Neuronal Electrical Activity Research Articles

N-acetylcysteine attenuates accumbal core neuronal activity in response to morphine in the reinstatement of morphine CPP in morphine extinguished rats

Numerous studies have suggested that N-acetylcysteine (NAC), has the potential to suppress drug craving in people with substance use disorder and reduce drug-seeking behaviors in animals. The nucleus accumbens (NAc) plays a crucial role in the brain's reward system, with the nucleus accumbens core (NAcore) specifically implicated in compulsive drug seeking and relapse. In this study, we aimed to explore the impact of subchronic NAC administration during the extinction period and acute NAC administration on the electrical activity of NAcore neurons in response to a priming dose of morphine in rats subjected to extinction from morphine-induced place preference (CPP).We conducted single-unit recordings in anesthetized rats on the reinstatement day, following the establishment of morphine-induced conditioned place preference (7 mg/kg, s.c., 3 days), and subsequent drug-free extinction. In the subchronically NAC-treated groups, rats received daily injections of either NAC (50 mg/kg; i.p.) or saline during the extinction period. On the reinstatement day, we recorded the spontaneous activity of NAcore neurons for 15 min, administered a priming dose of morphine, and continued recording for an additional 45 min. While morphine excited most recorded neurons in saline-treated rats, it failed to alter firing rates in NAC-treated rats that had received NAC during the extinction period. For acutely NAC-treated animals, we recorded the baseline activity of NAcore neurons for 10 min before administering a single injection of either NAC (50 mg/kg; i.p.) or saline in rats with no treatment during the extinction. Following 30 min of recording and a priming dose of morphine (1 mg/kg, s.c.), the recording continued for an additional 30 min. The firing activity of NAcore neurons did not show significant changes after morphine or NAC injection. In conclusion, our findings emphasize that daily NAC administration during the extinction period significantly attenuates the morphine-induced increase in firing rates of NAcore neurons during the reinstatement of morphine CPP. However, acute NAC injection does not produce the same effect. These results suggest that modulating glutamate transmission through daily NAC during extinction may effectively inhibit the morphine place preference following the excitatory effects of morphine on NAcore neurons.

Systemic Glucose Regulation by a Hindbrain Inhibitory Circuit in a Mouse Model of Type 1 Diabetes

Introduction: Previous work showed that increasing the electrical activity of inhibitory neurons in the dorsal vagal complex (DVC) is sufficient to increase whole-body glucose concentration in normoglycemic mice. Here we tested the hypothesis that deactivating GABAergic neurons in the dorsal hindbrain of hyperglycemic mice decreases synaptic inhibition of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) and reduces systemic glucose levels. Methods: Chemogenetic activation or inactivation of GABAergic neurons in the nucleus tractus solitarius (NTS) was used to assess effects of modulating parasympathetic output on blood glucose concentration in normoglycemic and hyperglycemic mice. Patch-clamp electrophysiology in vitro was used to assess cellular effects of chemogenetic manipulation of NTS GABA neurons. Results: Chemogenetic activation of GABAergic NTS neurons in normoglycemic mice increased their action potential firing, resulting in increased inhibitory synaptic input to DMV motor neurons and elevated blood glucose concentration. Deactivation of GABAergic DVC neurons in normoglycemic mice altered their electrical activity but did not alter systemic glucose levels. Conversely, stimulation of GABAergic DVC neurons in mice that were hyperglycemic subsequent to treatment with streptozotocin changed their electrical activity but did not alter whole-body glucose concentration, while deactivation of this inhibitory circuit significantly decreased circulating glucose concentration. Peripheral administration of a brain impermeant muscarinic acetylcholine receptor antagonist abolished these effects. Conclusion: Disinhibiting vagal motor neurons decreases hyperglycemia in a mouse model of type 1 diabetes. This inhibitory brainstem circuit emerges as a key parasympathetic regulator of whole-body glucose homeostasis that undergoes functional plasticity in hyperglycemic conditions.

