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Objective: Genetic variations in proteins of the mechanistic target of rapamycin (mTOR) pathway cause a spectrum of neurodevelopmental disorders often associated with brain malformations and with intractable epilepsy. The mTORopathies are characterized by hyperactive mTOR pathway and comprise tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type II. How hyperactive mTOR translates into abnormal neuronal activity and hypersynchronous network remains to be better understood. Previously, the role of upregulated GluN2C‐containing glutamate‐gated N‐methyl‐D‐aspartate receptors (NMDARs) has been demonstrated for germline defects in the TSC genes. Here, we questioned whether this mechanism would expand to other mTORopathies in the different context of a somatic genetic variation of the MTOR protein recurrently found in FCD type II. Methods: We used a rat model of FCD created by in utero electroporation of neural progenitors of dorsal telencephalon with expression vectors encoding either the wild‐type or the pathogenic MTOR variant (p.S2215F). In this mosaic configuration, patch‐clamp whole‐cell recordings of the electroporated, spiny stellate neurons and extracellular recordings of the electroporated areas were performed in neocortical slices. Selective inhibitors were used to target mTOR activity and GluN2C‐mediated currents. Results: Neurons expressing the mutant protein displayed an excessive activation of GluN2C NMDAR‐mediated spontaneous excitatory postsynaptic currents. GluN2C‐dependent increase in spontaneous spiking activity was detected in the area of electroporated neurons in the mutant condition and was restricted to a critical time window between postnatal days P9 and P20. Significance: Somatic MTOR pathogenic variant recurrently found in FCD type II resulted in overactivation of GluN2C‐mediated neuronal NMDARs in neocortices of rat pups. The related and time‐restricted local hyperexcitability was sensitive to subunit GluN2C‐specific blockade. Our study suggests that GluN2C‐related pathomechanisms might be shared in common by mTOR‐related brain disorders. [ABSTRACT FROM AUTHOR]

Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that, in addition to electrical recording and stimulation, enables a more thorough investigation of neural circuit dynamics. We have designed a novel, flexible, implantable neural probe capable of controlled, localized chemical stimulation and electrophysiology recording. The neural probe was implemented using planar micromachining processes on Parylene C, a mechanically flexible, biocompatible substrate. The probe shank features two large microelectrodes (chemical sites) for drug loading and sixteen small microelectrodes for electrophysiology recording to monitor neuronal response to drug release. To reduce the impedance while keeping the size of the microelectrodes small, poly(3,4-ethylenedioxythiophene) (PEDOT) was electrochemically coated on recording microelectrodes. In addition, PEDOT doped with mesoporous sulfonated silica nanoparticles (SNPs) was used on chemical sites to achieve controlled, electrically-actuated drug loading and releasing. Different neurotransmitters, including glutamate (Glu) and gamma-aminobutyric acid (GABA), were incorporated into the SNPs and electrically triggered to release repeatedly. An in vitro experiment was conducted to quantify the stimulated release profile by applying a sinusoidal voltage (0.5 V, 2 Hz). The flexible neural probe was implanted in the barrel cortex of the wild-type Sprague Dawley rats. As expected, due to their excitatory and inhibitory effects, Glu and GABA release caused a significant increase and decrease in neural activity, respectively, which was recorded by the recording microelectrodes. This novel flexible neural probe technology, combining on-demand chemical release and high-resolution electrophysiology recording, is an important addition to the neuroscience toolset used to dissect neural circuitry and investigate neural network connectivity. [ABSTRACT FROM AUTHOR]

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders. [ABSTRACT FROM AUTHOR]

Brain-inspired neuromorphic computing has garnered significant attention for going beyond the constraint of von Neumann architecture. To emulate the human brain functions, various artificial synaptic devices have been proposed. Due to the high reliability and the CMOS compatibility, the synaptic transistors based on charge trapping (CT) mechanism have been considered to be one of the most promising candidates. However, most of the synaptic transistors based on CT mechanism were fabricated by costly vacuum-based techniques. In this report, based on a fully solution-driven strategy, the InZnO synaptic transistors, with Nd2O3 as the CT layer and ZrO2 as the dielectric layer, were integrated. The typical synaptic behaviors, including excitatory postsynaptic current, inhibitory postsynaptic current, memory enhancement, potentiation, and depression characteristics, were simulated by modulating presynaptic spikes. It is confirmed that the fabricated synaptic transistor shows low channel conductance and low energy consumption of 0.13 pJ per synaptic event. A recognition accuracy of 93.0% was achieved for the MNIST handwritten digital image dataset by an artificial neural network simulation. This study demonstrates the feasibility of solution-processed synaptic transistors, which exhibit significant potential for the neuromorphic applications. [ABSTRACT FROM AUTHOR]

Transspinal (or transcutaneous spinal cord) stimulation is a noninvasive, cost-effective, easily applied method with great potential as a therapeutic modality for recovering somatic and nonsomatic functions in upper motor neuron disorders. However, how transspinal stimulation affects motor neuron depolarization is poorly understood, limiting the development of effective transspinal stimulation protocols for rehabilitation. In this study, we characterized the responses of soleus α motor neurons to single-pulse transspinal stimulation using single-motor unit (SMU) discharges as a proxy given the 1:1 discharge activation between the motor neuron and the motor unit. Peristimulus time histogram, peristimulus frequencygram, and surface electromyography (sEMG) were used to characterize the postsynaptic potentials of soleus motor neurons. Transspinal stimulation produced short-latency excitatory postsynaptic potentials (EPSPs) followed by two distinct phases of inhibitory postsynaptic potentials (IPSPs) in most soleus motor neurons and only IPSPs in others. Transspinal stimulation generated double discharges at short interspike intervals in a few motor units. The short-latency EPSPs were likely mediated by muscle spindle group Ia and II afferents, and the IPSPs via excitation of group Ib afferents and recurrent collaterals of motor neurons leading to activation of diverse spinal inhibitory interneuronal circuits. Further studies are warranted to understand better how transspinal stimulation affects depolarization of α motor neurons over multiple spinal segments. This knowledge will be seminal for developing effective transspinal stimulation protocols in upper motor neuron lesions. NEW & NOTEWORTHY: Transspinal stimulation produces distinct actions on soleus motor neurons: an early short-latency excitation followed by two inhibitions or only inhibition and doublets. These results show how transspinal stimulation affects depolarization of soleus α motor neurons in healthy humans. [ABSTRACT FROM AUTHOR]

Both microvoids and helium (He) impurities are widely present in tungsten (W) plasma-facing materials (PFMs), where the interaction between microvoids and He atoms has led to the intriguing development of microvoids. In this paper, we comprehensively investigated the interaction between He atoms and trivacancy (V3), a fundamental microvoid in W-PFMs, at the level of tight-binding theory. Our study showed that He atoms can catalyze the decomposition of the original V3 or facilitate its transformation into another V3 variant. We propose that a He atom near the V3 defect induces significant changes in the distribution of d-electron charges within the W atoms lining the inner wall of the V3 defect, making the W atom nearest to this He atom cationic and the other W atoms anionic. The attractive interaction between them promotes the decomposition and deformation of V3. As electronic excitation increases, the ionization of W atoms on the V3 wall gradually intensifies, thereby enhancing the cationic characteristics of the W atoms closest to the He atom. This process also prompts other W atoms to shift from anions to cations, leading to a transition in the electrostatic interactions between them from attraction to repulsion. This transformation, driven by electronic excitation, plays a significant inhibitory role in the decomposition and deformation of V3. [ABSTRACT FROM AUTHOR]

