Neuronal Components Research Articles

Optogenetic Methods to Investigate Brain Alterations in Preclinical Models.

Investigating the neuronal dynamics supporting brain functions and understanding how the alterations in these mechanisms result in pathological conditions represents a fundamental challenge. Preclinical research on model organisms allows for a multiscale and multiparametric analysis in vivo of the neuronal mechanisms and holds the potential for better linking the symptoms of a neurological disorder to the underlying cellular and circuit alterations, eventually leading to the identification of therapeutic/rescue strategies. In recent years, brain research in model organisms has taken advantage, along with other techniques, of the development and continuous refinement of methods that use light and optical approaches to reconstruct the activity of brain circuits at the cellular and system levels, and to probe the impact of the different neuronal components in the observed dynamics. These tools, combining low-invasiveness of optical approaches with the power of genetic engineering, are currently revolutionizing the way, the scale and the perspective of investigating brain diseases. The aim of this review is to describe how brain functions can be investigated with optical approaches currently available and to illustrate how these techniques have been adopted to study pathological alterations of brain physiology.

LGG-28. Rapid symptomatic improvement for a patient treated with BRAF inhibition for BRAFV600E mutated ganglioglioma

BACKGROUND: Biologically targeted agents such as the BRAF inhibitor dabrafenib are now used to treat progressive low-grade glioma (LGG), but the effect of these agents on the neurologic symptoms that accompany LGGs is poorly understood. CASE: A 21-year-old male was diagnosed with medullary ganglioglioma (GG) after presenting with persistent vertigo and positional headaches. Immunohistochemistry was consistent with BRAF V600E mutation and dabrafenib was started. The patient had resolution of his neurologic symptoms within 3 weeks of treatment initiation; surveillance MRI several months later demonstrated interval decrease in tumor size. The patient remained on therapy for 2 years. Several days after planned drug discontinuation the patient had re-emergence of persistent vertigo that impaired his ability to work. Repeat imaging two months later demonstrated an increase in tumor size and solid enhancement along tumor margins. He was restarted on dabrafenib. Within one week, he again had complete resolution of his vertigo. DISCUSSION: Gangliogliomas are comprised of mixed neuronal and glial components and associated with epilepsy, headache and other localizing neurologic symptoms. In this report, we describe clinical and radiographic response from single-therapy dabrafenib in a patient with BRAF V600E+ GG, along with a very rapid resolution of neurologic symptoms upon initiation of the drug and recrudescence shortly following cessation of therapy. The symptoms subsided within a week of restarting dabrafenib, suggesting a separate, more rapid mechanism of symptom reversal than decline in tumor size. BRAF mutations have been identified in both the neuronal and glial components of ganglioglioma, suggesting that dabrafenib may provide symptomatic relief via inhibition of abberant neuronal processes. CONCLUSION: BRAF inhibitors can rapidly improve neurological symptoms via a rapid, not yet fully elucidated mechanism. Kinetics of this response suggest it is independent of effects on tumor volume and the degree of compression to tissue surrounding the tumor.

Preliminary Study on Safety Assessment of 10 Hz Transcranial Alternating Current Stimulation in Rat Brain

Assessment of the safety of transcranial electrical stimulation devices that contact the scalp and apply electrical stimulations to brain tissues is essential for the prevention of unexpected brain damage caused by electromagnetic fields. In particular, safety studies on transcranial alternating current stimulation (tACS) are needed for active applications to treat brain diseases and for the development of medical devices, because there is a lack of research on the safety of tACS, in contrast to transcranial direct current stimulation. In this study, the safety of tACS with selected parameters, i.e., a stimulation intensity of 1.0 to 2.0 mA, a frequency of 10 Hz, and a treatment time of 20 min, was examined at a preclinical stage using small animals (rats). The results of magnetic resonance imaging and histopathological imaging indicated that the conditions applied in this study provided safe tACS without damaging brain tissues or neuronal components in the acute phase. In addition, the temperature did not increase above 41 °C, which is a temperature limitation for contact-type medical devices, even after 20 min of tACS application.

Role of Environmental Toxicants on Neurodegenerative Disorders.