Desflurane improves electrical activity of neurons and alleviates oxygen-glucose deprivation-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Several volatile anesthetics have presented neuroprotective functions in ischemic injury. This study investigates the effect of desflurane (Des) on neurons following oxygen-glucose deprivation (OGD) challenge and exploresthe underpinning mechanism. Mouse neurons HT22 were subjected to OGD, which significantly reduced cell viability, increased lactate dehydrogenase release, and promoted cell apoptosis. In addition, the OGD condition increased oxidative stress in HT22 cells, as manifested by increased ROS and MDA contents, decreased SOD activity and GSH/GSSG ratio, and reduced nuclear protein level of Nrf2. Notably, the oxidative stress and neuronal apoptosis were substantially blocked by Des treatment. Bioinformatics suggested potassium voltage-gated channel subfamily A member 1 (Kcna1) as a target of Des. Indeed, the Kcna1 expression in HT22 cells was decreased by OGD but restored by Des treatment. Artificial knockdown of Kcna1 negated the neuroprotective effects of Des. By upregulating Kcna1, Des activated the Kv1.1 channel, therefore enhancing K+ currents and inducing neuronal repolarization. Pharmacological inhibition of the Kv1.1 channel reversed the protective effects of Des against OGD-induced injury. Collectively, this study demonstrates that Des improves electrical activity of neurons and alleviates OGD-induced neuronal injury by activating the Kcna1-dependent Kv1.1 channel.

Dynamic behaviors analysis of fraction-order neural network under memristive electromagnetic induction

The dynamic behaviors of coupled neurons with different mathematical representations have received more and more attention in recent years. The coupling among heterogeneous neurons can show richer dynamic phenomena, which is of great significance in understanding the function of the human brain. In this paper, we present a fraction-order heterogeneous network with three neurons, which is built by coupling an FN neuron with two HR neurons. Complex electromagnetic surroundings have meaningful physical influence on the electrical activities of neurons. To imitate the effects of electromagnetic induction on the three-neuron heterogeneous network, we introduce a fraction-order locally active memristor in the neural network. The characteristics of this memristor are carefully analyzed by pinched hysteresis loops and its locally active characteristic is proved by the power-off plot and the DC <i>v-i</i> plot. Then, the parameter-dependent dynamic activities are investigated numerically by using several dynamical analysis methods, such as the phase diagrams, bifurcation diagrams, Lyapunov exponent spectra, and attraction basins. In addition, the network also reveals rich dynamic behaviors, including coexisting activities, anti-monotonicity phenomena, transient chaos and firing patterns, providing support for further investigating the firing patterns of the human brain. In particular, complex dynamics, including coexisting attractors, anti-monotonicity, and firing patterns, can be influenced by the order and strength of electrical synaptic coupling and electromagnetic induction. The control of the bistable state can be realized through the time feedback control method, so that the bistable state can be transformed into an ideal monostable state. The study of the fraction-order memristive neural network may expand the field of view for understanding the collective behaviors of neurons. Finally, based on the ARM platform, we give a digital implementation of the fraction-order memristive neural network, which can verify the consistency with the numerical simulation results. In the future, we will explore more interesting memristive neural networks and study different types of methods to control the firing behaviors of the networks.

Postweaning Social Isolation Alters Puberty Onset by Suppressing Electrical Activity of Arcuate Kisspeptin Neurons

Introduction: Postweaning social isolation (PWSI) in rodents is an advanced psychosocial stress model in early life. Some psychosocial stress, such as restrain and isolation, disrupts reproductive physiology in young and adult periods. Mechanisms of early-life stress effects on central regulation of reproduction need to be elucidated. We have investigated the effects of PWSI on function of arcuate kisspeptin (ARCKISS1) neurons by using electrophysiological techniques combining with monitoring of puberty onset and estrous cycle in male and female Kiss1-Cre mice. Methods: Female mice were monitored for puberty onset with vaginal opening examination during social isolation. After isolation, the estrous cycle of female mice was monitored with vaginal cytology. Anxiety-like behavior of mice was determined by an elevated plus maze test. Effects of PWSI on electrophysiology of ARCKISS1 neurons were investigated by the patch clamp method after intracranial injection of AAV-GFP virus into arcuate nucleus of Kiss1-Cre mice after the isolation period. Results: We found that both male and female isolated mice showed anxiety-like behavior. PWSI caused delay in vaginal opening and extension in estrous cycle length. Spontaneous-firing rates of ARCKISS1 neurons were significantly lower in the isolated male and female mice. The peak amplitude of inhibitory postsynaptic currents to ARCKISS1 neurons was higher in the isolated mice, while frequency of excitatory postsynaptic currents was higher in group-housed mice. Conclusion: These findings demonstrate that PWSI alters pre- and postpubertal reproductive physiology through metabolic and electrophysiological pathways.