A better understanding of the neural mechanisms regulating impaired satiety to palatable foods is essential to treat hyperphagia linked with obesity. The satiation hormone amylin signals centrally at multiple nuclei including the ventral tegmental area (VTA). VTA–to–medial prefrontal cortex (mPFC) projections encode food reward information to influence behaviors including impulsivity. We hypothesized that modulation of VTA-to-mPFC neurons underlies amylin-mediated decreases in palatable food-motivated behaviors. We used a variety of pharmacological, behavioral, genetic, and viral approaches (n = 4–16/experiment) to investigate the anatomical and functional circuitry of amylin-controlled VTA-to-mPFC signaling in rats. To first establish that VTA amylin receptor (calcitonin receptor) activation can modulate mPFC activity, we showed that intra-VTA amylin decreased food-evoked mPFC cFos. VTA amylin delivery also attenuated food-directed impulsive behavior, implicating VTA amylin signaling as a regulator of mPFC functions. Palatable food activates VTA dopamine and mPFC neurons. Accordingly, dopamine receptor agonism in the mPFC blocked the hypophagic effect of intra-VTA amylin, and VTA amylin injection reduced food-evoked phasic dopamine levels in the mPFC, supporting the idea that VTA calcitonin receptor activation decreases dopamine release in the mPFC. Surprisingly, calcitonin receptor expression was not found on VTA-to-mPFC projecting neurons but was instead found on GABAergic (gamma-aminobutyric acidergic) interneurons in the VTA that provide monosynaptic inputs to this pathway. Blocking intra-VTA GABA signaling, through GABA receptor antagonists and DREADD (designer receptor exclusively activated by designer drugs)–mediated GABAergic neuronal silencing, attenuated intra-VTA amylin-induced hypophagia. These results indicate that VTA amylin signaling stimulates GABA-mediated inhibition of dopaminergic projections to the mPFC to mitigate impulsive consumption of palatable foods. [ABSTRACT FROM AUTHOR]

Nervous system has distinct anisotropy and some intrinsic biophysical properties enable neurons present various firing modes in neural activities. In presence of realistic electromagnetic fields, non-uniform radiation activates these neurons with energy diversity. By using a feasible model, energy function is obtained to predict the growth of synaptic connections of these neurons. Distribution of average value of the Hamilton energy function vs. intensity of noisy disturbance can predict the occurrence of coherence resonance, which the neural activities show high regularity by applying noisy disturbance with moderate intensity. From physical viewpoint, the average energy value has similar role average power for the neuron. Non-uniform spatial disturbance is applied and energy is injected into the neural network, statistical synchronization factor is calculated to predict the network synchronization stability and wave propagation. The intensity for field coupling is adaptively controlled by energy diversity between adjacent neurons. Local energy balance will terminate further growth of the coupling intensity; otherwise, heterogeneity is formed in the network due to energy diversity. Furthermore, memristive channel current is introduced into the neuron model for perceiving the effect of electromagnetic induction and radiation, and a memristive neuron is obtained. The circuit implement of memristive circuit depends on the connection to a magnetic flux-controlled memristor into the mentioned neural circuit in an additive branch circuit. The connection and activation of this memristive neural network are controlled under external spatial electromagnetic radiation by capturing enough field energy. Continuous energy collection and exchange generate energy diversity and synaptic connection is created to regulate the synchronous firing patterns and energy balance. • A feasible memristive neuron is proposed and its physical property is clarified. • Average Hamilton energy is effective to predict coherence resonance under noisy disturbance. • Non-uniform radiation is applied on the neural network with adaptive coupling. • Energy level controls the growth of synaptic connections. [ABSTRACT FROM AUTHOR]

This study implements a highly uniform 3D vertically stack resistive random‐access memory (VRRAM) with a four‐layer contact hole structure. The fabrication process of a four‐layer VRRAM is demonstrated, and its physical and electrical properties are thoroughly examined. X‐ray photoelectron spectroscopy and transmission electron microscopy are employed to analyze the chemical distribution and physical structure of the VRRAM device. Multilevel capability, reliable endurance (>104 cycles), and retention (104 s) are successfully obtained. Synaptic memory plasticity, such as spike time‐dependent plasticity, spike rate‐dependent plasticity, excitatory post‐synaptic current, paired‐pulse facilitation, and long‐term potentiation and depression is presented. Finally, the vector‐matrix multiplication (VMM) operation is conducted on a 4 × 12 VRRAM array, according to the low resistance state ratio. It is ascertained that the accuracy drop, which can occur due to VMM error, can be limited to a decrease of less than 0.44% point. Utilizing the high‐density, multilevel, and biological characteristics of VRRAM, it is possible to implement high‐performance neuromorphic systems that require densely integrated synaptic devices. [ABSTRACT FROM AUTHOR]

Antiphase bursting related to the rhythmic motor behavior exhibits complex dynamics modulated by the inhibitory synaptic current (Isyn), especially in the presence of the hyperpolarization-activated cation current (Ih). In the present paper, the dynamics of antiphase bursting modulated by the Ih and Isyn is studied in three aspects with a theoretical model. Firstly, the Isyn and the slow Ih with strong strength are the identified to be the necessary conditions for the antiphase bursting. The dependence of the antiphase bursting on the two currents is different for low (escape mode) and high (release mode) threshold voltages (Vth) of the inhibitory synapse. Secondly, more detailed co-regulations of the two currents to induce opposite changes of the bursting period are obtained. For the escape mode, increase of the Ih induces elevated membrane potential of the silence inhibited by a strong Isyn and shortened silence duration to go beyond Vth, resulting in reduced bursting period. For the release mode, increase of the Ih induces elevated tough value of the former part of the burst modulated by a nearly zero Isyn and lengthen burst duration to fall below Vth, resulting in prolonged bursting period. Finally, the fast-slow dynamics of the antiphase bursting are acquired. Using one-and two-parameter bifurcations of the fast subsystem of a single neuron, the burst of the antiphase bursting is related to the stable limit cycle, and the silence modulated by a strong Isyn to the stable equilibrium to a certain extent. The Ih mainly modulates the dynamics within the burst and quiescent state. Furthermore, with the fast subsystem of the coupled neurons, the silence is associated with the unstable equilibrium point. The results present theoretical explanations to the changes in the bursting period and fast-slow dynamics of the antiphase bursting modulated by the Isyn and Ih, which is helpful for understanding the antiphase bursting and modulating rhythmic motor patterns. [ABSTRACT FROM AUTHOR]

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This document is an editorial published in the journal Frontiers in Neurology. It discusses advances in translational approaches to studying epileptic seizure disorders in animal models. The editorial highlights various research topics, including improving the translational value of animal models, understanding the genetic predisposition to epilepsy, investigating knockout and genetically modified rats/mice, exploring new genetic technologies, and identifying novel treatment options for therapy-resistant epilepsy. The authors present a collection of studies that aim to bridge the gap between animal data and clinical trials, with the goal of improving our understanding of the neurobiological etiology of seizures and related comorbidities. [Extracted from the article]

Postinhibitory excitation is a transient overshoot of a neuron's baseline firing rate following an inhibitory stimulus and can be observed in vivo in human motoneurons. However, the biophysical origin of this phenomenon is still unknown and both reflex pathways and intrinsic motoneuron properties have been proposed. We hypothesized that postinhibitory excitation in motoneurons can be facilitated by hyperpolarization-activated inward currents (h-currents). Using an electrical circuit model, we investigated how h-currents can modulate the postinhibitory response of motoneurons. Further, we analyzed the spike trains of human motor units from the tibialis anterior muscle during reciprocal inhibition. The simulations revealed that the activation of h-currents by an inhibitory postsynaptic potential can cause a short-term increase in a motoneuron's firing probability. This result suggests that the neuron can be excited by an inhibitory stimulus. In detail, the modulation of the firing probability depends on the time delay between the inhibitory stimulus and the previous action potential. Further, the postinhibitory excitation's strength correlates with the inhibitory stimulus's amplitude and is negatively correlated with the baseline firing rate as well as the level of input noise. Hallmarks of h-current activity, as identified from the modeling study, were found in 50% of the human motor units that showed postinhibitory excitation. This study suggests that h-currents can facilitate postinhibitory excitation and act as a modulatory system to increase motoneuron excitability after a strong inhibition. Author summary: Human movement is determined by the activity of specialized nerve cells, the motoneurons. Each motoneuron activates a specific set of muscle fibers. The functional unit consisting of a neuron and muscle fibers is called a motor unit. The activity of motoneurons can be observed noninvasively in living humans by recording the electrical activity of the motor units using the electromyogram. We studied the behavior of human motor units in an inhibitory reflex pathway and found an unexpected response pattern: a rebound-like excitation following the inhibition. This has occasionally been reported for human motor units, but its origin has never been systematically studied. In non-human cells of the neural system, earlier studies reported that a specific membrane protein, the so-called h-channel, can cause postinhibitory excitation. Our study uses a computational motoneuron model to investigate whether h-channels can cause postinhibitory excitation, as observed in the experimental recordings. Using the model, we developed a method to detect features of h-channel activity in human recordings. Because we found these features in half of the recorded motor units, we conclude that h-channels can facilitate postinhibitory excitation in human motoneurons. [ABSTRACT FROM AUTHOR]

