Neural Circuits Research Articles

Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) imposes a significant burden on patients, and the volume of hematoma plays a crucial role in determining the severity and prognosis of ICH. Although significant recent progress has been made in understanding the cellular and molecular mechanisms of surrounding brain tissue in ICH, our current knowledge regarding the precise impact of hematoma volumes on neural circuit damage remains limited. Here, using a viral tracing technique in a mouse model of striatum ICH, two distinct patterns of injury response were observed in upstream connectivity, characterized by both linear and nonlinear trends in specific brain areas. Notably, even low-volume hematomas had a substantial impact on downstream connectivity. Neurons in the striatum-ICH region exhibited heightened excitability, evidenced by electrophysiological measurements and changes in metabolic markers. Furthermore, a strong linear relationship (R2 = 0.91) was observed between hematoma volumes and NFL damage, suggesting a novel biochemical index for evaluating changes in neural injury. RNA sequencing analysis revealed the activation of the MAPK signaling pathway following hematoma, and the addition of MAPK inhibitor revealed a decrease in neuronal circuit damage, leading to alleviation of motor dysfunction in mice. Taken together, our study highlights the crucial role of hematoma size as a determinant of circuit injury in ICH. These findings have important implications for clinical evaluations and treatment strategies, offering opportunities for precise therapeutic approaches to mitigate the detrimental effects of ICH and improve patient outcomes.

Sex differences in neuronal activation in the cortex and midbrain during quinine-adulterated alcohol intake.

Continued alcohol consumption despite negative consequences is a core symptom of alcohol use disorder. This is modeled in mice by pairing negative stimuli with alcohol, such as adulterating alcohol solution with quinine. Mice consuming alcohol under these conditions are considered to be engaging in aversion-resistant intake. Previously, we have observed sex differences in this behavior, with females more readily expressing aversion-resistant consumption. We also identified three brain regions that exhibited sex differences in neuronal activation during quinine-alcohol drinking: ventromedial prefrontal cortex (vmPFC), posterior insular cortex (PIC), and ventral tegmental area (VTA). Specifically, male mice showed increased activation in vmPFC and PIC, while females exhibited increased activation in VTA. In this study, we aimed to identify what specific type of neurons are activated in these regions during quinine-alcohol drinking. We assessed quinine-adulterated alcohol intake using the two-bottle choice procedure. We also utilized RNAscope in situ hybridization in the three brain regions that previously exhibited a sex difference to examine colocalization of Fos, glutamate, GABA, and dopamine. Females showed increased aversion-resistant alcohol consumption compared to males. We also found that males had higher colocalization of glutamate and Fos in vmPFC and PIC, while females had greater dopamine and Fos colocalization in the VTA. Collectively, these experiments suggest that glutamatergic output from the vmPFC and PIC may have a role in suppressing, and dopaminergic activity in the VTA may promote, aversion-resistant alcohol consumption. Future experiments will examine neuronal circuits that contribute to sex differences in aversion resistant consumption.

Updated Toolbox for Assessing Neuronal Network Reconstruction after Cell Therapy

Updated Toolbox for Assessing Neuronal Network Reconstruction after Cell Therapy

Ventral subiculum promotes wakefulness through several pathways in male mice.

The ventral subiculum (vSUB), the major output structure of the hippocampal formation, regulates motivation, stress integration, and anxiety-like behaviors that rely on heightened arousal. However, the roles and underlying neural circuits of the vSUB in wakefulness are poorly known. Using in vivo fiber photometry and multichannel electrophysiological recordings in mice, we found that the vSUB glutamatergicneurons exhibited highactivities during wakefulness. Moreover, activation of vSUB glutamatergic neurons caused an increase in wakefulness and anxiety-like behaviors and induced a rapid transition from sleep to wakefulness. In addition, optogenetic stimulation of vSUB glutamatergic terminals and retrograde-targeted chemogenetic activation of vSUB glutamatergic neurons revealed that vSUB promoted arousal by innervating the lateral hypothalamus (LH), nucleus accumbens (NAc) shell, and prefrontal cortex (PFC). Nevertheless, local microinjection of dopamine D1 or D2/D3 receptor antagonist blocked thewake-promoting effect induced by chemogenetic activation of vSUB pathways. Finally, chemogenetic inhibition of vSUB glutamatergic neurons decreased arousal. Altogether, our findings reveal a prominent contribution of vSUB glutamatergic neurons to the control of wakefulness through several pathways.