Fractal Neurodynamics.

The neuronal ongoing electrical activity in the brain network, the neurodynamics, reflects the structure and functionality of generating neuronal pools. The activity of neurons due to their excitatory and inhibitory projections is associated with specific brain functions. Here, the purpose was to investigate if the local ongoing electrical activity exhibits its characteristic spectral and fractal features in wakefulness and sleep across and within subjects. Moreover, we aimed to show that measures typical of complex systems catch physiological features missed by linear spectral analyses. For this study, we concentrated on the evaluation of the power spectral density (PSD) and Higuchi fractal dimension (HFD) measures. Relevant clinical impact of the specific features of neurodynamics identification stands primarily in the potential of classifying cortical parcels according to their neurodynamics as well as enhancing the effectiveness of neuromodulation interventions to cure symptoms secondary to neuronal activity unbalances.

Molecular Targets of Cannabidiol warn against its consumption during pregnancy

People use cannabidiol (CBD), the primary non-psychoactive cannabinoid of cannabis, as a treatment for symptoms that are commonly associated with pregnancy including nausea, pain, and anxiety. Many people believe CBD is safe to take during pregnancy. However, CBD crosses the placenta and affects the activity of protein targets that are expressed in the fetal brain. Cannabidiol alters the activity of ion channels including voltage- gated sodium, potassium, and calcium channels that control the electrical activity of neurons. Abnormal electrical activity could disrupt brain function via changes in axon growth and synapse structure and function. Furthermore, CBD alters the activity of G- protein coupled receptors that are expressed in the fetal brain and are important for axon growth and guidance suggesting that fetal exposure could prevent axons from reaching their correct targets. Indeed, cannabidiol exposure reduces axon growth in vitro and in vivo. This raises the possibility that CBD consumption during pregnancy could disrupt fetal brain development. Recent studies show that oral cannabidiol consumption during pregnancy alters the excitability of the pyramidal neurons of the prefrontal cortex and affects postnatal cognitive function in mouse offspring. Furthermore, fetal CBD exposure increases thermal pain sensitivity in offspring. Gestational cannabidiol exposure affects compulsivity and memory in a different rodent model. Here, we discuss how CBD affects various ion channels and G-protein coupled receptors, the roles of these proteins in neurodevelopment, and evidence that CBD affects brain development.

Clinical Sensitivity of Fractal Neurodynamics.

Among the significant advances in the understanding of the organization of the neuronal networks that coordinate the body and brain, their complex nature is increasingly important, resulting from the interaction between the very large number of constituents strongly organized hierarchically and at the same time with "self-emerging." This awareness drives us to identify the measures that best quantify the "complexity" that accompanies the continuous evolutionary dynamics of the brain. In this chapter, after an introductory section (Sect. 15.1), we examine how the Higuchi fractal dimension is able to perceive physiological processes (15.2), neurological (15.3) and psychiatric (15.4) disorders, and neuromodulation effects (15.5), giving a mention of other methods of measuring neuronal electrical activity in addition to electroencephalography, such as magnetoencephalography and functional magnetic resonance. Conscious that further progress will support a deeper understanding of the temporal course of neuronal activity because of continuous interaction with the environment, we conclude confident that the fractal dimension has begun to uncover important features of the physiology of brain activity and its alterations.

Dynamics, synchronization and traveling wave patterns of flux coupled network of Chay neurons

Studies in the literature have demonstrated the significance of the synchronization of neuronal electrical activity for signal transmission and information encoding. In light of this importance, we investigate the synchronization of the Chay neuron model using both theoretical analysis and numerical simulations. The Chay model is chosen for its comprehensive understanding of neuronal behavior and computational efficiency. Additionally, we explore the impact of electromagnetic induction, leading to the magnetic flux Chay neuron model. The single neuron model exhibits rich and complex dynamics for various parameter choices. We explore the bifurcation structure of the model through bifurcation diagrams and Lyapunov exponents. Subsequently, we extend our study to two coupled magnetic flux Chay neurons, identifying mode locking and structures reminiscent of Arnold’s tongue. We evaluate the stability of the synchronized manifold using Lyapunov theory and confirm our findings through simulations. Expanding our study to networks of diffusively coupled flux Chay neurons, we observe coherent, incoherent, and imperfect chimera patterns. Our investigation of three network types highlights the impact of network topology on the emergent dynamics of the Chay neuron network. Regular networks exhibit diverse patterns, small-world networks demonstrate a critical transition to coherence, and random networks showcase synchronization at specific coupling strengths. These findings significantly contribute to our understanding of the synchronization patterns exhibited by the magnetic flux Chay neuron. To assess the synchronization stability of the Chay neuron network, we employ master stability function analysis.

