Dopamine depletion alters neuroplasticity-related signaling in the rat hippocampus

Animal Cells and Systems, Journal Year: 2023, Volume and Issue: 27(1), P. 436 - 446

Published: Dec. 11, 2023

Dopamine (DA) plays a significant role in regulating hippocampal function, particularly modulating synaptic plasticity. Despite this, comprehensive understanding of the molecular mechanisms involved neuroplasticity-related signaling influenced by DA remains incomplete. This study aimed to elucidate changes expression key molecules related neuroplasticity following depletion rats. To induce depletion, unilateral striatal infusions 6-hydroxydopamine (6-OHDA) were administered adult Sprague-Dawley The subsequent loss nigrostriatal DAergic these 6-OHDA-lesioned rats was confirmed using an apomorphine-induced rotation test at 4 weeks post-infusion and assessing levels tyrosine hydroxylase (TH) through immunohistochemistry western blotting 7 post-infusion. A decrease signaling, evidenced reduced TH-positive immunoreactivity, also noted ipsilateral hippocampus lesioned Interestingly, 6-OHDA infusion led increased phosphorylation pivotal plasticity-related proteins, including extracellular signal-regulated kinase (ERK), protein B (Akt), glycogen synthase 3β (GSK3β), cAMP response element-binding (CREB), infusion. extend findings, vitro experiments conducted on primary neurons exposed and/or active D1/D2 receptor antagonist, flupentixol (Flux). inhibited constitutive ERK, Akt, GSK3, CREB, while Flux restored levels. Taken together, findings indicate that triggers increase hippocampus, suggesting possible compensatory mechanism promotes activity-independent depletion.

Language: Английский

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Device Engineering of Dual Metal Gate-Based Artificial Synapse for Enhanced Plasticity Utilizing Al₂O₃-Based Ion Conducting Electrolyte

IEEE Transactions on Electron Devices, Journal Year: 2024, Volume and Issue: 71(4), P. 2749 - 2754

Published: Feb. 26, 2024

An energy-efficient artificial neuron can be developed with synaptic transistors using the electric double-layer (EDL) effect in transistor's oxide layer. This work proposes a dual metal gate (DMG) engineered indium-gallium-zinc-oxide (IGZO) transistor utilizing novel Al2O3-based ion conducting electrolyte for tunable performance based on drift-diffusion model. The simulation has been carried out at an ultralow voltage of 0.5 V employing two connection schemes. results show accurate simulations activities like paired-pulse facilitation, excitatory postsynaptic current (EPSC), memory transition from short-term to long-term, depression, and dynamic filtering characteristics. To validate device's performance, voltage, frequency, pulse interval modulation have determine strength device. assists higher ON/OFF ratio, leading more robust potentiation depression imply that DMG-based EDL device proposed provides physical understanding helps relate biological neuron.

Language: Английский

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Delay-dependent transitions of phase synchronization and coupling symmetry between neurons shaped by spike-timing-dependent plasticity

Cognitive Neurodynamics, Journal Year: 2022, Volume and Issue: 17(2), P. 523 - 536

Published: July 23, 2022

Language: Английский

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Efficient suppression of parkinsonian beta oscillations in a closed-loop model of deep brain stimulation with amplitude modulation

Frontiers in Human Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Jan. 26, 2023

Introduction Parkinson's disease (PD) is a movement disorder characterized by the pathological beta band (15–30 Hz) neural oscillations within basal ganglia (BG). It shown that suppression of abnormal correlated with improvement PD motor symptoms, which goal standard therapies including deep brain stimulation (DBS). To overcome stimulation-induced side effects and inefficiencies conventional DBS (cDBS) to reduce administered current, closed-loop adaptive (aDBS) techniques were developed. In this method, frequency and/or amplitude are modulated based on various biomarkers. Methods Here, computational modeling cortico-BG-thalamic network in normal conditions, we show aDBS subthalamic nucleus (STN) modulation leads more effective parkinsonian BG. Results Our results restored their range reliability response thalamic neurons cortex commands retained due modulation. Furthermore, notably less current during compared cDBS control STN local field potential (LFP) activity. Discussion Efficient models may contribute clinical development optimized designed patients while leading better therapeutic outcome.

Language: Английский

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Dynamic networks of cortico-muscular interactions in sleep and neurodegenerative disorders

Frontiers in Network Physiology, Journal Year: 2023, Volume and Issue: 3

Published: Sept. 5, 2023

The brain plays central role in regulating physiological systems, including the skeleto-muscular and locomotor system. Studies of cortico-muscular coordination have primarily focused on associations between movement tasks dynamics specific waves. However, brain-muscle functional networks synchronous among waves muscle activity rhythms that underlie control remain unknown. Here we address following fundamental questions: what are structure networks; whether main network mediators control; how hierarchical organization relates to distinct states under autonomic regulation such as wake, sleep, sleep stages; altered with neurodegenerative disorders. We study interactions all physiologically relevant across cortical locations leg chin healthy Parkinson's disease (PD) subjects. Utilizing Network Physiology framework time delay stability approach, find 1) each state is characterized by a unique profile links strength; 2) particular play during state; 3) PD leads muscle-specific breakdown networks, altering sleep-stage stratification pattern connectivity strength. In subjects exhibit pronounced stronger wake light weaker REM deep sleep. contrast, reorganize decline strength non-REM increase REM, leading markedly different gradual from Further, stages profiles, which PD, indicating disruption communication rhythms. Our findings demonstrate presence previously unrecognized basic principles locomotion, potential clinical implications for novel network-based biomarkers early detection disorders, movement,