Summary: In leaves of C4 plants, the reactions of photosynthesis become restricted between two compartments. Typically, this allows accumulation of C4 acids in mesophyll (M) cells and subsequent decarboxylation in the bundle sheath (BS). In C4 grasses, proliferation of plasmodesmata between these cell types is thought to increase cell‐to‐cell connectivity to allow efficient metabolite movement. However, it is not known whether C4 dicotyledons also show this enhanced plasmodesmal connectivity and so whether this is a general requirement for C4 photosynthesis is not clear. How M and BS cells in C4 leaves become highly connected is also not known.We investigated these questions using 3D‐ and 2D‐electron microscopy on the C4 dicotyledon Gynandropsis gynandra as well as phylogenetically close C3 relatives.The M–BS interface of C4G. gynandra showed higher plasmodesmal frequency compared with closely related C3 species. Formation of these plasmodesmata was induced by light. Pharmacological agents that perturbed photosynthesis reduced the number of plasmodesmata, but this inhibitory effect could be reversed by the provision of exogenous sucrose.We conclude that enhanced formation of plasmodesmata between M and BS cells is wired to the induction of photosynthesis in C4G. gynandra. [ABSTRACT FROM AUTHOR]

The role of serotonin 5-HT5A receptors in the modulation of miniature inhibitory synaptic activity was studied using intracellular recording of miniature glycinergic inhibitory postsynaptic potentials (glymIPSPs) in the lumbar motoneurons of the isolated spinal cord of the frog Rana ridibunda. In a medium containing TTx, CNQX, D-AP5, bicuculline, application of the serotonin receptor agonist 5-CT (10 µM) with high affinity for 5-HT5A led to a suppression of frequency by 86%, as well as the disappearance of high-amplitude glymIPSPs (200–500 µV) at preservation of rare potentials with an amplitude of about 100 µV. This effect indicates the possibility of pre- and postsynaptic action of 5-CT at such a concentration, not limited to its effect only on 5-HT5A receptors. The addition of methysergide, a blocker of 5-HT1,2 receptors, to the medium reduced the average frequency of glymIPSPs by 67%, the frequency of high-amplitude events by 5 times and their average amplitude by 20%, which may indicate the participation of 5-HT5A receptors in pre- and postsynaptic modulation in glymIPSPs of motoneurons. Application of 1 µM 5-CT led to a decrease in the frequency of glymIPSPs by 49% without a noticeable change in the amplitude of glymIPSPs, and the subsequent introduction of SB-699551, a selective antagonist of 5-HT5A receptors, into the solution increased the frequency of events by 41%, which confirms the involvement of 5-HT5A receptors in presynaptic modulation of glymIPSPs. Immunofluorescence study showed that supra- and intraspinal 5-HT+ ir neurons produce abundant branching in the lumbar region with the possibility of forming axosomatic contacts with labeled motoneurons and axodendritic contacts on the proximal and distal portions of their dendrites. It is also possible to form contacts in the perimedullary plexus, penetrated by the distal dendrites of motoneurons and astrocytic processes. This represents the structural basis for post-, pre- and extrasynaptic modulation of motoneuron activity by serotonin. The possibility of postsynaptic modulation of motoneuron activity through 5-HT5A receptors is confirmed by the point-like fluorescence of the 5-HT5ARlike+ signal on the dendrites and bodies of labeled motoneurons, which is present in the neuropil but absent in the perimedullary plexus. Double labeling with antibodies to the 5-HT5A receptor and the Ca2+-binding protein, parvalbumin, revealed 5-HT5ARlike+ localization in the myelin sheath of dorsal and ventromedial funiculi fibers. In preparations after long-term stimulation of the ventral roots through suction electrodes when labeling motor neurons with biocytin, a bright 5-HT5ARlike+ signal was detected in the myelin of motor axons, dorsal root fibers entering the brain in the region of the dorsal horn and individual fibers of the ventromedial funiculus. The participation of extrasynaptic 5-HT5A receptors in the functioning of feedback circuits of lumbar motoneuron activity, with the possible participation of glial elements in these circuits, is discussed. [ABSTRACT FROM AUTHOR]

• Cutaneous silent period (CSP) latency of single motor units is prolonged in severely affected ALS patients, whereas the duration of CSP remained similar to healthy controls. • Discharge rate estimation revealed longer CSP duration compared to probabilistic methods. • Severely and mildly affected ALS patients lose motor unit discharge rate vs. CSP duration inverse correlation. Recent evidence indicated that amyotrophic lateral sclerosis (ALS) also impairs spinal circuits, including those mediating cutaneous silent period (CSP). However, most studies utilised surface electromyography (sEMG), which needs more resolution to pinpoint changes at the single motoneuron level. We aimed to investigate CSP properties using single motor unit discharges in ALS. In mild and severe ALS patients and controls, CSP was recorded in the first dorsal interosseus and analysed using the discharge rate method, which accurately shows the inhibitory postsynaptic potentials (IPSPs) profile. Our findings confirmed that the CSP latency was prolonged only in severe ALS patients. Moreover, the CSP duration was similar in each group, but late-stage ALS patients tend to have a longer CSP duration. The discharge rate method revealed a significantly longer duration (up to 150 ms) than the duration detected using sEMG. Strikingly, the motoneuron discharge rate – IPSP duration inverse relationship is lost in ALS patients, indicating a possible impairment in the motoneuron integrative properties. Our data support previous findings of prolonged latency, presented input–output modifications of motoneurons, and revealed the entire course of the CSP, representing a much stronger inhibitory event than previously thought. Motoneuron integrative property modification assessed by CSP could be a new biomarker for ALS. [ABSTRACT FROM AUTHOR]

Clinical imaging studies have revealed that the hypothalamus is activated in migraine patients prior to the onset of and during headache and have also shown that the hypothalamus has increased functional connectivity with the spinal trigeminal nucleus. The dopaminergic system of the hypothalamus plays an important role, and the dopamine-rich A11 nucleus may play an important role in migraine pathogenesis. We used intraperitoneal injections of glyceryl trinitrate to establish a model of acute migraine attack and chronicity in mice, which was verified by photophobia experiments and von Frey experiments. We explored the A11 nucleus and its downstream pathway using immunohistochemical staining and neuronal tracing techniques. During acute migraine attack and chronification, c-fos expression in GABAergic neurons in the A11 nucleus was significantly increased, and inhibition of DA neurons was achieved by binding to GABA A-type receptors on the surface of dopaminergic neurons in the A11 nucleus. However, the expression of tyrosine hydroxylase and glutamic acid decarboxylase proteins in the A11 nucleus of the hypothalamus did not change significantly. Specific destruction of dopaminergic neurons in the A11 nucleus of mice resulted in severe nociceptive sensitization and photophobic behavior. The expression levels of the D1 dopamine receptor and D2 dopamine receptor in the caudal part of the spinal trigeminal nucleus candalis of the chronic migraine model were increased. Skin nociceptive sensitization of mice was slowed by activation of the D2 dopamine receptor in SP5C, and activation of the D1 dopamine receptor reversed this behavioral change. GABAergic neurons in the A11 nucleus were activated and exerted postsynaptic inhibitory effects, which led to a decrease in the amount of DA secreted by the A11 nucleus in the spinal trigeminal nucleus candalis. The reduced DA bound preferentially to the D2 dopamine receptor, thus exerting a defensive effect against headache. [ABSTRACT FROM AUTHOR]

• Pharmacological activation of 5-HT 6 receptors increases the fIPSP of the dorsal hippocampus. • Activation of 5-HT 6 receptor decreases the amplitude of the pyramidal cells' population spike. • Blockade of 5-HT 6 receptors decreases the fIPSP amplitude and increases the pyramidal cells' population spike. • Paired-pulse inhibition is modulated by 5-HT 6 receptors acting via local interneurons. • Pharmacological blockade of GAT1 decreases associative memory performance induced by 5-HT6 receptor antagonism. The blockade of 5-HT 6 receptors represents an experimental approach that might ameliorate the memory deficits associated with brain disorders, including Alzheimer's disease and schizophrenia. However, the synaptic mechanism by which 5-HT 6 receptors control the GABAergic and glutamatergic synaptic transmission is barely understood. In this study, we demonstrate that pharmacological manipulation of 5-HT 6 receptors with the specific agonist EMD 386088 (7.4 nM) or the antagonist SB-399885 (300 nM) modulates the field inhibitory postsynaptic potentials of the dorsal hippocampus and controls the strength of the population spike of pyramidal cells. Likewise, pharmacological modulation of 5-HT 6 controls the magnitude of paired-pulse inhibition, a phenomenon mediated by GABAergic interneurons acting via GABA A receptors of pyramidal cells. The effects of pharmacological manipulation of the 5-HT 6 receptor were limited to GABAergic transmission and did not affect the strength of field excitatory postsynaptic potentials mediated by the Schaffer collaterals axons. Lastly, in a modified version of the Pavlovian autoshaping task that requires the activation of the hippocampal formation, we demonstrated that the anti-amnesic effect induced by the blockade of the 5-HT 6 receptor is prevented when the GAT1 transporter is blocked, suggesting that modulation of GABAergic transmission is required for the anti-amnesic properties of 5-HT 6 receptor antagonists. [ABSTRACT FROM AUTHOR]

The article focuses on the physiology of excitable tissue, discussing topics such as the resting membrane potential (RMP), movement of ions, and the action potential (AP). It explains how excitable tissues rely on the proper functioning of ion channels and pumps to generate and propagate action potentials, crucial for muscle contraction, nerve conduction, and other physiological processes.