At the Basis of Brain Malformations: Brain Plasticity, Developmental Neurobiology, and Considerations for Rehabilitation

AbstractFrom early age in the human brain occurs plasticity process that influences its development. The functioning of the brain is governed by its neuronal connectivity and the synaptic dynamics of these connections. A neuron, over thousands of synapses, can receive a large number of inputs and produce different outputs leading to the consolidation and integration of memory. Synaptic plasticity is the set of experience-dependent changes in neuronal pathways that support acquired habits. It is the ability of the nervous system to reshape connectivity between neurons, changing the functional and structural organization of neuronal circuits that allows us to adapt to the multiple and continuous changes in the environment and leading to processes such as cognitive development and the ability to learn. Synaptic plasticity is mainly due to short- and long-term mechanisms. Short-term synaptic plasticity refers to changes in synaptic strength that occurs very quickly (from one-thousandth of a second to 5 minutes) and are temporary and decay over minutes (maximum 30 minutes). Long-term synaptic plasticity is defined by a long-lasting, activity-dependent change in synaptic efficacy, last from hours up to a lifetime (from 30 minutes to weeks, months, and years) and is thought to constitute the basis of learning and memory. A significant difference occurs in the nature of the change; short-term plasticity adds only a functional change, whereas long-term plasticity causes not only functional but also structural changes. Aside from genetic factors and metabolic processes, brain development is mediated also by environmental factors. Interaction with the environment plays a key role in the development and growth of neural networks and neuroplasticity. Environmental interactions that can modify and increase the development of neural networks and intelligence in children are several and are herein discussed.

Insight into the pathophysiological advances and molecular mechanisms underlying cerebral stroke: current status.

Molecular pathways involved in cerebral stroke are diverse. The major pathophysiological events that are observed in stroke comprises of excitotoxicity, oxidative stress, mitochondrial damage, endoplasmic reticulum stress, cellular acidosis, blood-brain barrier disruption, neuronal swelling and neuronal network mutilation. Various biomolecules are involved in these pathways and several major proteins are upregulated and/or suppressed following stroke. Different types of receptors, ion channels and transporters are activated. Fluctuations in levels of various ions and neurotransmitters have been observed. Cells involved in immune responses and various mediators involved in neuro-inflammation get upregulated progressing the pathogenesis of the disease. Despite of enormity of the problem, there is not a single therapy that can limit infarction and neurological disability due to stroke. This is because of poor understanding of the complex interplay between these pathophysiological processes. This review focuses upon the past to present research on pathophysiological events that are involved in stroke and various factors that are leading to neuronal death following cerebral stroke. This will pave a way to researchers for developing new potent therapeutics that can aid in the treatment of cerebral stroke.

Distinct roles of excitatory and inhibitory neurons in the medial prefrontal cortex in the expression and reconsolidation of methamphetamine-associated memory in male mice.

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

Inhibitory subpopulations in preBötzinger Complex play distinct roles in modulating inspiratory rhythm and pattern.

Inhibitory neurons embedded within mammalian neural circuits shape breathing, walking, and other rhythmic motor behaviors. At the core of the neural circuit controlling breathing is the preBötzinger Complex (preBötC), where GABAergic (GAD1/2+) and glycinergic (GlyT2+) neurons are functionally and anatomically intercalated among glutamatergic Dbx1-derived (Dbx1+) neurons that generate rhythmic inspiratory drive. The roles of these preBötC inhibitory neurons in breathing remain unclear. We first characterized the spatial distribution of molecularly-defined preBötC inhibitory subpopulations in male and female neonatal double reporter mice expressing either tdTomato or EGFP in GlyT2+, GAD1+, or GAD2+ neurons. We found that the majority of preBötC inhibitory neurons expressed both GlyT2 and GAD2 while a much smaller subpopulation also expressed GAD1. To determine the functional role of these subpopulations, we used holographic photostimulation, a patterned illumination technique, in rhythmically active medullary slices from neonatal Dbx1tdTomato;GlyT2EGFP and Dbx1tdTomato;GAD1EGFP double reporter mice of either sex. Stimulation of 4 or 8 preBötC GlyT2+ neurons during endogenous rhythm prolonged the interburst interval in a phase-dependent manner and increased the latency to burst initiation when bursts were evoked by stimulation of Dbx1+ neurons. In contrast, stimulation of 4 or 8 preBötC GAD1+ neurons did not affect interburst interval or latency to burst initiation. Instead, photoactivation of GAD1+ neurons during the inspiratory burst prolonged endogenous and evoked burst duration and decreased evoked burst amplitude. We conclude that GlyT2+/GAD2+ neurons modulate breathing rhythm by delaying burst initiation while a smaller GAD1+ subpopulation shapes inspiratory patterning by altering burst duration and amplitude.Significance Statement Inhibition is critical for control of rhythmic motor behaviors, such as breathing, walking, and chewing. We reveal functional differences among embedded preBötC inhibitory micro-cir-cuits that contribute to excitation-inhibition balance governing distinct processes in the breathing motor program. We develop approaches for high throughput analysis of spatial distributions of neurons in tissue and for dynamic functional manipulations via an important extension of holographic photostimulation to sequences of patterns that more closely mimics physiological neural activity. Our study challenges the current understanding of the role of inhibition in breathing and provides novel insights into specific roles of inhibitory neurons in neural circuits controlling breathing that are applicable to other rhythmic motor behaviors in health and disease.

