Dexmedetomidine Promotes NREM Sleep by Depressing Oxytocin Neurons in the Paraventricular Nucleus in Mice.

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVNOXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVNOXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVNOXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVNOXT neurons through α2-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVNOXT neurons through the α2-adrenoceptor.

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.

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.

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.

A Multichannel Flexible Optoelectronic Fiber Device for Distributed Implantable Neurological Stimulation and Monitoring.

Optical fibers made of polymeric materials possess high flexibility that can potentially integrate with flexible electronic devices to realize complex functions in biology and neurology. Here, a multichannel flexible device based on four individually addressable optical fibers transfer-printed with flexible electronic components and controlled by a wireless circuit is developed. The resulting device offers excellent mechanics that is compatible with soft and curvilinear tissues, and excellent diversity through switching different light sources. The combined configuration of optical fibers and flexible electronics allows optical stimulation in selective wavelengths guided by the optical fibers, while conducting distributed, high-throughput biopotential sensing using the flexible microelectrode arrays. The device has been demonstrated in vivo with rats through optical stimulation and simultaneously monitoring of spontaneous/evoked spike signals and local field potentials using 32 microelectrodes in four brain regions. Biocompatibility of the device has been characterized by behavior and immunohistochemistry studies, demonstrating potential applications of the device in long-term animal studies. The techniques to integrate flexible electronics with optical fibers may inspire the development of more flexible optoelectronic devices for sophisticated applications in biomedicine and biology.

Rapid actions of anti-Müllerian hormone in regulating synaptic transmission and long-term synaptic plasticity in the hippocampus.

Anti-Müllerian hormone (Amh) is a peptide factor that is known to regulate sexual differentiation and gonadal function in mammals. Although Amh is also suggested to be associated with cognitive development and function in the postnatal brain, little is known about its expression or direct effects on neuronal activities in the hippocampus. Therefore, we assessed Amh and its receptor expression in the hippocampus of male and female mice using PCR, Western blot, and immunofluorescence staining. While Amh-specific receptor expression was comparable between males and females, mRNA and protein levels of Amh were higher in females than those of males. Electrophysiological recordings on acute hippocampal slices showed that exogenous Amh protein addition increased synaptic transmission and long-term synaptic plasticity at the Cornu Ammonis (CA) 3-CA1 synapses. Amh exposure also increased the excitatory postsynaptic potential at CA1 synapses. Our findings support direct and rapid actions of Amh as a paracrine and/or autocrine factor in regulating hippocampal neuronal activities. Data provide functional evidence of Amh-mediated postsynaptic modulation of synaptic transmission and Amh-regulated long-term synaptic plasticity in the hippocampus. These results suggest a potential role of Amh in learning and memory, and a possible cause of the sex differences in cognitive development and function.

Soft conductive micropillar electrode arrays for biologically relevant electrophysiological recording.

Multielectrode arrays (MEAs) are essential tools in neural and cardiac research as they provide a means for noninvasive, multiplexed recording of extracellular field potentials with high temporal resolution. To date, the mechanical properties of the electrode material, e.g., its Young's modulus, have not been taken into consideration in most MEA designs leaving hard materials as the default choice due to their established fabrication processes. However, the cell-electrode interface is known to significantly affect some aspects of the cell's behavior. In this paper, we describe the fabrication of a soft 3D micropillar electrode array. Using this array, we proceed to successfully record action potentials from monolayer cell cultures. Specifically, our conductive hydrogel micropillar electrode showed improved signal amplitude and signal-to-noise ratio, compared with conventional hard iridium oxide micropillar electrodes of the same diameter. Taken together, our fabricated soft micropillar electrode array will provide a tissue-like Young's modulus and thus a relevant mechanical microenvironment to fundamental cardiac and neural studies.

Migraine classification using somatosensory evoked potentials.

