scholarly journals Deuterated Glutamate-Mediated Neuronal Activity on Micro-Electrode Arrays

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 830
Author(s):  
Wataru Minoshima ◽  
Kyoko Masui ◽  
Tomomi Tani ◽  
Yasunori Nawa ◽  
Satoshi Fujita ◽  
...  
Keyword(s):  
Spontaneous Activity ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Neuronal Networks ◽  
Microelectrode Array ◽  
Mammalian Brain ◽  
Electrode Arrays ◽  
Physiological Properties ◽  
Micro Electrode Arrays

The excitatory synaptic transmission is mediated by glutamate (GLU) in neuronal networks of the mammalian brain. In addition to the synaptic GLU, extra-synaptic GLU is known to modulate the neuronal activity. In neuronal networks, GLU uptake is an important role of neurons and glial cells for lowering the concentration of extracellular GLU and to avoid the excitotoxicity. Monitoring the spatial distribution of intracellular GLU is important to study the uptake of GLU, but the approach has been hampered by the absence of appropriate GLU analogs that report the localization of GLU. Deuterium-labeled glutamate (GLU-D) is a promising tracer for monitoring the intracellular concentration of glutamate, but physiological properties of GLU-D have not been studied. Here we study the effects of extracellular GLU-D for the neuronal activity by using primary cultured rat hippocampal neurons that form neuronal networks on microelectrode array. The frequency of firing in the spontaneous activity of neurons increased with the increasing concentration of extracellular GLU-D. The frequency of synchronized burst activity in neurons increased similarly as we observed in the spontaneous activity. These changes of the neuronal activity with extracellular GLU-D were suppressed by antagonists of glutamate receptors. These results suggest that GLU-D can be used as an analog of GLU with equivalent effects for facilitating the neuronal activity. We anticipate GLU-D developing as a promising analog of GLU for studying the dynamics of glutamate during neuronal activity.

An integrated microfluidic/microelectrode array for the study of activity-dependent intracellular dynamics in neuronal networks

Lab on a Chip ◽  
2018 ◽  
Vol 18 (22) ◽  
pp. 3425-3435 ◽  
Author(s):  
Eve Moutaux ◽  
Benoit Charlot ◽  
Aurélie Genoux ◽  
Frédéric Saudou ◽  
Maxime Cazorla
Keyword(s):  
Neuronal Activity ◽  
Neuronal Networks ◽  
Microelectrode Array ◽  
Activity Dependent

A microfluidics/MEA platform was developed to control neuronal activity while imaging intracellular dynamics within reconstituted neuronal networks.

scholarly journals Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy

2016 ◽  
Vol 371 (1700) ◽  
pp. 20150431 ◽  
Author(s):  
O. Ievglevskyi ◽  
D. Isaev ◽  
O. Netsyk ◽  
A. Romanov ◽  
M. Fedoriuk ◽  
...  
Keyword(s):  
Ion Channels ◽  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Synaptic Activity ◽  
Mammalian Brain ◽  
Strong Increase ◽  
Life And Death ◽  
Acid Sensing Ion Channels

Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca 2+ -permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg 2+ model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus in vivo . Our results reveal a significant novel role for ASICs. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.

scholarly journals Wnt-Frizzled Signaling Regulates Activity-Mediated Synapse Formation

2021 ◽  
Vol 14 ◽  
Author(s):  
Samuel Teo ◽  
Patricia C. Salinas
Keyword(s):  
Wnt Signaling ◽  
Neuronal Activity ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Model Systems ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Wnt Ligands

The formation of synapses is a tightly regulated process that requires the coordinated assembly of the presynaptic and postsynaptic sides. Defects in synaptogenesis during development or in the adult can lead to neurodevelopmental disorders, neurological disorders, and neurodegenerative diseases. In order to develop therapeutic approaches for these neurological conditions, we must first understand the molecular mechanisms that regulate synapse formation. The Wnt family of secreted glycoproteins are key regulators of synapse formation in different model systems from invertebrates to mammals. In this review, we will discuss the role of Wnt signaling in the formation of excitatory synapses in the mammalian brain by focusing on Wnt7a and Wnt5a, two Wnt ligands that play an in vivo role in this process. We will also discuss how changes in neuronal activity modulate the expression and/or release of Wnts, resulting in changes in the localization of surface levels of Frizzled, key Wnt receptors, at the synapse. Thus, changes in neuronal activity influence the magnitude of Wnt signaling, which in turn contributes to activity-mediated synapse formation.

Soft Lithographic Techniques for Guidance of Hippocampal Neurons on Micro-Electrode Arrays

2001 ◽  
pp. 338-341
Author(s):  
Laurent Griscom ◽  
Patrick Degenaar ◽  
Bruno LePioufle ◽  
Eiichi Tamiya ◽  
Hiroyuki Fujita
Keyword(s):  
Hippocampal Neurons ◽  
Electrode Arrays ◽  
Micro Electrode Arrays

scholarly journals Neuronal megalin mediates synaptic plasticity—a novel mechanism underlying intellectual disabilities in megalin gene pathologies

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
João R Gomes ◽  
Andrea Lobo ◽  
Renata Nogueira ◽  
Ana F Terceiro ◽  
Susete Costelha ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Intellectual Disabilities ◽  
Learning And Memory ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Cell Surface Receptor ◽  
Neuronal Cultures