Photodetectors sensing the short‐wave infrared (SWIR) region have great potential due to their significant advantages in a variety of applications because SWIR light possesses both characteristics of visible light and infrared light. Among them, devices using photodetectors to mimic synaptic dynamics and functions have received a great deal of attention due to their capabilities to implement simplified neural systems. However, it is essential to develop synaptic devices that can operate fast with low energy consumption for more efficient implementation of neural systems. Here, a flexible InGaAs synaptic phototransistor with a fast operation speed of under 1 ms and low energy consumption in the atto joule level is developed to femto joule level which is superior to biological synapses (50 ms, 1–100 fJ). By using InGaAs which has high carrier mobility as a channel layer, weak light, and short optical pulse width, fast operation speed in the SWIR region with low energy consumption is obtained. Moreover, the devices demonstrate synaptic behaviors such as "excitatory post synaptic current", "paired‐pulse facilitation", "short term plasticity", "long term plasticity", and "learning‐experience behavior" as neuro‐synaptic applications. These results provide the possibilities for implementation of complex synaptic functions with fast speed and low power SWIR synaptic phototransistors. [ABSTRACT FROM AUTHOR]

Background: Seizures are associated with a decrease in γ-aminobutyric type A acid receptors (GABAaRs) on the neuronal surface, which may be regulated by enhanced internalization of GABAaRs. When interactions between GABAaR subunit α-1 (GABRA1) and postsynaptic scaffold proteins are weakened, the α1-containing GABAaRs leave the postsynaptic membrane and are internalized. Previous evidence suggested that neuroplastin (NPTN) promotes the localization of GABRA1 on the postsynaptic membrane. However, the association between NPTN and GABRA1 in seizures and its effect on the internalization of α1-containing GABAaRs on the neuronal surface has not been studied before. Methods: An in vitro seizure model was constructed using magnesium-free extracellular fluid, and an in vivo model of status epilepticus (SE) was constructed using pentylenetetrazole (PTZ). Additionally, in vitro and in vivo NPTN-overexpression models were constructed. Electrophysiological recordings and internalization assays were performed to evaluate the action potentials and miniature inhibitory postsynaptic currents of neurons, as well as the intracellular accumulation ratio of α1-containing GABAaRs in neurons. Western blot analysis was performed to detect the expression of GABRA1 and NPTN both in vitro and in vivo. Immunofluorescence co-localization analysis and co-immunoprecipitation were performed to evaluate the interaction between GABRA1 and NPTN. Results: The expression of GABRA1 was found to be decreased on the neuronal surface both in vivo and in vitro seizure models. In the in vitro seizure model, α1-containing GABAaRs showed increased internalization. NPTN expression was found to be positively correlated with GABRA1 expression on the neuronal surface both in vivo and in vitro seizure models. In addition, NPTN overexpression alleviated seizures and NPTN was shown to bind to GABRA1 to form protein complexes that can be disrupted during seizures in both in vivo and in vitro models. Furthermore, NPTN was found to inhibit the internalization of α1-containing GABAaRs in the in vitro seizure model. Conclusion: Our findings provide evidence that NPTN may exert antiepileptic effects by binding to GABRA1 to inhibit the internalization of α1-containing GABAaRs. [ABSTRACT FROM AUTHOR]

Experimental warming of an ombrotrophic bog in northern Minnesota has caused a rapid decline in the productivity and areal cover of Sphagnum mosses, affecting whole‐ecosystem carbon balance and biogeochemistry. Direct effects of elevated temperature and the attendant drying are most likely the primary cause of the effects on Sphagnum, but there may also be responses to the increased shading from shrubs, which increased with increasing temperature. To evaluate the independent effects of reduction in light availability and deposition of shrub litter on Sphagnum productivity, small plots with shrubs removed were laid out adjacent to the warming experiment on hummocks and hollows in three blocks and with five levels of shading. Four plots were covered with neutral density shade cloth to simulate shading from shrubs of 30%–90% reduction in light; one plot was left open. Growth of Sphagnum angustifolium/fallax and S. divinum declined linearly with increasing shade in hollows, but there was no response to shade on hummocks, where higher irradiance in the open plots may have been inhibitory. Shading caused etiolation of Sphagnum—they were thin and spindly under the deepest shade. A dense mat of shrub litter, corresponding to the amount of shrub litter produced in response to warming, did not inhibit Sphagnum growth or cause increases in potentially toxic base cations. CO2 exchange and chlorophyll‐a fluorescence of S. angustifolium/fallax from the 30% and 90% shade cloth plots were measured in the laboratory. Light response curves indicate that maximal light saturated photosynthesis was 42% greater for S. angustifolium/fallax grown under 30% shade cloth relative to plants grown under 90% shade cloth. The response of Sphagnum growth in response to increasing shade is consistent with the hypothesis that increased shade resulting from shrub expansion in response to experimental warming contributed to reduced Sphagnum growth. [ABSTRACT FROM AUTHOR]

Electrical synapses supported by gap junctions are known to form networks of electrically coupled neurons in many regions of the mammalian brain, where they play relevant functional roles. Yet, how electrical coupling supports sophisticated network operations and the contribution of the intrinsic electrophysiological properties of neurons to these operations remain incompletely understood. Here, a comparative analysis of electrically coupled mesencephalic trigeminal (MesV) neurons uncovered remarkable difference in the operation of these networks in highly related species. While spiking of MesV neurons might support the recruitment of coupled cells in rats, this rarely occurs in mice. Using whole-cell recordings, we determined that the higher efficacy in postsynaptic recruitment in rat's MesV neurons does not result from coupling strength of larger magnitude, but instead from the higher excitability of coupled neurons. Consistently, MesV neurons from rats present a lower rheobase, more hyperpolarized threshold, as well as a higher ability to generate repetitive discharges, in comparison to their counterparts from mice. This difference in neuronal excitability results from a significantly higher magnitude of the D-type K+ current (ID) in MesV neurons from mice, indicating that the magnitude of this current gates the recruitment of postsynapticcoupled neurons. Since MesV neurons are primary afferents critically involved in the organization of orofacial behaviors, activation of a coupled partner could support lateral excitation, which by amplifying sensory inputs may significantly contribute to information processing and the organization of motor outputs. [ABSTRACT FROM AUTHOR]

Cheddar cheese‐derived bioactive peptides are considered a potential component of functional foods. A positive impact of bioactive peptides on diet‐related chronic, non‐communicable diseases, like obesity, cardiovascular diseases, and diabetes, has been observed. Bioactive peptides possess multifunctional therapeutic potentials, including antimicrobial, immunomodulatory, antioxidant, enzyme inhibitory effects, anti‐thrombotic, and phyto‐pathological activities against various toxic compounds. Peptides can regulate human immune, gastrointestinal, hormonal, and neurological responses, which play an integral role in the deterrence and treatment of certain diseases like cancer, osteoporosis, hypertension, and other health disorders, as described in the present review. This review summarizes the categories of the Cheddar cheese‐derived bioactive peptides, their general characteristics, physiological functions, and possible applications in healthcare. [ABSTRACT FROM AUTHOR]

