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At least 109 records · Page 6

Neurochemical, morphologic, and laminar characterization of cortical projection neurons in the cingulate motor areas of the macaque monkey

The primate cingulate gyrus contains multiple cortical areas that can be distinguished by several neurochemical features, including the distribution of neurofilament protein-enriched pyramidal neurons. In addition, connectivity and functional properties indicate that there are multiple motor areas in the cortex lining the cingulate sulcus. These motor areas were targeted for analysis of potential interactions among regional specialization, connectivity, and cellular characteristics such as neurochemical profile and morphology. Specifically, intracortical injections of retrogradely transported dyes and intracellular injection were combined with immunocytochemistry to investigate neurons projecting from the cingulate motor areas to the putative forelimb region of the primary motor cortex, area M1. Two separate groups of neurons projecting to area M1 emanated from the cingulate sulcus, one anterior and one posterior, both of which furnished commissural and ipsilateral connections with area M1. The primary difference between the two populations was laminar origin, with the anterior projection originating largely in deep layers, and the posterior projection taking origin equally in superficial and deep layers. With regard to cellular morphology, the anterior projection exhibited more morphologic diversity than the posterior projection. Commissural projections from both anterior and posterior fields originated largely in layer VI. Neurofilament protein distribution was a reliable tool for localizing the two projections and for discriminating between them. Comparable proportions of the two sets of projection neurons contained neurofilament protein, although the density and distribution of the total population of neurofilament protein-enriched neurons was very different in the two subareas of origin. Within a projection, the participating neurons exhibited a high degree of morphologic heterogeneity, and no correlation was observed between somatodendritic morphology and neurofilament protein content. Thus, although the neurons that provide the anterior and posterior cingulate motor projections to area M1 differ morphologically and in laminar origin, their neurochemical profiles are similar with respect to neurofilament protein. This suggests that neurochemical phenotype may be a more important unifying feature for corticocortical projections than morphology.

NASA Discipline Neuroscience↗

A model for the characterization of the spatial properties in vestibular neurons

Quantitative study of the static and dynamic response properties of some otolith-sensitive neurons has been difficult in the past partly because their responses to different linear acceleration vectors exhibited no "null" plane and a dependence of phase on stimulus orientation. The theoretical formulation of the response ellipse provides a quantitative way to estimate the spatio-temporal properties of such neurons. Its semi-major axis gives the direction of the polarization vector (i.e., direction of maximal sensitivity) and it estimates the neuronal response for stimulation along that direction. In addition, the semi-minor axis of the ellipse provides an estimate of the neuron's maximal sensitivity in the "null" plane. In this paper, extracellular recordings from otolith-sensitive vestibular nuclei neurons in decerebrate rats were used to demonstrate the practical application of the method. The experimentally observed gain and phase dependence on the orientation angle of the acceleration vector in a head-horizontal plane was described and satisfactorily fit by the response ellipse model. In addition, the model satisfactorily fits neuronal responses in three-dimensions and unequivocally demonstrates that the response ellipse formulation is the general approach to describe quantitatively the spatial properties of vestibular neurons.

Non-NASA Center↗

In-vivo neuronal dysfunction by Aβ and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer’s disease

The molecular mechanisms underlying neuronal dysfunction in Alzheimer’s disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aβ and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant’s real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aβ-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aβ and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aβ and tau’s synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aβ-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.

60 APPLIED LIFE SCIENCES↗

Visualization of local phosphatidylcholine synthesis within hippocampal neurons using a compartmentalized culture system and imaging mass spectrometry

Highlights: • A compartmentalized neuron culture system was combined with imaging mass spectrometry. • Phosphatidylcholine (PC) species within rat hippocampal neurons were visualized. • Differential synthetic activity of a PC species within neurons was observed. • Neurites synthesized a PC species using local extracellular free fatty acids in situ. Neurons extend neurites with an increased synthesis of phosphatidylcholine (PC) that is not only a membrane component but also a functional regulator with specific fatty acid composition. To analyze the local synthesis of the PC molecular species within neurons, we combined a compartmentalized culture system with matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). We observed that a newly synthesized PC, which contains exogenously administered palmitic acid-d{sub 3}, is accumulated at the cell bodies and the tips of the distal neurites. The local accumulation within distal neurites is formed by distinct metabolic activity from cell bodies, suggesting that the local extracellular composition of free fatty acid can be a key to regulate specific functions of each PC molecular species. We expect our simple method to be a starting point for more sophisticated in vitro analytical methods for unveiling detailed lipid metabolisms within neurons.