Neurodegeneration leads to the loss of structural and functioning components of neurons over time. Various studies have related neurodegeneration to a number of degenerative disorders. Neurological repercussions of neurodegeneration can have severe impacts on the physical and mental health of patients. In the recent past, various neurodegenerative ailments such as Alzheimer’s and Parkinson’s illnesses have received global consideration owing to their global occurrence. Environmental attributes have been regarded as the main contributors to neural dysfunction-related disorders. The majority of neurological diseases are mainly related to prenatal and postnatal exposure to industrially produced environmental toxins. Some neurotoxic metals, like lead (Pb), aluminium (Al), Mercury (Hg), manganese (Mn), cadmium (Cd), and arsenic (As), and also pesticides and metal-based nanoparticles, have been implicated in Parkinson’s and Alzheimer’s disease. The contaminants are known for their ability to produce senile or amyloid plaques and neurofibrillary tangles (NFTs), which are the key features of these neurological dysfunctions. Besides, solvent exposure is also a significant contributor to neurological diseases. This study recapitulates the role of environmental neurotoxins on neurodegeneration with special emphasis on major neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

Leucine-Rich Repeats and Transmembrane Domain 2 Controls Protein Sorting in the Striatal Projection System and Its Deficiency Causes Disturbances in Motor Responses and Monoamine Dynamics.

The striatum is involved in action selection, and its disturbance can cause movement disorders. Here, we show that leucine-rich repeats and transmembrane domain 2 (Lrtm2) controls protein sorting in striatal projection systems, and its deficiency causes disturbances in monoamine dynamics and behavior. The Lrtm2 protein was broadly detected in the brain, but it was enhanced in the olfactory bulb and dorsal striatum. Immunostaining revealed a strong signal in striatal projection output, including GABAergic presynaptic boutons of the SNr. In subcellular fractionation, Lrtm2 was abundantly recovered in the synaptic plasma membrane fraction, synaptic vesicle fraction, and microsome fraction. Lrtm2 KO mice exhibited altered motor responses in both voluntary explorations and forced exercise. Dopamine metabolite content was decreased in the dorsal striatum and hypothalamus, and serotonin turnover increased in the dorsal striatum. The prefrontal cortex showed age-dependent changes in dopamine metabolites. The distribution of glutamate decarboxylase 67 (GAD67) protein and gamma-aminobutyric acid receptor type B receptor 1 (GABABR1) protein was altered in the dorsal striatum. In cultured neurons, wild-type Lrtm2 protein enhanced axon trafficking of GAD67-GFP and GABABR1-GFP whereas such activity was defective in sorting signal-abolished Lrtm2 mutant proteins. The topical expression of hemagglutinin-epitope-tag (HA)-Lrtm2 and a protein sorting signal abolished HA-Lrtm2 mutant differentially affected GABABR1 protein distribution in the dorsal striatum. These results suggest that Lrtm2 is an essential component of striatal projection neurons, contributing to a better understanding of striatal pathophysiology.

Generation of vascularized brain organoids to study neurovascular interactions.

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.

Vibration detection in arthropods: Signal transfer, biomechanics and sensory adaptations

In arthropods, the detection of vibrational signals and stimuli is essential in several behaviours, including mate recognition and pair formation, prey detection, and predator evasion. These behaviours have been studied in several species of insects, arachnids, and crustaceans for vibration production and propagation in the environment. Vibration stimuli are transferred over the animals’ appendages and the body to vibrosensory organs. Ultimately, the stimuli are transferred to act on the dendrites of the mechanosensitive sensilla. We refer to these two different levels of transfer as macromechanics and micromechanics, respectively. These biomechanical processes have important roles in filtering and pre-processing of stimuli, which are not carried out by neuronal components of sensory organs. Also, the macromechanical transfer is posture-dependent and enables behavioural control of vibration detection. Diverse sensory organs respond to vibrations, including cuticular sensilla (slit sensilla, campaniform sensilla) and internal chordotonal organs. These organs provide various adaptations, as they occur at diverse body positions with different mechanical couplings as input pathways. Macromechanics likely facilitated evolution of vibrosensory organs at specific body locations. Thus, vibration detection is a highly complex sensory capacity, which employs body and sensory mechanics for signal filtering, amplification, and analysis of frequency, intensity and directionality.