Memristors are a promising technology to surpass the limitations of the current silicon complementary metal-oxide-semiconductor architecture via the realization of neuromorphic computing. Here, we demonstrate intercalation-based non-volatile lithium niobite (Li1 – xNbO2) memristors for highly scalable, efficient, and dense neuromorphic circuitry. Volatile, semi-volatile, and non-volatile operation is achieved using a single material, where each operational mode provides a timescale that enables short-term, medium-term, and long-term memory in conjunction with computation-in-memory. The two-terminal non-volatile devices exhibit conductance changes of up to ∼2000% and have inherent non-binary operations proportional to flux linkage, allowing for analog neuromorphic functions mimicking synaptic weight updates. It is shown that Li1 – xNbO2 devices are highly scalable due to the intercalation-based mechanism, with non-volatile operation requiring a mere 150 mV for a 4 μm2 device, the lowest reported operating voltage for an inorganic non-volatile memristor. The programming voltage scales linearly with device size, projecting millivolt operation and attojoule energy consumption for nanoscale devices. [ABSTRACT FROM AUTHOR]

High-density cultured neuronal networks have been used to evaluate synchronized features of neuronal populations. Voltage-sensitive dye (VSD) imaging of a dissociated cultured neuronal network is a critical method for studying synchronized neuronal activity in single cells. However, the signals of VSD are generally too faint—that is, the signal-to-noise ratio (S/N) is too low—to detect neuronal activity. In our previous research, a silver (Ag) plasmonic chip enhanced the fluorescence intensity of VSD to detect spontaneous neural spikes on VSD imaging. However, no high-density network was cultivated on the Ag plasmonic chip, perhaps because of the chemical instability of the Ag surface. In this study, to overcome the instability of the chip, we used a chemically stable gold (Au) plasmonic dish, which was a plastic dish with a plasmonic chip pasted to the bottom, to observe neuronal activity in a high-density neuronal network. We expected that the S/N in real-time VSD imaging of the Au plasmonic chip would be improved compared to that of a conventional glass-bottomed dish, and we also expected to detect frequent neural spikes. The increase in the number of spikes when inhibitory neurotransmitter receptors were inhibited suggests that the spikes corresponded to neural activity. Therefore, real-time VSD imaging of an Au plasmonic dish was effective for measuring spontaneous network activity in a high-density neuronal network at the spatial resolution of a single cell. [ABSTRACT FROM AUTHOR]

Using light signals for computation and communication is a vital approach for advanced neuromorphic designs. In this study, an all‐optical‐controlled IGZO/ZrOx phototransistor is demonstrated to emulate synaptic functions via both positive and negative photoresponse arisen from the ionization of neutral oxygen vacancies (VO) and metalmetal bonding (MM) defects in IGZO at an illumination with visible light (405 and 520 nm) and near‐infrared light (750, 890, and 980 nm), respectively. With the coupling effect of photogenerated electrons and the charged MM++ defect scattering, the IGZO/ZrOx photosynaptic transistor not only shows broadband photosensing performance but also emulates the excitatory/inhibitory contrasting synaptic functions, such as learning‐ and regulating‐experience behavior of human brain, via applying 405 and 890 nm light pulses, respectively. The all‐optical‐controlled IGZO/ZrOx photosynaptic transistor therefore may convey optical information effectually for the streaming sensor processing in biologically inspired computer vision application. [ABSTRACT FROM AUTHOR]

Venom‐derived peptides targeting ion channels involved in pain are regarded as a promising alternative to current, and often ineffective, chronic pain treatments. Many peptide toxins are known to specifically and potently block established therapeutic targets, among which the voltage‐gated sodium and calcium channels are major contributors. Here, we report on the discovery and characterization of a novel spider toxin isolated from the crude venom of Pterinochilus murinus that shows inhibitory activity at both hNaV1.7 and hCaV3.2 channels, two therapeutic targets implicated in pain pathways. Bioassay‐guided HPLC fractionation revealed a 36‐amino acid peptide with three disulfide bridges named μ/ω‐theraphotoxin‐Pmu1a (Pmu1a). Following isolation and characterization, the toxin was chemically synthesized and its biological activity was further assessed using electrophysiology, revealing Pmu1a to be a toxin that potently blocks both hNaV1.7 and hCaV3. Nuclear magnetic resonance structure determination of Pmu1a shows an inhibitor cystine knot fold that is the characteristic of many spider peptides. Combined, these data show the potential of Pmu1a as a basis for the design of compounds with dual activity at the therapeutically relevant hCaV3.2 and hNaV1.7 voltage‐gated channels. [ABSTRACT FROM AUTHOR]

Circadian rhythms in behavior and physiology such as rest/activity and hormones are driven by an internal clock and persist in the absence of rhythmic environmental cues. However, the period and phase of the internal clock are entrained by the environmental light/dark cycle. Consequently, aberrant lighting conditions, which are increasing in modern society, have a strong impact on rhythmic body and brain functions. Mice were exposed to three different lighting conditions, 12 h light/12 h dark cycle (LD), constant darkness (DD), and constant light (LL), to study the effects of the light/dark cycle and aberrant lighting on the hippocampus, a critical structure for temporal and spatial memory formation and navigation. Locomotor activity and plasma corticosterone levels were analyzed as readouts for circadian rhythms. Spatial working memory via Y-maze, spine morphology of Golgi–Cox-stained hippocampi, and plasticity of excitatory synapses, measured by number and size of synaptopodin and GluR1-immunreactive clusters, were analyzed. Our results indicate that the light/dark cycle drives diurnal differences in synaptic plasticity in hippocampus. Moreover, spatial working memory, spine density, and size and number of synaptopodin and GluR1 clusters were reduced in LL, while corticosterone levels were increased. This indicates that acute constant light affects hippocampal function and synaptic plasticity. [ABSTRACT FROM AUTHOR]

Activity-dependent modulation of electrical transmission typically involves Ca2+ influx acting directly on gap junctions or initiating Ca2+-dependent pathways that in turn modulate coupling. We now describe short-term use-dependent facilitation of electrical transmission between bag cell neurons from the hermaphroditic snail, Aplysia californica, that is instead mediated by changes in postsynaptic responsiveness. Bag cell neurons secrete reproductive hormone during a synchronous afterdischarge of action potentials coordinated by electrical coupling. Here, recordings from pairs of coupled bag cell neurons in culture showed that nonjunctional currents influence electrical transmission in a dynamic manner. Under a dual whole cell voltageclamp, the junctional current was linear and largely voltage-independent, while in current-clamp, the coupling coefficient was similar regardless of the extent of presynaptic hyperpolarization. Moreover, a train stimulus of action potential-like waveforms, in a voltage-clamped presynaptic neuron, elicited electrotonic potentials, in a current-clamped postsynaptic neuron, that facilitated over time when delivered at a frequency approximating the afterdischarge. Junctional current remained constant over the train stimulus, as did postsynaptic voltage-gated Ca2+ current. However, postsynaptic voltage-gated K+ current underwent cumulative inactivation, suggesting that K+ current run-down facilitates the electrotonic potential by boosting the response to successive junctional currents. Accordingly, preventing run-down by blocking postsynaptic K+ channels occluded facilitation. Finally, stimulation of bursts in coupled pairs resulted in synchronous firing, where active neurons could recruit silent partners through short-term use-dependent facilitation. Thus, potentiation of electrical transmission may promote synchrony in bag cell neurons and, by extension, reproductive function. [ABSTRACT FROM AUTHOR]

Optoelectronic synapses integrating sensing–memory–processing functions have great advantages in neuromorphic computing for visual information processing and complex learning, recognition, and memory in an energy‐efficient manner. Herein, a light‐induced bidirectional response is demonstrated in the proposed WSe2/MoS2 junction field‐effect transistor (JFET) with an extra Ge back gate. The WSe2/MoS2 JFET exhibits high responsivity and detectivity owing to effective modulation by the top junction and back dielectric gates. The unique bidirectional photoresponse and interfacial state storage properties of the device result in significant synaptic excitatory effects under visible light stimulation and remarkable synaptic inhibitory effects under infrared illumination. Optical storage with visible light and optical erasure with infrared light can be achieved in the device based on its synaptic behavior. The conductance changes under different types of illumination can be used to mimic the weight update in a neural network for image recognition. A high accuracy exceeding 98% was achieved in handwritten digit recognition. This visible and infrared dual‐band phototransistor, which integrates image perception, memory, and recognition functionalities, provides a promising solution for self‐driving, surveillance, computer vision, and biomedical imaging applications. [ABSTRACT FROM AUTHOR]