OBJECTIVE: The automatic detection of migraine states using electrophysiological recordings may play a key role in migraine diagnosis and early treatment. Migraineurs are characterized by a deficit of habituation in cortical information processing, causing abnormal changes of somatosensory evoked potentials. Here, we propose a machine learning approach to utilize somatosensory evoked potential-based biomarkers for migraine classification in a noninvasive setting. METHODS: Forty-two migraine patients, including 29 interictal and 13 ictal, were recruited and compared with 15 healthy volunteers of similar age and gender distribution. The right median nerve somatosensory evoked potentials were collected from all subjects. State-of-the-art machine learning algorithms including random forest, extreme gradient-boosting trees, support vector machines, K-nearest neighbors, multilayer perceptron, linear discriminant analysis, and logistic regression were used for classification and were built upon somatosensory evoked potential features in time and frequency domains. A feature selection method was employed to assess the contribution of features and compare it with previous clinical findings, and to build an optimal feature set by removing redundant features. RESULTS: Using a set of relevant features and different machine learning models, accuracies ranging from 51.2% to 72.4% were achieved for the healthy volunteers-ictal-interictal classification task. Following model and feature selection, we successfully separated the three groups of subjects with an accuracy of 89.7% for the healthy volunteers-ictal, 88.7% for healthy volunteers-interictal, 80.2% for ictal-interictal, and 73.3% for healthy volunteers-ictal-interictal classification tasks, respectively. CONCLUSION: Our proposed model suggests the potential use of somatosensory evoked potentials as a prominent and reliable signal in migraine classification. This non-invasive somatosensory evoked potential-based classification system offers the potential to reliably separate migraine patients in ictal and interictal states from healthy controls.

Improvement of fiber connectivity and functional recovery after stroke by montelukast, an available and safe anti-asthmatic drug.

Stroke is one of the main causes of death, neurological dysfunctions or disability in elderly. Neuroprotective drugs have been proposed to improve long-term recovery after stroke, but failed to reach clinical effectiveness. Hence, recent studies suggested that restorative therapies should combine neuroprotection and remyelination. Montelukast, an anti-asthmatic drug, was shown to exert neuroprotection in animal models of CNS injuries, but its ability to affect oligodendrocytes, restoring fiber connectivity, remains to be determined. In this study, we evaluated whether montelukast induces long-term repair by promoting fiber connectivity up to 8 weeks after middle cerebral artery occlusion (MCAo), using different experimental approaches such as in vivo diffusion magnetic resonance imaging (MRI), electrophysiological techniques, ex vivo diffusion tensor imaging (DTI)-based fiber tracking and immunohistochemistry. We found that, in parallel with a reduced evolution of ischemic lesion and atrophy, montelukast increased the DTI-derived axial diffusivity and number of myelin fibers, the density of myelin binding protein (MBP) and the number of GSTpi+ mature oligodendrocytes. Together with the rescue of MCAo-induced impairments of local field potentials in ischemic cortex, the data suggest that montelukast may improve fibers reorganization. Thus, to ascertain whether this effect involved changes of oligodendrocyte precursor cells (OPCs) activation and maturation, we used the reporter GPR17iCreERT2:CAG-eGreen florescent protein (GFP) mice that allowed us to trace the fate of OPCs throughout animal's life. Our results showed that montelukast enhanced the OPC recruitment and proliferation at acute phase, and increased their differentiation to mature oligodendrocytes at chronic phase after MCAo. Considering the crosstalk between OPCs and microglia has been widely reported in the context of demyelinating insults, we also assessed microglia activation. We observed that montelukast influenced the phenotype of microglial cells, increasing the number of M2 polarized microglia/macrophages, over the M1 phenotype, at acute phase after MCAo. In conclusion, we demonstrated that montelukast improves fiber re-organization and long-term functional recovery after brain ischemia, enhancing recruitment and maturation of OPCs. The present data suggest that montelukast, an already approved drug, could be "repositioned "as a protective drug in stroke acting also on fiber re-organization.

Etomidate Modulates the Tactile Stimulation-Evoked Field Potential Responses in Cerebellar Granule Cell Layer in vivo in Mice.

Etomidate (ET) produces sedation by binding on the γ-aminobutyric acid type A (GABAA) receptors. We previously found that ET inhibited cerebellar Purkinje cells activity via both GABAA and glycine receptors in vivo in mice, suggesting that ET modulated sensory information synaptic transmission in cerebellar cortex. In this study, we investigated the effect of ET on the sensory stimulation-evoked responses in the cerebellar granule layer (GL) in urethane-anesthetized mice, using electrophysiological and pharmacological methods. Our results showed that cerebellar surface perfusion of ET (100 µmol/L) significantly decreased amplitude and area under the curve (AUC) of the sensory stimulation-evoked excitatory component (N1) in the cerebellar GL. Application of GABAA receptor antagonist, SR95531 (20 µmol/L) significantly attenuated, but not abolished the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. However, application of a mixture of SR95531 (20 µmol/L) and cannabinoid 1 receptor (CB1) antagonist, AM-251 (5 µmol/L), completely blocked the ET-induced decrease in amplitude and AUC of facial stimulation-evoked responses. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease in amplitude and AUC of N1 in the absence of GABAA receptors activity, as well occluded the ET-induced depression of N1. Moreover, the ET-induced changes in amplitude and AUC of N1 in absence of GABAA receptors activity were abolished by a specific protein kinase A (PKA) inhibitor, KT5720. These results indicate that ET facilitates CB1 receptors in the absence of GABAA receptors activity, resulting in a depression of the sensory stimulation-evoked synaptic transmission via PKA signaling pathway in mouse cerebellar GL.

Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides.

Positive selection sites (PSSs), a class of amino acid sites with an excess of nonsynonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e., agent of selection). Scorpion α-toxins are a class of multigene family of peptide neurotoxins affecting voltage-gated Na(+ )(Nav) channels, whose members exhibit differential potency and preference for insect and mammalian Nav channels. In this study, we undertook a systematical molecular dissection of nearly all the PSSs newly characterized in the Mesobuthus α-toxin family and a two-residue insertion ((19)AlaPhe(20)) located within a positively selected loop via mutational analysis of α-like MeuNaTxα-5, one member affecting both insect and mammalian Nav channels. This allows to identify hot-spot residues on its functional face involved in interaction with the receptor site of Nav channels, which comprises two PSSs (Ile(40) and Leu(41)) and the small insertion, both located on two spatially separated functional loops. Mutations at these hot-spots resulted in a remarkably decreased anti-mammalian activity in MeuNaTxα-5 with partially impaired or enhanced insecticide activity, suggesting the potential of PSSs in designing promising candidate insecticides from scorpion α-like toxins. Based on an experiment-guided toxin-channel complex model and high evolutionary variability in the receptor site of predators and prey of scorpions, we provide new evidence for target-driven adaptive evolution of scorpion toxins to deal with their targets' diversity.

Methodological standards for in vitro models of epilepsy and epileptic seizures. A TASK1-WG4 report of the AES/ILAE Translational Task Force of the ILAE.

In vitro preparations are a powerful tool to explore the mechanisms and processes underlying epileptogenesis and ictogenesis. In this review, we critically review the numerous in vitro methodologies utilized in epilepsy research. We provide support for the inclusion of detailed descriptions of techniques, including often ignored parameters with unpredictable yet significant effects on study reproducibility and outcomes. In addition, we explore how recent developments in brain slice preparation relate to their use as models of epileptic activity.

New ERP Methods Tailored Onto Single Subject Neuroanatomical Variability.

Gebodh and coworkers present an innovative method for strengthening the reliability with which event-related potential (ERP) components are recorded. By tailoring the experimental design to the neuroanatomical singularity of each observer, this method provides more robust and cleaner data.

A step toward essential tremor gene discovery: identification of extreme phenotype and screening of HTRA2 and ANO3.

BACKGROUND: Essential tremor (ET) is characterized by a frequent family history. No monogenic form of ET has been identified. We aimed at exploring ET patients to identify distinct subgroups and facilitate the identification of ET genes. We tested for the presence of HTRA2 p.G399S, and ANO3 p. W490C, p. R484 W and p. S685G mutations. METHODS: Between June 2011 and November 2013, all consecutive patients suspected with ET were prospectively included in a prospective, monocentric study. Family history, age at onset (AAO), features of tremor, benefit of alcohol and drugs, electrophysiological recording findings were collected. Sanger sequencing was performed for HTRA2 and ANO3 mutations screening. RESULTS: Sixty eight patients were investigated. Fourteen diagnosed with psychogenic (5) or dystonic tremor (9) were excluded. Regarding the 54 ET patients, mean AAO was 48 years (6-77), and mean disease duration 15 years (1-55). Bimodal distribution of AAO was consistent with phenotypic subgroups. In patients with AAO before 30 years, marked benefit of alcohol (p < 0.01) and ET family history (p < 0.01) were more frequent and the disease progression less severe (p < 0.0001). Neither HTRA2 nor ANO3 mutation were identified in our patients. CONCLUSIONS: Our data support that distinct ET phenotypic subgroups may be encountered. We recommend to study separately extreme phenotypes of ET, particularly autosomal dominant families with early AAO (<30 years) and marked benefit of alcohol, to facilitate the identification of ET genes. Electromyographic recording remains a support to distinguish ET from differential diagnosis. HTRA2 and ANO3 mutations are not common causes of ET.

Spiral motion selective neurons in area MSTd contribute to judgments of heading.