Abstract Donnai-Barrow syndrome, a genetic disorder associated to LRP2 (low-density lipoprotein receptor 2/megalin) mutations, is characterized by unexplained neurological symptoms and intellectual deficits. Megalin is a multifunctional endocytic clearance cell-surface receptor, mostly described in epithelial cells. This receptor is also expressed in the CNS, mainly in neurons, being involved in neurite outgrowth and neuroprotective mechanisms. Yet, the mechanisms involved in the regulation of megalin in the CNS are poorly understood. Using transthyretin knockout mice, a megalin ligand, we found that transthyretin positively regulates neuronal megalin levels in different CNS areas, particularly in the hippocampus. Transthyretin is even able to rescue megalin downregulation in transthyretin knockout hippocampal neuronal cultures, in a positive feedback mechanism via megalin. Importantly, transthyretin activates a regulated intracellular proteolysis mechanism of neuronal megalin, producing an intracellular domain, which is translocated to the nucleus, unveiling megalin C-terminal as a potential transcription factor, able to regulate gene expression. We unveil that neuronal megalin reduction affects physiological neuronal activity, leading to decreased neurite number, length and branching, and increasing neuronal susceptibility to a toxic insult. Finally, we unravel a new unexpected role of megalin in synaptic plasticity, by promoting the formation and maturation of dendritic spines, and contributing for the establishment of active synapses, both in in vitro and in vivo hippocampal neurons. Moreover, these structural and synaptic roles of megalin impact on learning and memory mechanisms, since megalin heterozygous mice show hippocampal-related memory and learning deficits in several behaviour tests. Altogether, we unveil a complete novel role of megalin in the physiological neuronal activity, mainly in synaptic plasticity with impact in learning and memory. Importantly, we contribute to disclose the molecular mechanisms underlying the cognitive and intellectual disabilities related to megalin gene pathologies.

scholarly journals Effects of antiepileptic drugs on hippocampal neurons coupled to micro-electrode arrays

2013 ◽  
Vol 6 ◽  
Author(s):  
Ilaria Colombi ◽  
Sameehan Mahajani ◽  
Monica Frega ◽  
Laura Gasparini ◽  
Michela Chiappalone
Keyword(s):  
Antiepileptic Drugs ◽  
Hippocampal Neurons ◽  
Electrode Arrays ◽  
Micro Electrode Arrays

scholarly journals Application of Spike Sorting Algorithm to Neuronal Signals Originated from Boron Doped Diamond Micro-Electrode Arrays

2020 ◽  
pp. 529-536
Author(s):  
O KLEMPÍŘ ◽  
R KRUPIČKA ◽  
J KRŮŠEK ◽  
I DITTERT ◽  
V PETRÁKOVÁ ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Sorting Algorithm ◽  
Spike Sorting ◽  
Electrode Arrays ◽  
Boron Doped Diamond ◽  
Boron Doped ◽  
Spike Shape ◽  
Custom Made ◽  
Significant Difference ◽  
Micro Electrode Arrays

In this work we report on the implementation of methods for data processing signals from microelectrode arrays (MEA) and the application of these methods for signals originated from two types of MEAs to detect putative neurons and sort them into subpopulations. We recorded electrical signals from firing neurons using titanium nitride (TiN) and boron doped diamond (BDD) MEAs. In previous research, we have shown that these methods have the capacity to detect neurons using commercially-available TiN-MEAs. We have managed to cultivate and record hippocampal neurons for the first time using a newly developed custom-made multichannel BDD-MEA with 20 recording sites. We have analysed the signals with the algorithms developed and employed them to inspect firing bursts and enable spike sorting. We did not observe any significant difference between BDD- and TiN-MEAs over the parameters, which estimated spike shape variability per each detected neuron. This result supports the hypothesis that we have detected real neurons, rather than noise, in the BDD-MEA signal. BDD materials with suitable mechanical, electrical and biocompatibility properties have a large potential in novel therapies for treatments of neural pathologies, such as deep brain stimulation in Parkinson’s disease.

SPONTANEOUS SIGNALLING IN SMALL CENTRAL NEURONS: MECHANISMS AND ROLES OF SPIKE-AMPLITUDE AND SPIKE-INTERVAL FLUCTUATIONS

1996 ◽  
Vol 07 (04) ◽  
pp. 369-376 ◽  
Author(s):  
PETER ÅRHEM ◽  
STAFFAN JOHANSSON
Keyword(s):  
Spontaneous Activity ◽  
Electric Fields ◽  
Hippocampal Neurons ◽  
Brain Activity ◽  
Cortical Network ◽  
Normal Brain ◽  
Brain Physiology ◽  
Random Generators ◽  
The Brain

Spontaneous brain activity is essential for normal brain function. We are studying spontaneous activity in hippocampus at several complexity levels: at the microscopic level by analyzing the role of ion channels, at the mesoscopic level by analyzing the neuronal impulse activity, and at the macroscopic level by computational studies of mean electric fields of cortical network models. We have focused on the role of a subset of hippocampal neurons in the rat — neurons of small size (diameter <10 µ m ). The analysis of spontaneous impulse trains in these neurons, both isolated and in slices, show (i) that impulses vary in amplitude, the magnitude depending on the input signal, suggesting that the amplitude variability may play a role in the information processing of the brain, and (ii) that single ion channel events can trigger neuronal impulses, suggesting that these neurons can function as cellular random generators. The possible role of random generators are investigated by simulating spontaneous activity in a cortical network model, based on a simplified description of the architecture of the CA1 area of hippocampus. The simulations show that such random generators can induce synchronous oscillations in cortical networks. These findings highlight the role of microfluctuations for the global macroactivity of the brain, and stress the importance of the study of channel kinetics for brain physiology.

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