Glioblastoma: Changing concepts in the WHO CNS5 classification.

Glioblastoma is the most common malignant central nervous system (CNS) tumor in adults. Acute common clinical symptoms include headache, seizure, behavior changes, focal neurological deficits, and signs of increased intracranial pressure. The classic MRI finding of glioblastoma is an irregularly shaped, rim-enhancing or ring-enhancing lesion with a central dark area of necrosis. This constellation of features correlates with microscopic findings of tumor necrosis and microvascular proliferation. Besides these common features, several well-recognized histological subtypes include giant cell glioblastoma, granular cell glioblastoma, gliosarcoma, glioblastoma with a primitive neuronal component, small cell glioblastoma, and epithelioid glioblastoma. While glioblastoma was historically classified as isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant groups, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and the fifth edition of the WHO Classification of Tumors of the Central Nervous System clearly updated the nomenclature to reflect glioblastoma to be compatible with wildtype IDH status only. Therefore, glioblastoma is now defined as "a diffuse, astrocytic glioma that is IDH-wildtype and H3-wildtype and has one or more of the following histological or genetic features: microvascular proliferation, necrosis, Telomerase reverse transcriptase promoter mutation, Epidermal growth factor receptor gene amplification, +7/-10 chromosome copy-number changes (CNS WHO grade 4)."

Sub-acute Toxicity and Safety Study of Mecca Myrrh (Commiphora opobalsamum) by Experimental Histological Analysis

Background: The native herbal medicinal products are vital source of the key medication; their excellent dogmatic safety study is of prime importance despite their strong validated evidence of efficacy.
 Aim: To study the sub-acute toxicity of Commiphora opobalsamum (CO) by histological analysis of vital organs.
 Methods: Twenty-four male Wister rats of 10-12 weeks age were used. Oral toxicity studies with repeated dose were accomplished in four group of rats, six rats were included in each group. Three groups of rats were administered CO orally in the graded doses of 250,500, and 1000 mg/kg/day once daily for 14 days Vs normal control. Determination the relative weight of vital organs and their histological changes were performed at the end of the study. Subsequently, the digital images of the CO - administered groups were equated with the control group.
 Results: Intriguingly, the relative weights of the vital organs, performed following 14 days of graded doses of CO given were equated with the control group, significant differences were not detected (p˃0.05). Furthermore, histological examination of the brain demonstrated no changes in its cellular neuronal components Regarding the heart, CO extract did not produce any histological changes, insignificant changes were observed in liver parenchyma of rats, regarding the kidney, no degenerative changes were noticed in glomerular tuft capillaries or renal tubular epithelium, conversely trivial changes were observed in liver parenchyma. Finally, no minor histological changes were observed in stomach (high dose) and spleen tissue of animals on comparison with the control group.
 Conclusion: Seemingly, the impressive outcome of this fundamental histological scrutiny of methanolic extract of CO demonstrated an imperative facet of safety and correspondingly displayed the key feature of its nontoxic medicinal application for short term supplementation.

Regulation of early cerebellar development.

The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three-layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons.

In situ analysis of acupuncture protecting dopaminergic neurons from lipid peroxidative damage in mice of Parkinson's disease.