Critical appraisal of how COVID-19 infection and imposed lockdowns have impacted gastroesophageal reflux: A review.

Previous literature has demonstrated that COronaVIrus Disease of 2019 (COVID-19) impacts an individual gastrointestinal tract (GIT), causing symptoms like nausea, diarrhea, and loss of appetite. Severe acute respiratory syndrome coronavirus RNA has been discovered in the stool of infected individuals in earlier research. It was discovered that severe acute respiratory syndrome coronavirus was significantly expressed in the GIT, indicating that the virus can also infect the digestive system. Angiotensin-converting enzyme 2 functions as the viral receptor. The chronic illness known as gastroesophageal reflux disease (GERD) is typified by frequent reflux of stomach acid into the esophagus. By triggering the sensitized esophageal-bronchial neuronal circuit or aspirating into the airways (microaspiration), GER exacerbates respiratory diseases. Aspiration is a well-known risk to be considered when treating patients in intensive care units. Strong genetic correlations have been identified between COVID-19 infection and GERD susceptibility, suggesting a shared genetic basis for both conditions. Nonetheless, even though GERD, extraesophageal reflex, and COVID-19 have a number of significant risk factors and exhibit similar symptoms, the relationship between these illnesses has not yet been examined in depth. This review is the first of its kind to critically examine the association between the COVID-19 epidemic and GER and its associated diseases. The key objective of this work is to promote the creation of prevention plans, treatment plans, and guidelines while also enhancing and optimizing our understanding of the relationship between COVID-19 and GERs.

The role and mechanism of 5-HTDRN-BNST neural circuit in anxiety and fear lesions

Central 5-hydroxytryptaminergic dorsal raphe nucleus (5-HTDRN)-bed nucleus of stria terminalis (BNST) neural circuit dysfunction is one of the important neurobiological basis of anxiety and fear disorders. Under stress, 5-hydroxytryptamine (5-HT) neurons act on BNST receptors to attenuate anxiety and fear responses or enhance anxiety and fear. In BNST, corticotropin releasing factor neurons play a role in regulating emotions by reversely regulating excitatory or inhibitory 5-HT neurons. The composition of 5-HTDRN-BNST neural circuit, the pathological changes of 5-HTDRN-BNST neural circuit function damage under stress, and the effects of 5-HTDRN-BNST neural circuit on anxiety disorder, panic disorder and post-traumatic stress disorder were analyzed and are summarized in this paper. The characteristics of functional changes of the neural circuit and its effects on brain functional activities provide a basis and ideas for the treatment of anxiety and fear disorders through the regulation of 5-HTDRN-BNST neural circuit, and they also provide a new perspective for understanding the pathological mechanism of such diseases.

Low power nanoscale S-FED based single ended sense amplifier applied in integrate and fire neuron circuit