60 APPLIED LIFE SCIENCES↗

Alteration of global protein SUMOylation in neurons and astrocytes in response to Alzheimer's disease-associated insults

Highlights: • The protein SUMOylation was not altered in the plaque-bearing AD model mouse brain. • Oxidative/excitotoxic stimuli reduced the SUMO1-modified protein levels in neurons. • SUMOylation prominently altered by cytotoxic stimuli in neurons than in astrocytes. SUMOylation, a post-translational modification of lysine residues by small ubiquitin-like modifier (SUMO) proteins, has been implicated in the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD), and in neuron- and astrocyte-specific physiological functions. Global SUMOylation is increased in the AD mouse brain in the pre-plaque-forming stage but returns to wild-type levels in the plaque-bearing stage. To clarify the reason for the transient change in SUMOylation, we analyzed the alteration of global SUMOylation induced by AD-associated cytotoxic stimuli in neurons and astrocytes individually. In neurons, amyloid β42 oligomers induced some but not significant increase in levels of SUMO1-modified proteins. Both hydrogen peroxide and glutamate significantly reduced SUMO1-modified protein levels. These changes were more prominent in neurons than in astrocytes. The opposite effect of Aβ and oxidative/excitotoxic stimuli on SUMO1 modification may cause the pathological stage-associated change in the level of SUMO-modified proteins in the AD mouse brain.

60 APPLIED LIFE SCIENCES↗

Detection of the receptor for advanced glycation endproducts in neuronally-derived exosomes in plasma

Highlights: • RAGE is present in plasma exosomes. • RAGE is present in neuronally-derived exosomes in plasma. • Exosomal RAGE is weakly to moderately associated with age, BMI, and cognition. • Higher total protein content in plasma exosomes is associated with worse cognition. Exosomes are nanovesicles that participate in cell-to-cell communication and are secreted by a variety of cells including neurons. Recent studies suggest that neuronally-derived exosomes are detectable in plasma and that their contents likely reflect expression of various biomarkers in brain tissues. The receptor for advanced glycation endproducts (RAGE) has been implicated in the pathophysiology of Alzheimer's disease (AD) and is increased in brain regions affected by AD. The goal of our project was to determine whether RAGE is present in plasma exosomes, and specifically exosomes derived from neurons. Exosomes were isolated from plasma samples (n = 8) by precipitation (ExoQuick) and ultracentrifugation methods. Neuronally-derived exosomes were isolated using a biotin-tagged L1 Cell Adhesion Molecule (L1CAM) specific antibody and streptavidin-tagged agarose resin. RAGE expression was measured by Western blots and ELISA. Western Blotting showed that RAGE is present in L1CAM-positive exosomes isolated using both methods. Mean (SD) exosomal RAGE levels were 164 (60) pg/ml by ExoQuick and were highly correlated with plasma sRAGE levels (r = 0.87, p = 0.005), which were approximately 7.5-fold higher than exosomal levels. Weak to moderate correlations were found between exosomal RAGE and age, BMI, and cognitive function. These results show for the first time that RAGE is present in neuronally-derived plasma exosomes, and suggest that exosomal RAGE may be a novel biomarker that reflects pathophysiological processes in the brain.