The proper development and function of telencephalic GABAergic interneurons is critical for maintaining the excitation and inhibition (E/I) balance in cortical circuits. Glutamate contributes to cortical interneuron (CIN) development via N-methyl-d-aspartate receptors (NMDARs). NMDAR activation requires the binding of a co-agonist, either glycine or d-serine. d-serine (co-agonist at many mature forebrain synapses) is racemized by the neuronal enzyme serine racemase (SR) from l-serine. We utilized constitutive SR knockout (SR−/−) mice to investigate the effect of d-serine availability on the development of CINs and inhibitory synapses in the prelimbic cortex (PrL). We found that most immature Lhx6 + CINs expressed SR and the obligatory NMDAR subunit NR1. At embryonic day 15, SR−/− mice had an accumulation of GABA and increased mitotic proliferation in the ganglionic eminence and fewer Gad1 + (glutamic acid decarboxylase 67 kDa; GAD67) cells in the E18 neocortex. Lhx6 + cells develop into parvalbumin (PV+) and somatostatin (Sst+) CINs. In the PrL of postnatal day (PND) 16 SR−/− mice, there was a significant decrease in GAD67+ and PV+, but not SST + CIN density, which was associated with reduced inhibitory postsynaptic potentials in layer 2/3 pyramidal neurons. These results demonstrate that D-serine availability is essential for prenatal CIN development and postnatal cortical circuit maturation. [ABSTRACT FROM AUTHOR]

Epileptic seizures have spatial features related to the propagation of seizure waves. As the main characteristic of absence seizures, 2–4 Hz spike-wave discharges (SWDs) originate from the cortices and are maintained by the thalamus. In this study, we explore the onset and propagation effect of absence seizures based on a thalamocortical model. First, we develop a two-compartment model and consider the autapse of the thalamic reticular nucleus as a crucial parameter to investigate transition behaviors. Moreover, we present dynamical mechanisms through bifurcation analysis. Simulation results show that the absence seizures can be induced and advanced as the coupling strength increases. Second, we investigate excitatory and inhibitory coupling functions in a three-compartment model. Our research indicates that the excitatory coupling function can lead to SWDs when all the compartments are initially saturated. In the process of propagation, excitatory coupling also gives rise to SWDs in normal compartments, whereas inhibitory coupling plays a limited role. Finally, we reproduce the above results in a 10-compartment model and verify the robustness against the variation of the number of modules. This work may shed new light on the field of seizure propagation and provide potential dynamical mechanisms. [ABSTRACT FROM AUTHOR]

The amygdala, a brain center of emotional expression, contributes to appropriate behavior responses during acoustic communication. In support of that role, the basolateral amygdala (BLA) analyzes the meaning of vocalizations through the integration of multiple acoustic inputs with information from other senses and an animal’s internal state. The mechanisms underlying this integration are poorly understood. This study focuses on the integration of vocalization-related inputs to the BLA from auditory centers during this processing. We used intracellular recordings of BLA neurons in unanesthetized big brown bats that rely heavily on a complex vocal repertoire during social interactions. Postsynaptic and spiking responses of BLA neurons were recorded to three vocal sequences that are closely related to distinct behaviors (appeasement, low-level aggression, and high-level aggression) and have different emotional valence. Our novel findings are that most BLA neurons showed postsynaptic responses to one or more vocalizations (31 of 46) but that many fewer neurons showed spiking responses (8 of 46). The spiking responses were more selective than postsynaptic potential (PSP) responses. Furthermore, vocal stimuli associated with either positive or negative valence were similarly effective in eliciting excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), and spiking responses. This indicates that BLA neurons process both positive- and negative-valence vocal stimuli. The greater selectivity of spiking responses than PSP responses suggests an integrative role for processing within the BLA to enhance response specificity in acoustic communication. NEW & NOTEWORTHY The amygdala plays an important role in social communication by sound, but little is known about how it integrates diverse auditory inputs to form selective responses to social vocalizations. We show that BLA neurons receive inputs that are responsive to both negative- and positive-affect vocalizations but their spiking outputs are fewer and highly selective for vocalization type. Our work demonstrates that BLA neurons perform an integrative function in shaping appropriate behavioral responses to social vocalizations. [ABSTRACT FROM AUTHOR]

Current anti‐spastic medication significantly compromises motor recovery after spinal cord injury (SCI), indicating a critical need for alternative interventions. Because a shift in chloride homeostasis decreases spinal inhibition and contributes to hyperreflexia after SCI, we investigated the effect of bumetanide, an FDA‐approved sodium‐potassium‐chloride intruder (NKCC1) antagonist, on presynaptic and postsynaptic inhibition. We compared its effect with step‐training as it is known to improve spinal inhibition by restoring chloride homeostasis. In SCI rats, a prolonged bumetanide treatment increased postynaptic inhibition but not presynaptic inhibition of the plantar H‐reflex evoked by posterior biceps and semitendinosus (PBSt) group I afferents. By using in vivo intracellular recordings of motoneurons, we further show that a prolonged bumetanide increased postsynaptic inhibition by hyperpolarizing the reversal potential for inhibitory postsynaptic potentials (IPSPs) after SCI. However, in step‐trained SCI rats an acute delivery of bumetanide decreased presynaptic inhibition of the H‐reflex, but not postsynaptic inhibition. These results suggest that bumetanide might be a viable option to improve postsynaptic inhibition after SCI, but it also decreases the recovery of presynaptic inhibition with step‐training. We discuss whether the effects of bumetanide are mediated by NKCC1 or by off‐target effects. Key points: After spinal cord injury (SCI), chloride homeostasis is dysregulated over time in parallel with the decrease in presynaptic inhibition of Ia afferents and postsynaptic inhibition of motoneurons, and the development of spasticity.While step‐training counteracts these effects, it cannot always be implemented in the clinic because of comorbidities. An alternative intervention is to use pharmacological strategies to decrease spasticity without hindering the recovery of motor function with step‐training.Here we found that, after SCI, a prolonged bumetanide (an FDA‐approved antagonist of the sodium‐potassium‐chloride intruder, NKCC1) treatment increases postsynaptic inhibition of the H‐reflex, and it hyperpolarizes the reversal potential for inhibitory postsynaptic potentials in motoneurons.However, in step‐trained SCI, an acute delivery of bumetanide decreases presynaptic inhibition of the H‐reflex, but not postsynaptic inhibition.Our results suggest that bumetanide has the potential to decrease spastic symptoms related to a decrease in postsynaptic but not presynaptic inhibition after SCI. [ABSTRACT FROM AUTHOR]

[Display omitted] • Grin1 deletion in prospective parvalbumin interneurons reduces unitary GABA release. • Grin1 deletion in parvalbumin neurons impairs membrane properties and excitability. • No effect of Cav2.1 channel agonist on GABA release from Grin1 -deleted neurons. • Cav2.1-haploinsufficient parvalbumin neurons produce a similar GABA release deficit. • Grin1 deletion using parvalbumin promoter causes generally normal GABA release. N -methyl-D-aspartate receptor (NMDAR) hypofunction during brain development is likely to contribute to the manifestation of schizophrenia (SCZ) in young adulthood. The cellular targets of NMDAR hypofunction appear to be at least in part corticolimbic fast-spiking (FS) interneurons. However, functional alterations in parvalbumin (PV)-positive FS interneurons following NMDAR hypofunction are poorly understood. Paired patch-clamp recordings from murine cortical PV interneurons and pyramidal neurons revealed that genetic deletion of NMDAR subunit Grin1 in prospective PV interneurons before the second postnatal week impaired evoked- and synchronized-GABA release. Whereas intrinsic excitability and spiking characteristics were also disturbed by Grin1 deletion, neither restoring their excitability by K+ channel blockade nor increasing extracellular Ca2+ rescued the GABA release. GABA release was also insensitive to the Cav2.1 channel antagonist ω-agatoxin IVA. Heterozygous deletion of Cacna1a gene (encoding Cav2.1) in PV interneurons produced a similar GABA release phenotype as the Grin1 mutants. Treatment with the Cav2.1/2.2 channel agonist GV-58 augmented somatic Ca2+ currents and GABA release in Cacna1a -haploinsufficient PV interneurons, but failed to enhance GABA release in the Grin1 -deleted PV interneurons. Taken together, our results suggest that Grin1 deletion in prospective PV interneurons impairs proper maturation of membrane excitability and Cav2.1-recruited evoked GABA release. This may increase synaptic excitatory/inhibitory ratio in principal neurons, contributing to the emergence of SCZ-like phenotypes. [ABSTRACT FROM AUTHOR]