Current advancements in neuromorphic computing systems are focused on decreasing power consumption and enriching computational functions. Correspondingly, state-of-the-art system-on-chip developers are encouraged to design nanoscale devices with minimum power dissipation and high-speed operation. This paper deals with designing a sense amplifier based on side-contacted field-effect diodes to reduce the power-delay product (PDP) and the noise susceptibility, as critical factors in neuron circuits. Our findings reveal that both static and dynamic power consumption of the S-FED-based sense amplifier, equal to 1.86 μW and 1.92 fW/GHz, are × 243.03 and × 332.83 lower than those of the conventional CMOS counterpart, respectively. While the sense-amplifier circuit based on CMOS technology undergoes an output voltage deviation of 170.97 mV, the proposed S-FED-based one enjoys a minor output deviation of 27.31 mV. Meanwhile, the superior HIGH-level and LOW-level noise margins of the S-FED-based sense amplifier to the CMOS counterparts (∆NMH = 70 mV and ∆NML = 120 mV), respectively, can ensure the system-level operation stability of the former one. Subsequent to the attainment of an area-efficient, low-power, and high-speed S-FED-based sense amplifier (PDP = 187.75 × 10–18 W s) as a fundamental building block, devising an innovative integrate-and-fire neuron circuit based on S-FED paves the way to realize a new generation of neuromorphic architectures. To shed light on this context, an S-FED-based integrate-and-fire neuron circuit is designed and analyzed utilizing a sense amplifier and feedback loop to enhance spiking voltage and subsequent noise immunity in addition to an about fourfold increase in firing frequency compared to CMOS-based ones.

Comparative study between two artificial intelligence techniques (NN and SVM) applied in fault diagnosis of Wind Turbine

This paper addresses the application of artificial intelligence (AI) techniques for the classification of faults in wind turbine. Wind Energy Conversion Systems have become a focal point in the research of renewable energy sources. Reliability of wind turbine is critical to extract this maximum amount of energy from the wind. Many condition monitoring techniques that are based on steady-state analysis are being applied to wind generators. Bearing faults in this generator causes mechanical vibrations and the variations in the air gap density. The air gap flux density is modulated and currents are generated at different frequencies related to the mechanical vibrations. Characteristic bearing frequencies are associated with the physical construction of bearing and its failure mode. Classical spectral analysis using the Fourier transform was used to detect different bearing failure modes. The magnitudes of the frequencies components formed by the bearing defect are small compared to the rest of the current spectrum. This large difference in magnitude makes difficult the detection and classification of bearing faults. In this paper, we show that the utilization of different approaches of artificial intelligence such as neuronal network (NN) and support vector machines (SVM) can be discriminate different failure modes and gives a good basis for an automatic and non-invasive condition monitoring for wind turbine.

Anti-artifacts techniques for neural recording front-ends in closed-loop brain-machine interface ICs

In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends.

Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics

Chronic pruritus that lasts for over 6 weeks can present in various forms, like papules, nodules, and plaque types, with prurigo nodularis (PN) being the most prevalent. The pathogenesis of PN involves the dysregulation of immune cell–neural circuits and is associated with peripheral neuropathies, possibly due to chronic scratching. PN is a persistent and challenging condition, involving complex interactions among the skin, immune system, and nervous system. Lesional skin in PN exhibits the infiltration of diverse immune cells like T cells, eosinophils, macrophages, and mast cells, leading to the release of inflammatory cytokines and itch-inducing substances. Activated sensory nerve fibers aggravate pruritus by releasing neurotransmitters, perpetuating a vicious cycle of itching and scratching. Traditional treatments often fail, but recent advancements in understanding the inflammatory and itch transmission mechanisms of PN have paved the way for innovative therapeutic approaches, which are explored in this review.

Exercise Influences the Brain’s Metabolic Response to Chronic Cocaine Exposure in Male Rats

Cocaine use is associated with negative health outcomes: cocaine use disorders, speedballing, and overdose deaths. Currently, treatments for cocaine use disorders and overdose are non-existent when compared to opioid use disorders, and current standard cocaine use disorder treatments have high dropout and recidivism rates. Physical exercise has been shown to attenuate addiction behavior as well as modulate brain activity. This study examined the differential effects of chronic cocaine use between exercised and sedentary rats. The effects of exercise on brain glucose metabolism (BGluM) following chronic cocaine exposure were assessed using Positron Emission Tomography (PET) and [18F]-Fluorodeoxyglucose (FDG). Compared to sedentary animals, exercise decreased metabolism in the SIBF primary somatosensory cortex. Activation occurred in the amygdalopiriform and piriform cortex, trigeminothalamic tract, rhinal and perirhinal cortex, and visual cortex. BGluM changes may help ameliorate various aspects of cocaine abuse and reinstatement. Further investigation is needed into the underlying neuronal circuits involved in BGluM changes and their association with addiction behaviors.