60 APPLIED LIFE SCIENCES↗

Activation of galanin receptor 1 inhibits locus coeruleus neurons via GIRK channels

The noradrenergic neurons of the locus coeruleus (LC) are associated with various brain functions and psychiatric disorders, such as addiction and depression. It has been shown that neuropeptide galanin (GAL) inhibits neuronal excitability in LC, but the mechanisms remain unclear. In the present study, we investigated the ionic and signal transduction mechanisms underlying inhibitory effect of GAL on LC neurons using whole-cell patch clamp recording in rat brain slices. Bath application of GAL decreased the spontaneous firings and induced a dose-dependent hyperpolarization of LC neurons and this effect was attenuated by knockdown of Galr1, but not Galr2, confirming that mainly GALR1 mediates the inhibition effect of GAL. The inhibitory effect of GAL was also blocked by treatments of pertussis toxin (PTX), GTP-γ-s or GDP-β-s, respectively, indicating that the functions of PTX sensitive G{sub i/o} protein are required for GAL-induced hyperpolarization. Moreover, the blockers of GIRK (tertiapin-Q or SCH2 3390 hydrochloride) attenuated the GAL response while blocker of BK/SK/K{sub ATP} channels or TASK-1/3 channels did not affect it significantly, suggesting that GIRK channels play an important role in GAL-induced hyperpolarization in LC neurons. Taken together, the inhibitory effect of GAL on LC neurons is mediated by GALR1 via PTX-sensitive G{sub i/o} proteins, which activate GIRK channels.

60 APPLIED LIFE SCIENCES↗

MicroRNA-98-5p ameliorates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury by inhibiting Bach1 and promoting Nrf2/ARE signaling

Highlights: • miR-98 expression was altered in neurons with OGD/R treatment. • miR-98-5p inhibited OGD/R-induced apoptosis and ROS production. • miR-98-5p targets and regulates Bach1. • miR-98-5p regulates OGD/R-induced injury by targeting Bach1. • miR-98-5p regulates Nrf2/ARE signaling by targeting Bach1. MicroRNA-98-5p (miR-98-5p) is a stress-related microRNA (miRNA) that plays an important role in regulating cell survival, apoptosis, and oxidative stress in multiple cell types and diseases. However, little is known about the role of miR-98-5p in cerebral ischemia/reperfusion injury. In this study, we investigated the role and mechanism of miR-98-5p in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R), an in vitro model of cerebral ischemia/reperfusion injury. We found that miR-98 expression was significantly altered in neurons in response to OGD/R treatment. Functional experiments showed that overexpression of miR-98-5p inhibited OGD/R-induced apoptosis and reactive oxygen species (ROS) production in neurons, whereas inhibition of miR-98-5p showed the opposite effect. Interestingly, bioinformatics analysis predicted that BTB and CNC homology 1 (Bach1) was a potential target gene of miR-98-5p, that was verified by dual-luciferase reporter assay. Moreover, overexpression of miR-98-5p inhibited Bach1 expression while suppression of miR-98-5p promoted Bach1 expression in neurons. Notably, miR-98-5p was shown to regulate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the activity of the antioxidant response element (ARE). However, overexpression of Bach1 or silencing of Nrf2 significantly abolished the miR-98-5p-mediated neuroprotective effect. Overall, these results demonstrate that miR-98-5p ameliorates OGD/R-induced neuronal injury in vitro through targeting to promote activation of Nrf2/ARE signaling. Our study suggests that miR-98-5p may play a potential role in cerebral ischemia/reperfusion injury and represents a potential therapeutic target for neuroprotection.

60 APPLIED LIFE SCIENCES↗

Dedifferentiation of Neurons Precedes Tumor Formation in lola Mutants

The ability to reprogram differentiated cells into a pluripotent state has revealed that the differentiated state is plastic and reversible. It is evident, therefore, that mechanisms must be in place to maintain cells in a differentiated state. Transcription factors that specify neuronal characteristics have been well studied, but less is known about the mechanisms that prevent neurons from dedifferentiating to a multipotent, stem cell-like state. Here, we identify Lola as a transcription factor that is required to maintain neurons in a differentiated state. We show that Lola represses neural stem cell genes and cell-cycle genes in postmitotic neurons. In lola mutants, neurons dedifferentiate, turn on neural stem cell genes, and begin to divide, forming tumors. Thus, neurons rather than stem cells or intermediate progenitors are the tumor-initiating cells in lola mutants.