Investigation of the functioning of a neurohybrid system based on the FitzHugh–Nagumo radio generator and mouse hippocampal neurons

Currently, in the treatment of neurodegenerative diseases that are difficult to respond to drug therapy, electrical stimulation of the brain is performed through invasive intervention in damaged structures of the nervous tissue. The development and development of invasive technologies of closed-loop neural interfaces have made it possible to achieve great success in restoring neural connections, since they have finer and more precise stimulation settings that respond to changes in the physiological state, which is important in the process of restoring the functions of the nervous tissue. Advances in these areas open up prospects for the treatment of a wide range of diseases of the motor system and neurodegenerative diseases of the brain. In this study, a neurohybrid closed system was used, consisting of a FitzHugh-Nagumo radio generator and live surviving slices of the mouse brain hippocampus. For the preparation of surviving slices of the hippocampus, sexually mature males aged 2-3 months of the C57BL/6 mouse line were used. For the preparation and incubation of slices of the hippocampus, a solution of artificial cerebrospinal fluid (ACSF) was used, composition in (mM): 126 NaCl; 3.5 KCl; 1.2 KH2PO4; 26 NaHCO3; 1.3 MgCl * 6H2O; 2 CaCl2 * 6H2O; 10 D-glucose at constant carbogen saturation (95% O2 and 5% CO2). Registration of the electrical activity of brain neurons was carried out using optical and electrophysiological methods. In experiments on pairing a neuron-like FitzHugh-Nagumo generator and biological nerve cells in a closed circuit, an effect was obtained when the activity of brain nerve cells switched the generator to a self-oscillating mode. The evoked oscillations in the neuron-like generator provided an effective stimulus for the activation of nerve fibers in the perforant pathway of the hippocampus. As a result, it was possible to fix a decrease in the frequency of the generator impulses, which was provoked by the responses of living neurons to the incoming stimulus from the neuron-like generator. These results show the ability of live neural networks to control an artificial signal by adjusting its parameters by changing their own activity and confirm the efficiency of using closed loop systems when combining live and artificial neurons. The present study requires further experiments to create more physiological conditions for the functioning of the proposed neurohybrid system. In addition, this neurohybrid system will be improved and have adaptive properties through the use of memristive devices. Advances in this direction will help solve the urgent problem of restoring lost brain functions at the cellular and network levels.

Characteristics of murine phenotypes with signs of epilepsy obtained through ENU mutagenesis

Epilepsy is a chronic neurological disorder marked by recurring seizures and associated dysfunctions of motor, sensory, autonomic, and mental functions resulting from excessive electrical activity of neurons. Identification and characterization of the mutations that cause this pathology are essential for understanding the mechanisms that control epileptogenesis. The aim of the study is to characterize the S8-3 mutant mice strain, which shows induced epileptiform activity in response to audiogenic stimulation. Mutant strains of mice were acquired through induced chemical mutagenesis using N-ethyl-N-nitrosourea (ENU). Twenty-nine male mice were administered three rounds of ENU injections at a dose of 90 mg/kg during the study. On day 21 after birth (P21), identification and selection of mouse mutants with an elevated inclination towards epileptic seizures were conducted using the Krushinsky scale, which considered the intensity of audiogenic seizures. Strains with a recessive mutation were created by selecting animals that exhibited the aberrant phenotype for the second time. The abnormal phenotype was confirmed in the G5 generation, and basic behavioral phenotyping was performed to characterize the resulting epileptic lines. Correct grammar, spelling, and punctuation. This included assessing memory, learning ability, motor reactions, and emotional status. In vitro experiments assessed spontaneous calcium activity with primary neuronal cultures of the cerebral cortex isolated from newborn mice. The Ca2+ indicator used was Oregon Green 488 BAPTA-1 AM. Upon screening 60 strains of mice for sensitivity to audiogenic stimulation, 12 strains exhibiting epileptiform activity were observed. Subsequently, the S8-3 group was selected for further research, as its offspring (G3) showed a higher frequency of the aberrant phenotype in comparison to the other groups. Results from behavioral studies comparing S5-1 mice to the control hybrid animal group displayed a higher intensity of the acoustic startle response. The open field tests revealed that the motor activity of S8-3 strain mice was higher than that of the control group, based on the average distance traveled, and their anxiety level was lower, as indicated by fewer rears, urinary points, and boluses. When assessing cognitive functions through the CPAR test, mutant individuals exhibited high learning ability. In vitro experiments showed an increase in the frequency of spontaneous calcium events in primary cell cultures of the cerebral cortex isolated from S8-3 mice.

