.

Nanofibrous PEDOT-Carbon Composite on Flexible Probes for Soft Neural Interfacing.

In this study, we report a flexible implantable 4-channel microelectrode probe coated with highly porous and robust nanocomposite of poly (3,4-ethylenedioxythiophene) (PEDOT) and carbon nanofiber (CNF) as a solid doping template for high-performance in vivo neuronal recording and stimulation. A simple yet well-controlled deposition strategy was developed via in situ electrochemical polymerization technique to create a porous network of PEDOT and CNFs on a flexible 4-channel gold microelectrode probe. Different morphological and electrochemical characterizations showed that they exhibit remarkable and superior electrochemical properties, yielding microelectrodes combining high surface area, low impedance (16.8 ± 2 MΩ µm2 at 1 kHz) and elevated charge injection capabilities (7.6 ± 1.3 mC/cm2) that exceed those of pure and composite PEDOT layers. In addition, the PEDOT-CNF composite electrode exhibited extended biphasic charge cycle endurance and excellent performance under accelerated lifetime testing, resulting in a negligible physical delamination and/or degradation for long periods of electrical stimulation. In vitro testing on mouse brain slices showed that they can record spontaneous oscillatory field potentials as well as single-unit action potentials and allow to safely deliver electrical stimulation for evoking field potentials. The combined superior electrical properties, durability and 3D microstructure topology of the PEDOT-CNF composite electrodes demonstrate outstanding potential for developing future neural surface interfacing applications.