Self-motion generates patterns of optic flow on the retina. Neurons in the dorsal part of the medial superior temporal area (MSTd) are selective for these optic flow patterns. It has been shown that neurons in this area that are selective for expanding optic flow fields are involved in heading judgments. We wondered how subpopulations of MSTd neurons, those tuned for expansion, rotation or spiral motion, contribute to heading perception. To investigate this question, we recorded from neurons in area MSTd with diverse tuning properties, while the animals performed a heading-discrimination task. We found a significant trial-to-trial correlation (choice probability) between the MSTd neurons and the animals' decision. Neurons in different subpopulations did not differ significantly in terms of their choice probability. Instead, choice probability was strongly related to the sensitivity of the neuron in our sample, regardless of tuning preference. We conclude that a variety of subpopulations of MSTd neurons with different tuning properties contribute to heading judgments.

Infrared detection without specialized infrared receptors in the bloodsucking bug Rhodnius prolixus.

Bloodsucking bugs use infrared radiation (IR) for locating warm-blooded hosts and are able to differentiate between infrared and temperature (T) stimuli. This paper is concerned with the neuronal coding of IR in the bug Rhodnius prolixus. Data obtained are from the warm cells in the peg-in-pit sensilla (PSw cells) and in the tapered hairs (THw cells). Both warm cells responded to oscillating changes in air T and IR with oscillations in their discharge rates. The PSw cells produced stronger responses to T oscillations than the THw cells. Oscillations in IR did the reverse: they stimulated the latter more strongly than the former. The reversal in the relative excitability of the two warm cell types provides a criterion to distinguish between changes in T and IR. The existence of strongly responsive warm cells for one or the other stimulus in a paired comparison is the distinguishing feature of a "combinatory coding" mechanism. This mechanism enables the information provided by the difference or the ratio between the response magnitudes of both cell types to be utilized by the nervous system in the neural code for T and IR. These two coding parameters remained constant, although response strength changed when the oscillation period was altered. To discriminate between changes in T and IR, two things are important: which sensory cell responded to either stimulus and how strong was the response. The label warm or infrared cell may indicate its classification, but the functions are only given in the context of activity produced in parallel sensory cells.

Electrophysiological activity pattern of mouse hippocampal CA1 and dentate gyrus under isoflurane anesthesia.

General anesthesia can impact a patient's memory and cognition by influencing hippocampal function. The CA1 and dentate gyrus (DG), serving as the primary efferent and gateway of the hippocampal trisynaptic circuit facilitating cognitive learning and memory functions, exhibit significant differences in cellular composition, molecular makeup, and responses to various stimuli. However, the effects of isoflurane-induced general anesthesia on CA1 and DG neuronal activity in mice are not well understood. In this study, utilizing electrophysiological recordings, we examined neuronal population dynamics and single-unit activity (SUA) of CA1 and DG in freely behaving mice during natural sleep and general anesthesia. Our findings reveal that isoflurane anesthesia shifts local field potential (LFP) to delta frequency and reduces the firing rate of SUA in both CA1 and DG, compared to wakefulness. Additionally, the firing rates of DG neurons are significantly lower than CA1 neurons during isoflurane anesthesia, and the recovery of theta power is slower in DG than in CA1 during the transition from anesthesia to wakefulness, indicating a stronger and more prolonged impact of isoflurane anesthesia on DG. This work presents a suitable approach for studying brain activities during general anesthesia and provides evidence for distinct effects of isoflurane anesthesia on hippocampal subregions.

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.

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.

Ultrasoft Long-Lasting Reusable Hydrogel-Based Sensor Patch for Biosignal Recording.

Here, we report an ultrasoft extra long-lasting, reusable hydrogel-based sensor that enables high-quality electrophysiological recording with low-motion artifacts. The developed sensor can be used and stored in an ambient environment for months before being reused. The developed sensor is made of a self-adhesive electrical-conductivity-enhanced ultrasoft hydrogel mounted in an Ecoflex-based frame. The hydrogel's conductivity was enhanced by incorporating polypyrrole (PPy), resulting in a conductivity of 0.25 S m-1. Young's modulus of the sensor is only 12.9 kPa, and it is stretchable up to 190%. The sensor was successfully used for electrocardiography (ECG) and electromyography (EMG). Our results indicate that using the developed hydrogel-based sensor, the signal-to-noise ratio of recorded electrophysiological signals was improved in comparison to that when medical-grade silver/silver chloride (Ag/AgCl) wet gel electrodes were used (33.55 dB in comparison to 22.16 dB). Due to the ultra-softness, high stretchability, and self-adhesion of the developed sensor, it can conform to the skin and, therefore, shows low susceptibility to motion. In addition, the sensor shows no sign of irritation or allergic reaction, which usually occurs after long-term wearing of medical-grade Ag/AgCl wet gel electrodes on the skin. Further, the sensor is fabricated using a low-cost and scalable fabrication process.