Alzheimer’s disease risk gene BIN1 modulates neural network activity through the regulation of L‐type calcium channel expression in human induced neurons

AbstractBackgroundBridging Integrator 1 (BIN1) is the second most important Alzheimer’s disease (AD) risk gene after APOE, but its physiological roles and contribution to brain pathology are largely elusive. In this work, we tackled the short‐ and long‐term effects of BIN1 deletion in human induced neurons (hiNs).MethodWe generated isogenic BIN1 WT, KO and HET human induced pluripotent stem cells (hiPSCs), which were differentiated into hiNs grown in 2D and 3D (cerebral organoids) cultures. We also developed a novel protocol for the generation of highly pure glutamatergic neuron cultures, allowing the study of cell‐autonomous roles of BIN1. Using these three different systems, we probed neuronal electrical activity using MEA electrophysiology and gene expression alterations in individual cell types using snRNA‐seq.ResultWe show that BIN1 depletion leads to specific transcriptional alterations in glutamatergic neurons involving mainly genes associated with calcium homeostasis, ion transport and synapse function. We also show that BIN1 regulates calcium transients and neuronal electrical activity through interaction with the L‐type voltage‐gated calcium channel Cav1.2 and regulation of activity‐dependent internalization of this channel. Treatment with the Cav1.2 antagonist nifedipine partly rescues neuronal electrical and gene expression alterations in BIN1 knockout hiNs.ConclusionOur results indicate that BIN1 loss‐of‐function impairs calcium homeostasis at least in glutamatergic neurons, potentially contributing to the transcriptional changes and neural network dysfunctions observed in AD.

Discovery of Novel Ophthalmic Imaging Biomarkers for Neurodegenerative Disease

AbstractBackgroundThe retina is increasingly investigated as a site of Alzheimer’s Disease (AD) manifestation, with amyloid β (Aβ) plaques being found in the retina of AD and mild cognitively impaired (MCI) patients, however functional changes in the retina are poorly understood. Retinal imaging techniques can be utilized for neurodegenerative biomarkers, since the retina is the only CNS organ available for noninvasive tracking.MethodRetinal imaging techniques were using to compare the retina of wild‐type (WT) or AD transgenic mice containing the APP: Swedish and Indiana mutation expressed under the prion promoter (TgCRND8) at 20 and 30 weeks of age (n = 10 mice per genotype). Optical coherence tomography (OCT) for retinal thickness assessment, Fundus Autofluorescence Imaging (FAF) for aggregate visualization, and electroretinogram (ERG) for retinal neuronal electrical activity were performed. Aβ ELISA was also performed on retina and cortex to evaluate amyloid burden correlation.ResultMean retinal insoluble Aβ 1‐42 was significantly elevated in TgCRND8 mice relative to WT at 23 weeks (35 vs 4.2 pg/mL, P<0.05) and 42 weeks (77.9 vs 7.5 pg/mL, P<0.05), and correlated with insoluble cortical brain Aβ 1‐42 (Pearson’s r = 0.847, P = 0.001). Total retinal thickness was significantly higher in TgCRND8 mice relative to WT (233 µm vs 225 µm, P<0.01). Specifically, the retinal nerve fiber layer (RNFL) was thicker in TgCRND8 mice (28.5 vs 22.9 µm, P<0.01). FAF imaging revealed significant autofluorescent aggregate detection in TgCRND8 mice both in the RNFL (94.3 vs 59.8 spots, P<0.01) and outer plexiform layer (OPL) (87.8 vs 49.3 spots, P<0.01). Lastly ERG revealed reduced b wave amplitude in TgCRND8 mice relative to WT (197.45 vs 457.9 µV, P<0.001) and photopic negative response (PhNR) wave amplitude (8.2 µm vs 25.7 457.9 µV, P<0.001). These values are indicative of dysfunctional bipolar and retinal ganglion cell electrical activity.ConclusionTgCRND8 mice have functional changes in retina thickness, FAF lipofuscin deposition, and ERG, which may prove invaluable as biomarkers for pre‐clinical AD diagnosis, monitoring and drug efficacy trials.