59 BASIC BIOLOGICAL SCIENCES↗

Diazinon and diazoxon impair the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons

Evidence from in vivo and epidemiological studies suggests that organophosphorus insecticides (OPs) are developmental neurotoxicants, but possible underlying mechanisms are still unclear. Astrocytes are increasingly recognized for their active role in normal neuronal development. This study sought to investigate whether the widely-used OP diazinon (DZ), and its oxygen metabolite diazoxon (DZO), would affect glial–neuronal interactions as a potential mechanism of developmental neurotoxicity. Specifically, we investigated the effects of DZ and DZO on the ability of astrocytes to foster neurite outgrowth in primary hippocampal neurons. The results show that both DZ and DZO adversely affect astrocyte function, resulting in inhibited neurite outgrowth in hippocampal neurons. This effect appears to be mediated by oxidative stress, as indicated by OP-induced increased reactive oxygen species production in astrocytes and prevention of neurite outgrowth inhibition by antioxidants. The concentrations of OPs were devoid of cytotoxicity, and cause limited acetylcholinesterase inhibition in astrocytes (18 and 25% for DZ and DZO, respectively). Among astrocytic neuritogenic factors, the most important one is the extracellular matrix protein fibronectin. DZ and DZO decreased levels of fibronectin in astrocytes, and this effect was also attenuated by antioxidants. Underscoring the importance of fibronectin in this context, adding exogenous fibronectin to the co-culture system successfully prevented inhibition of neurite outgrowth caused by DZ and DZO. These results indicate that DZ and DZO increase oxidative stress in astrocytes, and this in turn modulates astrocytic fibronectin, leading to impaired neurite outgrowth in hippocampal neurons. - Highlights: • DZ and DZO inhibit astrocyte-mediated neurite outgrowth in rat hippocampal neurons. • Oxidative stress is involved in inhibition of neuritogenesis by DZ and DZO. • DZ and DZO decrease expression of the neuritogenic factor fibronectin in astrocytes. • Exogenous fibronectin antagonizes the effect of DZ and DZO on neuritogenesis.

60 APPLIED LIFE SCIENCES↗

Development of a pluripotent stem cell derived neuronal model to identify chemically induced pathway perturbations in relation to neurotoxicity: Effects of CREB pathway inhibition

According to the advocated paradigm shift in toxicology, acquisition of knowledge on the mechanisms underlying the toxicity of chemicals, such as perturbations of biological pathways, is of primary interest. Pluripotent stem cells (PSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), offer a unique opportunity to derive physiologically relevant human cell types to measure molecular and cellular effects of such pathway modulations. Here we compared the neuronal differentiation propensity of hESCs and hiPSCs with the aim to develop novel hiPSC-based tools for measuring pathway perturbation in relation to molecular and cellular effects in vitro. Among other fundamental pathways, also, the cAMP responsive element binding protein (CREB) pathway was activated in our neuronal models and gave us the opportunity to study time-dependent effects elicited by chemical perturbations of the CREB pathway in relation to cellular effects. We show that the inhibition of the CREB pathway, using 2-naphthol-AS-E-phosphate (KG-501), induced an inhibition of neurite outgrowth and synaptogenesis, as well as a decrease of MAP2{sup +} neuronal cells. These data indicate that a CREB pathway inhibition can be related to molecular and cellular effects that may be relevant for neurotoxicity testing, and, thus, qualify the use of our hiPSC-derived neuronal model for studying chemical-induced neurotoxicity resulting from pathway perturbations. - Highlights: • HESCs derived neuronal cells serve as benchmark for iPSC based neuronal toxicity test development. • Comparisons between hESCs and hiPSCs demonstrated variability of the epigenetic state • CREB pathway modulation have been explored in relation to the neurotoxicant exposure KG-501 • hiPSC might be promising tools to translate theoretical AoPs into toxicological in vitro tests.