A signature of synaptic potentiation conductance has been observed in an α-Fe2O3/p-Si device fabricated using spin coating. The conductance of the device in dark conditions and illumination with a white light source was characterized as a function of the application of a periodic bias (voltage) with a triangular profile. The conductance of the device increases with the number of voltage cycles applied and plateaus to its maximum value of 0.70 μS under dark conditions and 12.00 μS under illumination, and this mimics the analog synaptic weight change with the action potential of a neuron. In the range of applied voltage from 0 V to 0.7 V, the conduction mechanism corresponds to trap-assisted tunneling (TAT) and in the range of 0.7–5 V it corresponds to the Poole–Frenkel emission (PFE). The conductance as a function of electrical pulses was fitted with a Hill function, which is a measure of cooperation in biological systems. In this case, it allows one to determine the turn-on threshold (K) of the device in terms of the number of voltage pulses, which are found to be 3 and 166 under dark and illumination conditions, respectively. The gradual conductance change and activation after a certain number of pulses perfectly mimics the synaptic potentiation of neurons. In addition, the threshold parameter extracted from the Hill equation fit, acting as the number of pulses for synaptic activation, is found to have programmability with the intensity of the light illumination. [ABSTRACT FROM AUTHOR]

Organic field‐effect transistor (OFET) memory devices are benefiting from their independent gate modulation advantages for hardware implementation of synaptic functionalities. However, the imitation of selective release of excitatory–inhibitory neurotransmitters in a unipolar synaptic OFET is challenging due to the unbalanced mobile carrier concentration. Here, a p‐type synaptic OFET memory with CsPbBr3 quantum dots (QDs) as nano‐floating gates (NFGs) is developed, which can emulate both the excitatory–inhibitory responses of the biological synapse and their reconfigurable nature. By controlling the offset difference between stimulus voltage and reading voltage, the concomitant and independently expressed excitatory and inhibitory responses are successfully implemented in a negative gate modulation manner, but without introducing an ambipolar semiconductor or additional optical terminal. This reconfigurable modulation is ascribed to the dynamic competition between external electric field and built‐in electric field assisted by charge trapping in shallow traps. The proposed gate voltage‐offset method can be generally adapted to other unipolar synaptic OFETs. These results provide insight into OFET memory devices for building neuromorphic hardware elements with tailorable synaptic plasticity. [ABSTRACT FROM AUTHOR]

The heat generation rate (HGR) of lithium-ion batteries is crucial for the design of a battery thermal management system. Machine learning algorithms can effectively solve nonlinear problems and have been implemented in the state estimation and life prediction of batteries; however, limited research has been conducted on determining the battery HGR through machine learning. In this study, we employ three common machine learning algorithms, i.e., artificial neural network (ANN), support vector machine (SVM), and Gaussian process regression (GPR), to predict the battery HGR based on our experimental data, along with cases of interpolation and extrapolation. The results indicated the following: (1) the prediction accuracies for the interpolation cases were better than those of extrapolation, and the R2 values of interpolation were greater than 0.96; (2) after the discharge voltage was added as an input parameter, the prediction of the ANN was barely affected, whereas the performance of the SVM and GPR were improved; and (3) the ANN exhibited the best performance among the three algorithms. Accurate results can be obtained by using a single hidden layer and no more than 15 neurons without the additional input, where the R2 values were in the range of 0.89–1.00. Therefore, the ANN is preferable for predicting the HGR of lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Introduction: The media’s recent focus on possible negative health outcomes following sports- related concussion has increased awareness as well as anxiety among parents and athletes. However, the literature on concussion outcomes is equivocal and limited by a variety of diagnostic approaches. Methods: The current study used a rigorous, open- access concussion identification method—the Ohio State University Traumatic Brain Injury Identification method (OSU TBI-ID) to identify concussion and periods of repeated, subclinical head trauma in 108 young adult athletes who also underwent a comprehensive protocol of cognitive tests, mood/anxiety questionnaires, and high-angular-resolution diffusion-weighted brain imaging to evaluate potential changes in white matter microstructure. Results: Analyses showed that athletes with a history of repetitive, subclinical impacts to the head performed slightly worse on a measure of inhibitory impulse control and had more anxiety symptoms compared to those who never sustained any type of head injury but were otherwise the same as athletes with no history of concussion. Importantly, there were no group differences in cerebral white matter as measured by tract- based spatial statistics (TBSS), nor were there any associations between OSU TBI-ID measures and whole-brain principal scalars and free-water corrected scalars. Discussion: Our results provide support for the hypothesis that it is not concussion per se, but repetitive head impacts that beget worse outcomes. [ABSTRACT FROM AUTHOR]

In the current scenario, scaling up the microbial production of nanoparticles with diverse biological applications is an emerging prospect for NPs' sustainable industry. Thus, this paper was conducted to develop a suitable applicative process for the myco-fabrication of cobalt-ferrite (CoFeNPs), selenium (SeNPs), and zinc oxide (ZnONPs) nanoparticles. A strain improvement program using gamma irradiation mutagenesis was applied to improve the NPs-producing ability of the fungal strains. The achieved yields of CoFeNPs, SeNPs, and ZnONPs were intensified by a 14.47, 7.85, and 22.25-fold increase from the initial yield following gamma irradiation and isolation of stable mutant strains. The myco-fabricated CoFeNPs, SeNPs, and ZnONPs were then exploited to study their wound healing, and anti-inflammatory. In addition, the acetylcholinesterase inhibition activities of the myco-fabricated NPs were evaluated and analyzed by molecular docking. The obtained results confirmed the promising wound healing, anti-inflammatory, and acetylcholinesterase inhibition potentials of the three types of NPs. Additionally, data from analyzing the interaction of NPs with acetylcholinesterase enzyme by molecular docking were in conformation with the experimental data. [ABSTRACT FROM AUTHOR]

Objectives: The aims of this study were to select heat-killed lactic acid bacteria (HKL) with antibiotic activity and investigate the efficacy of this bacteria in maintaining periodontal parameters in healthy participants. Materials and methods: An in vitro evaluation was conducted to assess the inhibitory efficacy of lactic acid bacteria against Porphyromonas gingivalis and Fusobacterium nucleatum subsp. nucleatum. The effects of HKL administration on various parameters (plaque control record, bleeding on probing, and probing pocket depth) were assessed in a randomized, placebo-controlled trial. Participants in the test and placebo groups (n = 32) consumed oral tablets containing placebo or HKL daily for 8 weeks. Oral bacteria in supraplaque and saliva were identified using 16S rRNA gene community profiling analysis. Results: Heat-killed Ligilactobacillus salivarius CP3365 significantly (p < 0.05) decreased the viability of oral bacteria and was selected for clinical trials. Administration of HKL CP3365 significantly (p < 0.05) inhibited increases in each parameter. No changes in the relative abundance of P. gingivalis or F. nucleatum subsp. nucleatum were detected by HKL CP3365, but the relative abundance of oral bacteria (genera Porphyromonas, Fusobacterium, and Haemophilus) was significantly (p < 0.05) decreased. Conclusion: HKL CP3365 effectively inhibited oral bacteria growth and was useful for maintaining periodontal health. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans is an important genetic model for neuroscience studies, used for analyses of how genes control connectivity, neuronal function, and behavior. To date, however, most studies of neuronal function in C. elegans are incapable of obtaining microscopy imaging with subcellular resolution and behavior analysis in the same set of animals. This constraint stems from the immobilization requirement for high-resolution imaging that is incompatible with behavioral analysis using conventional immobilization techniques. Here, we present a novel microfluidic device that uses surface acoustic waves (SAW) as a non-contact method to temporarily immobilize worms for a short period (30 seconds). We optimize the SAW based protocol for rapid switching between free-swimming and immobilized states, facilitating non-invasive analysis of swimming behavior as well as high-resolution synaptic imaging in the same animal. We find that the coupling of heat and acoustic pressure play a key role in the immobilization process. We introduce a proof-of-concept longitudinal study, illustrating that the device enables repeated imaging of fluorescently tagged synaptic receptors in command interneurons and analysis of swimming behavior in the same animals for three days. This longitudinal approach provides the first correlative analysis of synaptic glutamatergic receptors and swimming behavior in aging animals. We anticipate that this device will enable further longitudinal analysis of animal motility and subcellular morphological changes during development and aging in C. elegans. [ABSTRACT FROM AUTHOR]