Targeted nanotheranostics for the treatment of epilepsy through in vivo hijacking of locally activated macrophages

Epilepsy refers to a disabling neurological disorder featured by the long-term and unpredictable occurrence of seizures owing to abnormal excessive neuronal electrical activity and is closely linked to unresolved inflammation, oxidative stress, and hypoxia. The difficulty of accurate localization and targeted drug delivery to the lesion hinders the effective treatment of this disease. The locally activated inflammatory cells in the epileptogenic region offer a new opportunity for drug delivery to the lesion. In this work, CD163-positive macrophages in the epileptogenic region were first harnessed as Trojan horses after being hijacked by targeted albumin manganese dioxide nanoparticles, which effectively penetrated the brain endothelial barrier and delivered multifunctional nanomedicines to the epileptic foci. Hence, accumulative nanoparticles empowered the visualization of the epileptogenic lesion through microenvironment-responsive MR T1-weight imaging of manganese dioxide. Besides, these manganese-based nanomaterials played a pivotal role in shielding neurons from cell apoptosis mediated by oxidative stress and hypoxia. Taken together, the present study provides an up-to-date approach for integrated diagnosis and treatment of epilepsy and other hypoxia-associated inflammatory diseases. Statement of significanceThe therapeutic effects of antiepileptic drugs (AEDs) are hindered by insufficient drug accumulation in the epileptic site. Herein, we report an efficient strategy to use locally activated macrophages as carriers to deliver multifunctional nanoparticles to the brain lesion. As MR-responsive T1 contrast agents, multifunctional BMC nanoparticles can be harnessed to accurately localize the epileptogenic region with high sensitivity and specificity. Meanwhile, catalytic nanoparticles BMC can synergistically scavenge ROS, generate O2 and regulate neuroinflammation for the protection of neurons in the brain.

The inverse stochastic resonance in a small-world neuronal network under electromagnetic stimulation

Electromagnetic stimulation is an important neuromodulation technique that modulates the electrical activity of neurons and affects cortical excitability for the purpose of modulating the nervous system. The phenomenon of inverse stochastic resonance is a response mechanism of the biological nervous system to external signals and plays an important role in the signal processing of the nervous system. In this paper, a small-world neural network with electrical synaptic connections was constructed, and the inverse stochastic resonance of the small-world neural network under electromagnetic stimulation was investigated by analyzing the dynamics of the neural network. The results showed that: the Levy channel noise under electromagnetic stimulation could cause the occurrence of inverse stochastic resonance in small-world neural networks; the characteristic index and location parameter of the noise had significant effects on the intensity and duration of the inverse stochastic resonance in neural networks; the larger the probability of randomly adding edges and the number of nearest neighbor nodes in small-world networks, the more favorable the anti-stochastic resonance was; by adjusting the electromagnetic stimulation parameters, a dual regulation of the inverse stochastic resonance of the neural network can be achieved. The results of this study provide some theoretical support for exploring the regulation mechanism of electromagnetic nerve stimulation technology and the signal processing mechanism of nervous system.