ObjectivesAcupuncture stimulation has proven to protect dopaminergic neurons from oxidative damage in animal models of Parkinson's disease (PD), but it remains unclear about the in situ information of biochemical components in dopaminergic neurons. Here, we aimed to analyse in situ changes of biochemical components and lipid peroxidation levels in dopaminergic neurons in PD mice treated with acupuncture by synchrotron FTIR micro‐spectroscopy technique.Materials and MethodsAbout 9–10‐week‐old C57BL/6 mice were used to establish PD model by intraperitoneal injection of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP, 30 mg/kg for 5 days). Acupuncture stimulation was performed once a day for 12 days. Behaviour test was determined using the rotarod instrument. Biochemical compositions of dopaminergic neurons in substantia nigra pars compacta were analysed by synchrotron FTIR micro‐spectroscopy technique. The number and ultrastructure of dopaminergic neurons were respectively observed by immunofluorescence and transmission electron microscopy (TEM).ResultsWe found that the number and protein expression of dopaminergic neurons in MPTP‐treated mice were reduced by about half, while that in the mice treated by acupuncture were significantly restored. Acupuncture treatment also restored the motor ability of PD mice. The results of single cell imaging with synchrotron FTIR micro‐spectroscopy technique showed that the proportion of lipid in MPTP treated mice increased significantly. Especially the ratio of CH2 asymmetric stretching and CH3 asymmetric stretching increased significantly, suggesting that MPTP induced lipid peroxidation damage of dopaminergic neurons. It is also supported by the result of TEM, such as mitochondrial swelling or atrophy, loss of mitochondrial crests and mitochondrial vacuolization. Compared with MPTP treated mice, the proportion of lipid in acupuncture treated mice decreased and the mitochondrial structure was restored.ConclusionsAcupuncture can inhibit the level of lipid peroxides in dopaminergic neurons and protect neurons from oxidative damage. The study provides a promising method for in situ analysis of biochemical compositions in PD mice and reveals the mechanism of acupuncture in treating neurodegenerative diseases.

Effects of dendritic properties on spike train correlations in biophysically-based model neurons

A large number of studies have shown that the correlation of spike trains in paired neurons is a key indicator of functional connectivity. Acting as the important components of neurons, dendrites affect the generation of spike train and the transmission of signals by changing the transfer function of neurons. However, it is not clear how the intrinsic properties of dendrites influence the degree of correlation of neuronal spike trains. This paper used a biophysically-based two-compartment model to simulate the firing output of neurons that receive correlated input currents, quantify the relationship between the active and passive properties of dendrites and the pairwise spike train correlations. We found that increasing the proportion of dendritic area or the coupling conductance between two compartments increases the output correlation. It is also shown that decreasing the intracellular calcium concentration and the conductance of calcium activated outward potassium channel or increasing the conductance of sodium and potassium channel in dendritic compartment increases the output correlation. This results from the increase of the number of dendritic spikes due to changing dendritic intrinsic properties, which causes more internal current flowing into the soma from dendrites, thereby leading to an increase of somatic firing rate. Our results reveal the influence of the intrinsic characteristics of dendrites on firing output of individual neuron, which further influences the correlation between the spike trains of a pairs or population of neurons. This study is of great significance for understanding how neuronal intrinsic properties affect neural network coding.

An age-dependent mathematical model of neurofilament trafficking in healthy conditions.

Neurofilaments (Nfs) are the major structural component of neurons. Their role as a potential biomarker of several neurodegenerative diseases has been investigated in past years with promising results. However, even under physiological conditions, little is known about the leaking of Nfs from the neuronal system and their detection in the cerebrospinal fluid (CSF) and blood. This study aimed at developing a mathematical model of Nf transport in healthy subjects in the 20–90 age range. The model was implemented as a set of ordinary differential equations describing the trafficking of Nfs from the nervous system to the periphery. Model parameters were calibrated on typical Nf levels obtained from the literature. An age‐dependent function modeled on CSF data was also included and validated on data measured in serum. We computed a global sensitivity analysis of model rates and volumes to identify the most sensitive parameters affecting the model’s steady state. Age, Nf synthesis, and degradation rates proved to be relevant for all model variables. Nf levels in the CSF and in blood were observed to be sensitive to the Nf leakage rates from neurons and to the blood clearance rate, and CSF levels were also sensitive to rates representing CSF turnover. An additional parameter perturbation analysis was also performed to investigate possible transient effects on the model variables not captured by the sensitivity analysis. The model provides useful insights into Nf transport and constitutes the basis for implementing quantitative system pharmacology extensions to investigate Nf trafficking in neurodegenerative diseases.

Diabetic Retinopathy: From Animal Models to Cellular Signaling.

Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM), a metabolic disorder characterized by elevation in blood glucose level. The pathogenesis of DR includes vascular, neuronal, and inflammatory components leading to activation of complex cellular molecular signaling. If untreated, the disease can culminate in vision loss that eventually leads to blindness. Animal models mimicking different aspects of DM complications have been developed to study the development and progression of DR. Despite the significant contribution of the developed DR models to discovering the mechanisms of DR and the recent achievements in the research field, the sequence of cellular events in diabetic retinas is still under investigation. Partially, this is due to the complexity of molecular mechanisms, although the lack of availability of models that adequately mimic all the neurovascular pathobiological features observed in patients has also contributed to the delay in determining a precise molecular trigger. In this review, we provide an update on the status of animal models of DR to help investigators choose an appropriate system to validate their hypothesis. We also discuss the key cellular and physiological events of DR in these models.

Similar neuronal imprint and no cross-seeded fibrils in \u03b1-synuclein aggregates from MSA and Parkinson\u2019s disease

Aggregated alpha-synuclein (α-syn) is a principal constituent of Lewy bodies (LBs) and glial cytoplasmic inclusions (GCIs) observed respectively inside neurons in Parkinson’s disease (PD) and oligodendrocytes in multiple system atrophy (MSA). Yet, the cellular origin, the pathophysiological role, and the mechanism of formation of these inclusions bodies (IBs) remain to be elucidated. It has recently been proposed that α-syn IBs eventually cause the demise of the host cell by virtue of the cumulative sequestration of partner proteins and organelles. In particular, the hypothesis of a local cross-seeding of other fibrillization-prone proteins like tau or TDP-43 has also been put forward. We submitted sarkosyl-insoluble extracts of post-mortem brain tissue from PD, MSA and control subjects to a comparative proteomic analysis to address these points. Our studies indicate that: (i) α-syn is by far the most enriched protein in PD and MSA extracts compared to controls; (ii) PD and MSA extracts share a striking overlap of their sarkosyl-insoluble proteomes, consisting of a vast majority of mitochondrial and neuronal synaptic proteins, and (iii) other fibrillization-prone protein candidates possibly cross-seeded by α-syn are neither found in PD nor MSA extracts. Thus, our results (i) support the idea that pre-assembled building blocks originating in neurons serve to the formation of GCIs in MSA, (ii) show no sign of amyloid cross-seeding in either synucleinopathy, and (iii) point to the sequestration of mitochondria and of neuronal synaptic components in both LBs and GCIs.

Fault Injection Attacks in Spiking Neural Networks and Countermeasures

Spiking Neural Networks (SNN) are fast emerging as an alternative option to Deep Neural Networks (DNN). They are computationally more powerful and provide higher energy-efficiency than DNNs. While exciting at first glance, SNNs contain security-sensitive assets (e.g., neuron threshold voltage) and vulnerabilities (e.g., sensitivity of classification accuracy to neuron threshold voltage change) that can be exploited by the adversaries. We explore global fault injection attacks using external power supply and laser-induced local power glitches on SNN designed using common analog neurons to corrupt critical training parameters such as spike amplitude and neuron’s membrane threshold potential. We also analyze the impact of power-based attacks on the SNN for digit classification task and observe a worst-case classification accuracy degradation of −85.65%. We explore the impact of various design parameters of SNN (e.g., learning rate, spike trace decay constant, and number of neurons) and identify design choices for robust implementation of SNN. We recover classification accuracy degradation by 30–47% for a subset of power-based attacks by modifying SNN training parameters such as learning rate, trace decay constant, and neurons per layer. We also propose hardware-level defenses, e.g., a robust current driver design that is immune to power-oriented attacks, improved circuit sizing of neuron components to reduce/recover the adversarial accuracy degradation at the cost of negligible area, and 25% power overhead. We also propose a dummy neuron-based detection of voltage fault injection at ∼1% power and area overhead each.