60 APPLIED LIFE SCIENCES↗

Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death

Resveratrol (3,5,4′-trihydroxystilbene) (RSV), a polyphenol widely present in plants, exerts a neuroprotective function in several neurological conditions; it is an activator of class III histone deacetylase sirtuin1 (SIRT1), a crucial regulator in the pathophysiology of neurodegenerative diseases. By contrast, the RE1-silencing transcription factor (REST) is involved in the neurotoxic effects following exposure to polychlorinated biphenyl (PCB) mixture A1254. The present study investigated the effects of RSV-induced activation of SIRT1 on REST expression in SH-SY5Y cells. Further, we investigated the possible relationship between the non-dioxin-like (NDL) PCB-95 and REST through SIRT1 to regulate neuronal death in rat cortical neurons. Our results revealed that RSV significantly decreased REST gene and protein levels in a dose- and time-dependent manner. Interestingly, overexpression of SIRT1 reduced REST expression, whereas EX-527, an inhibitor of SIRT1, increased REST expression and blocked RSV-induced REST downregulation. These results suggest that RSV downregulates REST through SIRT1. In addition, RSV enhanced activator protein 1 (AP-1) transcription factor c-Jun expression and its binding to the REST promoter gene. Indeed, c-Jun knockdown reverted RSV-induced REST downregulation. Intriguingly, in SH-SY5Y cells and rat cortical neurons the NDL PCB-95 induced necrotic cell death in a concentration-dependent manner by increasing REST mRNA and protein expression. In addition, SIRT1 knockdown blocked RSV-induced neuroprotection in rat cortical neurons treated with PCB-95. Collectively, these results indicate that RSV via SIRT1 activates c-Jun, thereby reducing REST expression in SH-SY5Y cells under physiological conditions and blocks PCB-95-induced neuronal cell death by activating the same SIRT1/c-Jun/REST pathway. - Highlights: • Resveratrol via SIRT1/c-Jun downregulates REST mRNA and protein in SH-SY5Y cells. • Non-dioxin-like (NDL) PCB-95 is cytotoxic to SH-SY5Y cells and cortical neurons. • PCB-95-induced cytotoxicity is mediated by REST. • PCB-95-induced cell death is inhibited by resveratrol.

60 APPLIED LIFE SCIENCES↗

Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro. • Totarol activates PI3K/Akt pathway in neurons. • Totarol induces HO-1, GSH and SOD expression in vitro and in vivo. • Totarol exhibits neuroprotective effects in rat brain ischemic stroke model.

60 APPLIED LIFE SCIENCES↗

iPSC-derived neurons profiling reveals GABAergic circuit disruption and acetylated α-tubulin defect which improves after iHDAC6 treatment in Rett syndrome

Highlights: • Development of a patient-specific neuronal model for Rett syndrome using iPSCs. • GABAergic circuits up-regulation in Rett iPSC-derived neurons. • Reduction of acetylated α-tubulin in Rett neurons, reverted by selective HDAC6 inhibitors. Mutations in MECP2 gene have been identified in more than 95% of patients with classic Rett syndrome, one of the most common neurodevelopmental disorders in females. Taking advantage of the breakthrough technology of genetic reprogramming, we investigated transcriptome changes in neurons differentiated from induced Pluripotent Stem Cells (iPSCs) derived from patients with different mutations. Profiling by RNA-seq in terminally differentiated neurons revealed a prominent GABAergic circuit disruption along with a perturbation of cytoskeleton dynamics. In particular, in mutated neurons we identified a significant decrease of acetylated α-tubulin which can be reverted by treatment with selective inhibitors of HDAC6, the main α-tubulin deacetylase. These findings contribute to shed light on Rett pathogenic mechanisms and provide hints for the treatment of Rett-associated epileptic behavior as well as for the definition of new therapeutic strategies for Rett syndrome.