Autism spectrum disorder detection using variable frequency complex demodulation of the electroretinogram

The early diagnosis of neurodevelopmental conditions such as autism spectrum disorder (ASD), is an unmet need. One difficulty is the identification of a biological signal that relates to the ASD phenotype. The electroretinogram (ERG) waveform has been identified as a possible signal that could categorize neurological conditions such as ASD. The ERG waveform is derived from the electrical activity of photoreceptors and retinal neurons in response to a brief flash of light and provides an indirect 'window' into the central nervous system. Traditionally, the waveform is analyzed in the time-domain, but more recently time-frequency spectrum (TFS) analysis of ERG has been successfully carried out using discrete wavelet transformation (DWT) to characterize the morphological features of the signal. In this study, we propose the use of a high resolution TFS technique, namely variable frequency complex demodulation (VFCDM), to decompose the ERG waveform based on two signal flash strengths to build machine learning (ML) models to categorize ASD. ERG waveforms from N = 217 subjects (71 ASD, 146 control), at two different flash strengths, 446 and 113 Troland seconds (Td.s), from both right and left eyes were included. We analyzed the raw ERG waveforms using DWT and VFCDM. We computed features from the TFSs and trained ML models such as Random Forest, Gradient Boosting, Support Vector Machine to classify ASD from controls. ML models were validated using a subject independent validation strategy, and we found that the ML models with VFCDM features outperformed models using the DWT, achieving an area under the receiver operating characteristics curve of 0.90 (accuracy = 0.81, sensitivity = 0.85, specificity = 0.78). We found that the higher frequency range (80–300 Hz) included more relevant information for classifying ASD compared to the lower frequencies. We also found that the stronger flash strength of 446 Td.s in the right eye provided the best classification result which supports VFCDM analysis of the ERG waveform as a potential tool to aid in the identification of the ASD phenotype.

Dynamic analysis of epileptic seizures caused by energy failure after ischemic stroke

Energy is essential for neuronal electrical activity. An inadequate energy supply affects ion homeostasis and even induces epileptic seizures. Ischemic stroke is an important cause of energy failure and further leads to seizures. However, few computational models have focused on the impact of energy failure caused by ischemic stroke on epileptic seizures. To investigate the mechanism, we established a detailed biophysical model consisting of a neuron, an astrocyte, a capillary, and the extracellular space. First, we studied the effect of energy failure caused by ischemic stroke on neuronal discharge. The results demonstrate that ischemic stroke could cause spontaneous seizures and stimulate seizures of neurons, and prove that the cause of epileptic seizures is the destruction of the ion concentration gradient caused by energy failure. More importantly, we investigated the impact of energy failure on energy metabolism and found that compared with the normal discharge, the main energy that neurons depend on in epileptic seizures after ischemic stroke changes from lactate to glucose, and the astrocyte-neuron lactate shuttle (ANLS) is of great significance. Finally, we investigated the mechanism of inhibiting epileptic seizures, and the results revealed that inhibiting the LDH process in astrocytes and enhancing the ability of astrocytes to ingest extracellular glutamate are beneficial for inhibiting neuronal seizures. Most of the results are consistent with the experimental conclusion, and the results also reveal that astrocytes have neuroprotective effects and are a good target for inhibiting epileptic seizures.

Risk of seizure recurrence in children with new-onset afebrile seizure

BACKGROUND A seizure is a brief change in the normal neuronal electrical activity of the brain that causes changes in consciousness, perception, behavior, or movement. This study aimed to evaluate clinical findings, initial electroencephalography (EEG), and brain imaging findings as predictors of seizure recurrence after the first nonfebrile seizure.
 METHODS This prospective follow-up study was conducted at Azadi Teaching Hospital, Kirkuk from July 2019 to January 2022 and enrolled 150 patients, ranging from 1 month to 15 years of age, who presented with their first afebrile seizure. The seizure types were classified based on the International League Against Epilepsy in 2017. A brain imaging with EEG was performed within 72 hours after admission.
 RESULTS The median age of the patients was 5 years. A higher risk of seizure recurrence occurred in patients with focal seizure (relative risk [RR] = 6.604) (95% confidence interval [CI] 3.975–10.971), seizure occurrence at sleep (RR = 3.815) (95% CI 2.410–6.039), an abnormal neurological presentation such as Todd’s paralysis (RR = 1.739) (95% CI 1.252–2.415), a positive family history of seizures (RR = 2.333) (95% CI 1.598–3.408), abnormal EEG (RR = 0.171) (95% CI 0.092–0.318), and abnormal brain image findings (RR = 0.681) (95% CI 0.492–0.941) within 72 hours. Seizure recurrence was not correlated with sex.
 CONCLUSIONS Early and late childhood new-onset afebrile seizures with a positive family history, focal epilepsy, seizure during sleep, prolonged attack duration with frequent attacks within 24 hours, and abnormal initial EEG and brain image had a high risk of seizure recurrence.