• Carbachol hyperpolarized cholinergic neurons in ventrolateral periaqueductal gray. • Cholinergic hyperpolarization was mediated via M 2 receptors. • M 2 receptor activation induced GIRK currents by G-protein activation. • Intrinsic acetylcholine with neostigmine hyperpolarized cholinergic neurons. Acetylcholine plays a pivotal role in the regulation of functions such as pain and the sleep and wake cycle by modulating neural activities of the ventrolateral periaqueductal gray (vlPAG). Electrophysiological studies have shown that cholinergic effects are inconsistent among recorded neurons, particularly in the depolarization and hyperpolarization of the resting membrane potential (RMP). This discrepancy may be due to the neural subtype-dependent cholinergic modulation of the RMP. To examine this possibility, we performed whole-cell patch-clamp recordings from subtype-identified neurons using vesicular GABA transporter (VGAT)-Venus × ChAT-TdTomato rats and elucidated cellular mechanisms of cholinergic effects on the RMP. The application of carbachol hyperpolarized the RMP of cholinergic neurons in a dose-dependent manner but had much less of an effect on other neural subtypes, including GABAergic/glycinergic and glutamatergic neurons. Cholinergic hyperpolarization was accompanied by a decrease in input resistance. These cholinergic effects were blocked by AF-DX384 or gallamine and were mimicked by arecaidine but-2-ynyl ester tosylate, suggesting that the carbachol-induced hyperpolarization of the RMP in cholinergic neurons is mediated via M 2 receptors. Tertiapin suppressed the carbachol-induced G protein-activated inwardly rectifying potassium channel (GIRK) currents and hyperpolarization of the RMP in cholinergic neurons. Intracellular application of GDP-β-S blocked the carbachol-induced hyperpolarization of the RMP. Neostigmine slowly hyperpolarized the RMP in cholinergic neurons. These results suggest that neural firing of vlPAG cholinergic neurons is suppressed by GIRK currents induced via M 2 receptor activation, and this negative feedback regulation of cholinergic neuronal activities can be induced by acetylcholine, which is intrinsically released in the vlPAG. [ABSTRACT FROM AUTHOR]

Altered inhibition/excitation (I/E) balance contributes to various brain disorders. Dysfunctional GABAergic interneurons enhance or reduce inhibition, resulting in I/E imbalances. Differences in short-term plasticity between excitation and inhibition cause frequency-dependence of the I/E ratio, which can be altered by GABAergic dysfunction. However, it is unknown whether I/E imbalances can be rescued pharmacologically using a single dose when the imbalance magnitude is frequency-dependent. Loss of PGC-1α (peroxisome proliferator activated receptor γ coactivator 1α) causes transcriptional dysregulation in hippocampal GABAergic interneurons. PGC-1α-/- slices have enhanced baseline inhibition onto CA1 pyramidal cells, causing increased I/E ratio and impaired circuit function. High frequency stimulation reduces the I/E ratio and recovers circuit function in PGC-1α-/- slices. Here we tested if using a low dose of bicuculline that can restore baseline I/E ratio can also rescue the frequency-dependent I/E imbalances in these mice. Remarkably, bicuculline did not reduce the I/E ratio below that of wild type during high frequency stimulation. Interestingly, bicuculline enhanced the paired-pulse ratio (PPR) of disynaptic inhibition without changing the monosynaptic inhibition PPR, suggesting that bicuculline modifies interneuron recruitment and not GABA release. Bicuculline improved CA1 output in PGC-1α-/- slices, enhancing EPSP-spike coupling to wild type levels at high and low frequencies. Our results show that it is possible to rescue frequency-dependent I/E imbalances in an animal model of transcriptional dysregulation with a single treatment. • Loss of PGC-1a causes a frequency-dependent increase in I/E ratio in hippocampus. • A low dose of bicuculline restores the I/E ratio in PGC-1α−/− slices. • Bicuculline normalizes the I/E ratio at both short and long paired-pulse intervals. • This is through an effect on the paired-pulse ratio of disynaptic inhibition. • Restoration of CA1 circuit function in PGC-1α−/− slices occurs with bicuculline. [ABSTRACT FROM AUTHOR]

As a new generation of core components for neuromorphic computing, optoelectronic synaptic devices have the advantages of high bandwidth and less energy consumption. They can combine the functions of visual sensing, signal processing, and memory in one device. Herein, an all‐solid‐state optoelectronic synaptic transistor using indium gallium zinc oxide (IGZO) as the channel and lanthanum fluoride (LaF3) as the gate dielectric is designed and fabricated. Its synaptic plasticity induced by electric and optical stimuli is investigated. LaF3 is a solid superionic conductor with plenty of mobile fluoride ions, which can be used to achieve a high on/off ratio of more than 105 and a low subthreshold swing less than 150 mV dec−1 in this novel synaptic transistor. Due to the ion‐trapping effect at the interface, synaptic plasticity can be achieved upon electrical stimulation. Synaptic plasticity by light pulse stimuli can also be accomplished with the assistance of the persistent photoconductivity effect in IGZO channel. Furthermore, it is found that the synaptic plasticity induced by light stimuli can be modulated by gate voltage. These results provide a new way to control synaptic function and extend the function of optoelectronic synaptic devices. [ABSTRACT FROM AUTHOR]

Neurons in central nervous systems receive multiple synaptic inputs andtransform them into a largely standardized output to their target cells—the actionpotential. A simplified model posits that synaptic signals are integrated by linearsummation and passive propagation towards the axon initial segment, where thethreshold for spike generation is either crossed or not. However, multiple lines ofresearch during past decades have shown that signal integration in individualneurons is much more complex, with important functional consequences at thecellular, network, and behavioral-cognitive level. The interplay between concomitantexcitatory and inhibitory postsynaptic potentials depends strongly on the relativetiming and localization of the respective synapses. In addition, dendrites containmultiple voltage-dependent conductances, which allow scaling of postsynapticpotentials, non-linear input processing, and compartmentalization of signals.Together, these features enable a rich variety of single-neuron computations,including non-linear operations and synaptic plasticity. Hence, we have to reviseover-simplified messages from textbooks and use simplified computational models likeintegrate-and-fire neurons with some caution. This concept article summarizes themost important mechanisms of dendritic integration and highlights some recentdevelopments in the field. [ABSTRACT FROM AUTHOR]

The article reports tonic immobility and how it is associated with brain activity including suppression of movement and motor reflexes. It describes how changes in the environment provoke defensive behavioral states. It shows that cerebellar regulation of a neuropeptide-rich prepontine structure governs a defensive behavior triggered by an environmental threat.

Here in, a chitosan-based nanoformulation of P.acaulis was evaluated for its antibacterial and antibiofilm inhibitory activities against some known food-borne bacteria. The FTIR, FE-SEM, DLS and zeta-potential analysis were performed for confirming loading process, morphological appearance, hydrodynamic diameter and surface charge of the nanoparticles respectively. The results confirmed that, the nanoparticles had semi-spherical shape with the mean hydrodynamic diameter and surface charge of 89.8 ± 5.8 nm and 10.78 ± 2.7 mv respectively. Furthermore, the FTIR analysis approved that the nanoparticles were successfully loaded with ethyl acetate fraction from P.acaulis. The antibacterial and biofilm inhibitory activities of the nanoformulated fraction were significantly increased against the tested Gram positive strains than free sample. The results also confirmed that the fraction release from the nanoparticles follows a sustained manner release after 30 h in a logarithmic pattern. Based on the obtained results, chitosan based nanoformulation of P. acaulis can be considered for more evaluations to serve as an alternative natural antibiotic. [ABSTRACT FROM AUTHOR]

In this work, a compact model of the diffusive memristor is proposed from the perspective of the transition of electronic transmission mechanisms induced by the dynamics of the filament. First, a new physical model is established based on tunneling mechanisms that are used to fit the experimental data, and the results indicate that it is versatile enough for various diffusive memristors. In addition, the threshold voltage (V th) of the diffusive memristor negatively correlates with the ratio of ionic migration and the diffusion coefficient (u i /Ds), and the hold voltage (V h) positively correlates with the ratio of ionic diffusion and the migration coefficient (Ds/u i), which is useful for the selection of materials to achieve target electrical properties. Furthermore, the different parameters that influence the simulated switching curve are explored. The results indicate that the desired electrical characteristics can be obtained by adjusting these parameters. A compact electrical module model is then built and tested in LTspice to carry out bio-neuron and bio-synaptic performances completely. These simulations demonstrate that the model is reliable for exploring diffusive memristor applications. [ABSTRACT FROM AUTHOR]