NF1 mutation drives neuronal activity-dependent initiation of optic glioma

Background: Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer’s disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor. Objective: This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain. Methods: ILEI and Aβ levels in the cerebral cortex were monitored using a newly developed ILEI-specific ELISA and in vivo microdialysis in mutant human Aβ precursor protein-knockin mice. ILEI levels in autopsied brains and cerebrospinal fluid (CSF) were measured using ELISA. Results: Extracellular release of ILEI and Aβ was dependent on neuronal activation and specifically on tetanus toxin-sensitive exocytosis of synaptic vesicles. However, simultaneous monitoring of extracellular ILEI and Aβ revealed that a spontaneous fluctuation of ILEI levels appeared to inversely mirror that of Aβ levels. Selective activation and inhibition of synaptic receptors differentially altered these levels. The evoked activation of AMPA-type receptors resulted in opposing changes to ILEI and Aβ levels. Brain ILEI levels were selectively decreased in AD. CSF ILEI concentration correlated with that of Aβ and were reduced in AD and mild cognitive impairment. Conclusion: ILEI and Aβ are released from distinct subpopulations of synaptic terminals in an activity-dependent manner, and ILEI negatively regulates Aβ production in specific synapse types. CSF ILEI might represent a surrogate marker for the accumulation of brain Aβ.

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A Computational Study on Synaptic Plasticity Regulation and Information Processing in Neuron-Astrocyte Networks

Neural Computation ◽

10.1162/neco_a_01399 ◽

2021 ◽

pp. 1-23

Author(s):

Roman Vuillaume ◽

Jhunlyn Lorenzo ◽

Stéphane Binczak ◽

Sabir Jacquir

Keyword(s):

Transfer Function ◽

Neuronal Activity ◽

Information Transfer ◽

Computational Study ◽

Regulation Of Expression ◽

Ionotropic Receptors ◽

Postsynaptic Activity ◽

Outward Currents ◽

Layered Networks ◽

Activity Dependent

Abstract Postsynaptic ionotropic receptors critically shape synaptic currents and underpin their activity-dependent plasticity. In recent years, regulation of expression of these receptors by slow inward and outward currents mediated by gliotransmitter release from astrocytes has come under scrutiny as a potentially important mechanism for the regulation of synaptic information transfer. In this study, we consider a model of astrocyte-regulated synapses to investigate this hypothesis at the level of layered networks of interacting neurons and astrocytes. Our simulations hint that gliotransmission sustains the transfer function across layers, although it decorrelates the neuronal activity from the signal pattern. Overall, our results make clear how astrocytes could transform neuronal activity by inducing a lowfrequency modulation of postsynaptic activity.

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Global sleep homeostasis reflects temporally and spatially integrated local cortical neuronal activity

eLife ◽

10.7554/elife.54148 ◽

2020 ◽

Vol 9 ◽

Author(s):

Christopher W Thomas ◽

Mathilde CC Guillaumin ◽

Laura E McKillop ◽

Peter Achermann ◽

Vladyslav V Vyazovskiy

Keyword(s):

Neuronal Activity ◽

Wave Activity ◽

Neuronal Firing ◽

Daily Amount ◽

Local Process ◽

Sleep Homeostasis ◽

Freely Behaving ◽

Electroencephalogram Eeg ◽

Activity Dependent ◽

Wake State

Sleep homeostasis manifests as a relative constancy of its daily amount and intensity. Theoretical descriptions define ‘Process S’, a variable with dynamics dependent on global sleep-wake history, and reflected in electroencephalogram (EEG) slow wave activity (SWA, 0.5–4 Hz) during sleep. The notion of sleep as a local, activity-dependent process suggests that activity history must be integrated to determine the dynamics of global Process S. Here, we developed novel mathematical models of Process S based on cortical activity recorded in freely behaving mice, describing local Process S as a function of the deviation of neuronal firing rates from a locally defined set-point, independent of global sleep-wake state. Averaging locally derived Processes S and their rate parameters yielded values resembling those obtained from EEG SWA and global vigilance states. We conclude that local Process S dynamics reflects neuronal activity integrated over time, and global Process S reflects local processes integrated over space.

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

Lab on a Chip ◽

10.1039/c8lc00694f ◽

2018 ◽

Vol 18 (22) ◽

pp. 3425-3435 ◽

Cited By ~ 15

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.

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Live-Cell Single-Molecule Imaging with Optogenetics Reveals Dynamics of a Neuronal Activity-Dependent Transcription Factor

Neuromethods - Single Molecule Microscopy in Neurobiology ◽

10.1007/978-1-0716-0532-5_4 ◽

2020 ◽

pp. 59-79

Author(s):

Hironobu Kitagawa ◽

Noriyuki Sugo ◽

Nobuhiko Yamamoto

Keyword(s):

Transcription Factor ◽

Neuronal Activity ◽

Single Molecule ◽

Live Cell ◽

Single Molecule Imaging ◽

Activity Dependent

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Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism

Nature Communications ◽

10.1038/ncomms15132 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 82

Author(s):

Philip Hasel ◽

Owen Dando ◽

Zoeb Jiwaji ◽

Paul Baxter ◽

Alison C. Todd ◽

...

Keyword(s):

Gene Expression ◽

Neuronal Activity ◽

Cortical Neurons ◽

Synaptic Activity ◽

Rna Seq ◽

Metabolic Cooperation ◽

Closely Related Species ◽

Lactate Shuttle ◽

Activity Dependent ◽

Elevated Lactate

Abstract The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte–neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte–neuron metabolic cooperation.

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Neuronal Activity-Dependent Control of Postnatal Neurogenesis and Gliogenesis

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-072116-031054 ◽

2018 ◽

Vol 41 (1) ◽

pp. 139-161 ◽

Cited By ~ 10

Author(s):

Ragnhildur T. Káradóttir ◽

Chay T. Kuo

Keyword(s):

Nervous System ◽

Neuronal Activity ◽

Molecular Mechanisms ◽

Driving Forces ◽

Nervous System Development ◽

Current Evidence ◽

Mammalian Brain ◽

Postnatal Neurogenesis ◽

Proliferation And Differentiation ◽

Activity Dependent

The addition of new neurons and oligodendroglia in the postnatal and adult mammalian brain presents distinct forms of gray and white matter plasticity. Substantial effort has been devoted to understanding the cellular and molecular mechanisms controlling postnatal neurogenesis and gliogenesis, revealing important parallels to principles governing the embryonic stages. While during central nervous system development, scripted temporal and spatial patterns of neural and glial progenitor proliferation and differentiation are necessary to create the nervous system architecture, it remains unclear what driving forces maintain and sustain postnatal neural stem cell (NSC) and oligodendrocyte progenitor cell (OPC) production of new neurons and glia. In recent years, neuronal activity has been identified as an important modulator of these processes. Using the distinct properties of neurotransmitter ionotropic and metabotropic channels to signal downstream cellular events, NSCs and OPCs share common features in their readout of neuronal activity patterns. Here we review the current evidence for neuronal activity-dependent control of NSC/OPC proliferation and differentiation in the postnatal brain, highlight some potential mechanisms used by the two progenitor populations, and discuss future studies that might advance these research areas further.

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