FRI275 Glutamate Receptor Agonists Stimulate Kisspeptin Neurons In The Arcuate Nucleus Of The Hypothalamus

Abstract Disclosure: R. Bearss: None. R. Piet: None. KNDy neurons co-express kisspeptin, neurokinin B (NKB), dynorphin A (Dyn A), and glutamate. These neurons, located in the arcuate nucleus of the hypothalamus, drive pulsatile gonadotropin releasing hormone (GnRH) secretion. This eventually promotes pulsatile gonadotropin hormone release from the anterior pituitary, important for fertility in both sexes. The current hypothesized mechanism for pulse generation involves KNDy neuron interconnectivity and reciprocal regulation through the combined actions of NKB, DynA and glutamate to coordinate KNDy neuron activity. There is evidence that KNDy neurons express NKB, Dyn A and glutamate receptors and that NKB stimulates KNDy neuron electrical activity while Dyn A suppresses it. There is also evidence that ionotropic glutamate receptor antagonists can inhibit KNDy neuron coordinated activity and pulsatile gonadotropin hormone release, indicating that glutamatergic neurotransmission plays a significant role in activity coordination. The purpose of the following experiments was to investigate the response of KNDy neurons to varied glutamate receptor activation. We used calcium imaging to monitor the activity of KNDy neurons in brain slices. We crossed Kiss1-Cre mice—expressing Cre recombinase (Cre) in kisspeptin neurons—with Cre-dependent GCaMP6f mice to generate Kiss1-Cre x GCaMP6f mice that express GCaMP6f in kisspeptin neurons. GCaMP6f fluorescence increases when binding to intracellular calcium and can, thus, be used as an inferential marker of electrical activity. Coronal brain slices (200 µm thickness) obtained from male Kiss1-cre x GCaMP6f mice and containing the arcuate nucleus were placed in a recording chamber under an epifluorescence microscope. KNDy neurons were exposed for 2 minutes to a bath application of either the ionotropic glutamate receptor agonist α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 10µM), the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA, 50µM), or the group 1 metabotropic glutamate receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG, 50µM). AMPA, NMDA, and DHPG increased KNDy neuron fluorescence by 7.8±0.5% (n=113 in 7 slices from 6 mice), 7.5±0.5% (n=154 in 6 slices from 5 mice), and 6.1±0.7% (n=159 in 7 slices from 5 mice) respectively. All cells that were excited by NMDA or DHPG were also excited by AMPA. These experiments provide evidence that activation of ionotropic AMPA and NMDA receptors as well as group 1 mGluRs stimulate KNDy neuron activity. Further investigation into the precise role of individual glutamate receptor subtypes on KNDy neuron coordinated activity is needed. Presentation: Friday, June 16, 2023

Alternating current stimulation promotes neurite outgrowth and plasticity in neurons through activation of the PI3K/AKT signaling pathway.

As a commonly used physical intervention, electrical stimulation (ES) has been demonstrated to be effective in the treatment of central nervous system disorders. Currently, researchers are studying the effects of electrical stimulation on individual neurons and neural networks, which are dependent on factors such as stimulation intensity, duration, location, and neuronal properties. However, the exact mechanism of action of electrical stimulation remains unclear. In some cases, repeated or prolonged electrical stimulation can lead to changes in the morphology or function of the neuron. In this study, immunofluorescence staining and Sholl analysis are used to assess changes in the neurite number and axon length to determine the optimal pattern and stimulation parameters of ES for neurons. Neuronal death and plasticity are detected by TUNEL staining and microelectrode array assays, respectively. mRNA sequencing and bioinformatics analysis are applied to predict the key targets of the action of ES on neurons, and the identified targets are validated by western blot analysis and qRT-PCR. The effects of alternating current stimulation (ACS) on neurons are more significant than those of direct current stimulation (DCS), and the optimal parameters are 3 μA and 20 min. ACS stimulation significantly increases the number of neurites, the length of axons and the spontaneous electrical activity of neurons, significantly elevates the expression of growth-associated protein-43 (GAP-43) without significant changes in the expression of neurotrophic factors. Furthermore, application of PI3K/AKT-specific inhibitors significantly abolishes the beneficial effects of ACS on neurons, confirming that the PI3K/AKT pathway is an important potential signaling pathway in the action of ACS.