Language: Английский

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Synaptic reshaping of plastic neuronal networks by periodic multichannel stimulation with single-pulse and burst stimuli

PLoS Computational Biology, Journal Year: 2022, Volume and Issue: 18(11), P. e1010568 - e1010568

Published: Nov. 3, 2022

Synaptic dysfunction is associated with several brain disorders, including Alzheimer's disease, Parkinson's disease (PD) and obsessive compulsive disorder (OCD). Utilizing synaptic plasticity, stimulation capable of reshaping connectivity. This may pave the way for novel therapies that specifically counteract pathological For instance, in PD, multichannel coordinated reset (CRS) was designed to neuronal synchrony down-regulate CRS shown entail long-lasting therapeutic aftereffects PD patients related animal models. marked contrast conventional deep (DBS) therapy, where symptoms return shortly after ceases. In present paper, we study by periodic (PMCS) networks leaky integrate-and-fire (LIF) neurons spike-timing-dependent plasticity (STDP). During PMCS, phase-shifted stimulus trains are delivered segregated subpopulations. Harnessing STDP, PMCS leads changes network structure. We found PMCS-induced structure depend on both phase lags between stimuli shape individual stimuli. Single-pulse burst low intraburst frequency synapses receiving simultaneously. contrast, high up-regulate these synapses. derive theoretical approximations stimulation-induced enables us formulate strategies inducing a variety structures. Our results provide testable hypotheses future pre-clinical clinical studies suggest be suitable plastic Furthermore, insight how type affect outcome DBS. strongly impact parameter adjustment procedures DBS, which, so far, primarily focused acute effects stimulation.

Language: Английский

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Feedback control of collective dynamics in an oscillator population with time-dependent connectivity

Frontiers in Network Physiology, Journal Year: 2024, Volume and Issue: 4

Published: Feb. 2, 2024

We present a numerical study of pulsatile feedback-based control synchrony level in highly-interconnected oscillatory network. focus on nontrivial case when the system is close to synchronization transition point and exhibits collective rhythm with strong amplitude modulation. pay special attention technical but essential steps like causal real-time extraction signal interest from noisy measurement estimation instantaneous phase amplitude. The feedback loop’s parameters are tuned automatically suppress synchrony. Though motivated by neuroscience, results relevant controlling activity ensembles various natures and, thus, rapidly developing field network physiology.

Language: Английский

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Dynamics of parkinsonian oscillations mediated by transmission delays in a mean-field model of the basal ganglia

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 14, 2024

Neural interactions in the brain are affected by transmission delays which may critically alter signal propagation across different regions both normal and pathological conditions. The effect of interaction on dynamics generic neural networks has been extensively studied theoretical computational models. However, role development oscillatory basal ganglia (BG) Parkinson's disease (PD) is overlooked.

Language: Английский

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The onset of motor learning impairments in Parkinson’s disease: a computational investigation

Brain Informatics, Journal Year: 2024, Volume and Issue: 11(1)

Published: Jan. 29, 2024

The basal ganglia (BG) is part of a basic feedback circuit regulating cortical function, such as voluntary movements control, via their influence on thalamocortical projections. BG disorders, namely Parkinson's disease (PD), characterized by the loss neurons in substantia nigra, involve progressive motor functions. At present, PD incurable. Converging evidences suggest onset PD-specific pathology prior to appearance classical signs. This latent phase neurodegeneration particular relevance developing more effective therapies intervening at earliest stages disease. Therefore, key challenge research identify and validate markers for preclinical prodromal illness. We propose mechanistic neurocomputational model mesoscopic scale investigate behavior simulated neural system after several degrees lesion with aim possibly evaluating which smallest compromising learning. In other words, we developed working framework analysis theoretical early-stage PD. While simulations healthy conditions confirm role dopamine learning, pathological network predicts that there may exist abnormalities learning process, physiological alterations BG, do not yet presence symptoms typical clinical diagnosis.

Language: Английский

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Coordinated reset stimulation of plastic neural networks with spatially dependent synaptic connections

Frontiers in Network Physiology, Journal Year: 2024, Volume and Issue: 4

Published: May 28, 2024

Abnormal neuronal synchrony is associated with several neurological disorders, including Parkinson's disease (PD), essential tremor, dystonia, and epilepsy. Coordinated reset (CR) stimulation was developed computationally to counteract abnormal synchrony. During CR stimulation, phase-shifted stimuli are delivered multiple sites. Computational studies in plastic neural networks reported that drove the into an attractor of a stable desynchronized state by down-regulating synaptic connections, which led long-lasting desynchronization effects outlasted stimulation. Later, corresponding therapeutic were found animal models PD patients. To date, it unclear how spatially dependent as typically observed brain, shape CR-induced downregulation effects.

Language: Английский

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