Multiple scroll attractors and multistability in the collective dynamics of a four chain coupled hopfield inertial neuron network: analysis and circuit design investigations

This work deals with the chain bidirectional coupling of four inertial Hopfield neurons. Each of our cells taken alone is modeled by a second order differential equation having three resting points. Coupling these neurons helps increasing the number of fixed points that is related to the amount of memory assigned to the network. The system having a hyperbolic tangent as nonlinearity is investigated with the help of suitable nonlinear dynamical tools like bifurcation diagrams, Lyapunov exponent diagrams and phase portraits to resort the richness of the model. As the coupling adds the amount of equilibriums, it also helps in generating multiple scroll attractors. The system that was unable of oscillation presents firing patterns such as parallel branches, coexistence of up to sixteen attractors in the phase plane, extreme events and Hopf bifurcation to name a few. All these features are discovered when observing the coupling strengths, the dissipation coefficient and when programming initial states around sensitive equilibriums. The electronic version of the four-chain coupled inertial neurons system is provided and simulated on Pspice with the aim to confirm the results obtained in the numerical scheme.

Effects of spike-time-dependent plasticity on stochastic resonance in excitatory-inhibitory neuronal networks

Effects of spike-time-dependent plasticity on stochastic resonance in excitatory-inhibitory neuronal networks

Automated Crystallization Monitoring in Material Development using Computer Vision and Neuronal Networks

AbstractCrystallization is critical in producing various substances in the food and pharmaceutical industries. The process begins with nucleation from a supersaturated solution, followed by the directed movement of solute molecules toward the newly formed nuclei. This movement is influenced by different factors such as molecular attraction and thermodynamic properties, which influence the resulting crystal size and shape. This paper presents an automated monitoring approach for the growth process of crystallization from saturated solutions. To monitor such a process, a combination of artificial intelligence and computer vision is used. The approach was developed for application in material research to automate the processing of numerous samples, which would otherwise require laboratory personnel.

Hypergraph-Based Numerical Spiking Neural Membrane Systems with Novel Repartition Protocols.

The classic spiking neural P (SN P) systems abstract the real biological neural network into a simple structure based on graphs, where neurons can only communicate on the plane. This study proposes the hypergraph-based numerical spiking neural membrane (HNSNM) systems with novel repartition protocols. Through the introduction of hypergraphs, the HNSNM systems can characterize the high-order relationships among neurons and extend the traditional neuron structure to high-dimensional nonlinear spaces. The HNSNM systems also abstract two biological mechanisms of synapse creation and pruning, and use plasticity rules with repartition protocols to achieve planar, hierarchical and spatial communications among neurons in hypergraph neuron structures. Through imitating register machines, the Turing universality of the HNSNM systems is proved by using them as number generating and accepting devices. A universal HNSNM system consisting of 41 neurons is constructed to compute arbitrary functions. By solving NP-complete problems using the subset sum problem as an example, the computational efficiency and effectiveness of HNSNM systems are verified.

Multifunctional Hierarchical Nanoplatform with Anisotropic Bimodal Mesopores for Effective Neural Circuit Reconstruction after Spinal Cord Injury.

A persistent inflammatory response, intrinsic limitations in axonal regenerative capacity, and widespread presence of extrinsic axonal inhibitors impede the restoration of motor function after a spinal cord injury (SCI). A versatile treatment platform is urgently needed to address diverse clinical manifestations of SCI. Herein, we present a multifunctional nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after SCI. The hierarchical nanoplatform features of a Janus structure consist of dual compartments of hydrophilic mesoporous silica (mSiO2) and hydrophobic periodic mesoporous organosilica (PMO), each possessing distinct pore sizes of 12 and 3 nm, respectively. Unlike traditional hierarchical mesoporous nanomaterials with dual-mesopores interlaced with each other, the two sets of mesopores in this Janus nanoplatform are spatially independent and possess completely distinct chemical properties. The Janus mesopores facilitate controllable codelivery of dual drugs with distinct properties: the hydrophilic macromolecular enoxaparin (ENO) and the hydrophobic small molecular paclitaxel (PTX). Anchoring with CeO2, the resulting mSiO2&PMO-CeO2-PTX&ENO nanoformulation not only effectively alleviates ROS-induced neuronal apoptosis but also enhances microtubule stability to promote intrinsic axonal regeneration and facilitates axonal extension by diminishing the inhibitory effect of extracellular chondroitin sulfate proteoglycans. We believe that this functional dual-mesoporous nanoplatform holds significant potential for combination therapy in treating severe multifaceted diseases.