60 APPLIED LIFE SCIENCES↗

NMDA receptors inhibit axonal outgrowth by inactivating Akt and activating GSK-3β via calcineurin in cultured immature hippocampal neurons

Highlights: • Inhibition of NMDA promoted axonal outgrowth at the early stages. • GluN2B but not GluN2A inhibited axonal outgrowth in immature hippocampal neurons. • NMDA inhibited axonal outgrowth by inactivating Akt and activating GSK-3β signaling. Neurons are highly polarized cells with an axon and dendritic arbors. It is still not well studied that how formation and elaboration of axon and dendrites is controlled by diffusible signaling factors such as glutamate via specific receptors. We found that N-methyl-D-aspartate (NMDA) receptors were enriched (stage 2–3) but decreased expression (stage 4–5) at tip of axon of cultured hippocampal neurons during distinct development stages. Inhibition of NMDA receptor activity by competitive antagonist DL-2-amino-5-phosphonovalerate (APV) or channel blocker MK801 promoted axonal outgrowth at the early stages, whereas inhibited dendritic development in later stages. Meanwhile, knockdown of NMDA receptors also promoted axonal outgrowth and branch in immature neurons. Furthermore, GluN2B but not GluN2A subunit inhibited axonal outgrowth in immature hippocampal neurons. Finally, we found that NMDA receptors inhibited axonal outgrowth by inactivating Akt and activating GSK-3β signaling in a calcineurin-dependent manner. Taken together, our results demonstrate that stabilization GSK-3β activation in the axon growth cone by Ca{sup 2+} influx through NMDA receptors may be involved in regulation of axon formation in immature neurons at early stages.

60 APPLIED LIFE SCIENCES↗

A chimeric path to neuronal synchronization

Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Synchronization properties of coupled chaotic neurons: The role of random shared input

Spike-time correlations of neighbouring neurons depend on their intrinsic firing properties as well as on the inputs they share. Studies have shown that periodically firing neurons, when subjected to random shared input, exhibit asynchronicity. Here, we study the effect of random shared input on the synchronization of weakly coupled chaotic neurons. The cases of so-called electrical and chemical coupling are both considered, and we observe a wide range of synchronization behaviour. When subjected to identical shared random input, there is a decrease in the threshold coupling strength needed for chaotic neurons to synchronize in-phase. The system also supports lag–synchronous states, and for these, we find that shared input can cause desynchronization. We carry out a master stability function analysis for a network of such neurons and show agreement with the numerical simulations. The contrasting role of shared random input for complete and lag synchronized neurons is useful in understanding spike-time correlations observed in many areas of the brain.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Spiral waves in externally excited neuronal network: Solvable model with a monotonically differentiable magnetic flux

Spiral waves are particular spatiotemporal patterns connected to specific phase singularities representing topological wave dislocations or nodes of zero amplitude, witnessed in a wide range of complex systems such as neuronal networks. The appearance of these waves is linked to the network structure as well as the diffusion dynamics of its blocks. We report a novel form of the Hindmarsh-Rose neuron model utilized as a square neuronal network, showing the remarkable multistructure of dynamical patterns ranging from characteristic spiral wave domains of spatiotemporal phase coherence to regions of hyperchaos. The proposed model comprises a hyperbolic memductance function as the monotone differentiable magnetic flux. Hindmarsh-Rose neurons with an external electromagnetic excitation are considered in three different cases: no excitation, periodic excitation, and quasiperiodic excitation. We performed an extensive study of the neuronal dynamics including calculation of equilibrium points, bifurcation analysis, and Lyapunov spectrum. We have found the property of antimonotonicity in bifurcation scenarios with no excitation or periodic excitation and identified wide regions of hyperchaos in the case of quasiperiodic excitation. Furthermore, the formation and elimination of the spiral waves in each case of external excitation with respect to stimuli parameters are investigated. We have identified novel forms of Hindmarsh-Rose bursting dynamics. Our findings reveal multipartite spiral wave formations and symmetry breaking spatiotemporal dynamics of the neuronal model that may find broad practical applications. © 2019 Author(s).

60 APPLIED LIFE SCIENCES↗