Neurobiology of Neuronal Network Alteration in Intellectual Disability Related to Fetal Alcohol Spectrum Disorders

The molecular and cellular mechanisms by which alcohol produces its deleterious effects on neuronal networks are only now beginning to be understood. This review focused on alcohol-induced neurobiological alterations on neuronal network components underlying information processing, for further understanding of intellectual disability related to FASD. Abnormal neurodevelopmental events related to alcohol-damaged fetal brain included neurogenesis inhibition, aberrant migration, impaired differentiation, exacerbated apoptosis, impaired axon outgrowth and branching altering synaptogenesis and synaptic plasticity, abnormal GABAergic interneurons triggering synaptic inhibitory/excitatory imbalance, reduced myelinogenesis causing injured white matter in prefrontal lobe and atrophied corpus callosum compromising interhemispheric information transfer, the whole compromising neuronal network scaffolding which may lead to biased information processing with deficits in executive function. What added to these abnormalities are smaller gray matter and reduced hippocampus, resulting in cognition and memory failures. As a whole, these developmental disorders may underlie intellectual disability related to FASD. In rodents, these neuronal network components matured mainly during the second and third trimesters equivalents of human gestation. Transferability of results from animal to human was also discussed. It was hoped that the understanding of alcohol-induced neuronal networks failure mechanisms during the developing brain may lay a foundation for prospective new treatments and interventions.

EEGG: An Analytic Brain-Computer Interface Algorithm.

Modeling the brain as a white box is vital for investigating the brain. However, the physical properties of the human brain are unclear. Therefore, BCI algorithms using EEG signals are generally a data-driven approach and generate a black- or gray-box model. This paper presents the first EEG-based BCI algorithm (EEG-BCI using Gang neurons, EEGG) decomposing the brain into some simple components with physical meaning and integrating recognition and analysis of brain activity. Independent and interactive components of neurons or brain regions can fully describe the brain. This paper constructed a relation frame based on the independent and interactive compositions for intention recognition and analysis using a novel dendrite module of Gang neurons. A total of 4,906 EEG data of left- and right-hand motor imagery (MI) from 26 subjects were obtained from GigaDB. Firstly, this paper explored EEGG's classification performance by cross-subject accuracy. Secondly, this paper transformed the trained EEGG model into a relation spectrum expressing independent and interactive components of brain regions. Then, the relation spectrum was verified using the known ERD/ERS phenomenon. Finally, this paper explored the previously unreachable further BCI-based analysis of the brain. (1) EEGG was more robust than typical "CSP+" algorithms for the low-quality data. (2) The relation spectrum showed the known ERD/ERS phenomenon. (3) Interestingly, EEGG showed that interactive components between brain regions suppressed ERD/ERS effects on classification. This means that generating fine hand intention needs more centralized activation in the brain. EEGG decomposed the biological EEG-intention system of this paper into the relation spectrum inheriting the Taylor series (in analogy with the data-driven but human-readable Fourier transform and frequency spectrum), which offers a novel frame for analysis of the brain.

Modelling learning in Caenorhabditis elegans chemosensory and locomotive circuitry for T‐maze navigation

Recently, a new type of Caenorhabditis elegans associative learning was reported, where nematodes learn to reach a target arm in an empty T‐maze, after they have successfully located reward (food) in the same side arm of a similar, baited, training maze. Here, we present a simplified mathematical model of C. elegans chemosensory and locomotive circuitry that replicates C. elegans navigation in a T‐maze and predicts the underlying mechanisms generating maze learning. Based on known neural circuitry, the model circuit responds to food‐released chemical cues by modulating motor neuron activity that drives simulated locomotion. We show that, through modulation of interneuron activity, such a circuit can mediate maze learning by acquiring a turning bias, even after a single training session. Simulated nematode maze navigation during training conditions in food‐baited mazes and during testing conditions in empty mazes is validated by comparing simulated behaviour with new experimental video data, extracted through the implementation of a custom‐made maze tracking algorithm. Our work provides a mathematical framework for investigating the neural mechanisms underlying this novel learning behaviour in C. elegans . Model results predict neuronal components involved in maze and spatial learning and identify target neurons and potential neural mechanisms for future experimental investigations into this learning behaviour.

Early life stress-induced neuroinflammation and neurological disorders: a novel perspective for research.

Early life stress-induced neuroinflammation and neurological disorders: a novel perspective for research.