scholarly journals Fine-tuning activity-dependent bulk endocytosis via kinases and phosphatases

2021 ◽  
Vol 220 (12) ◽  
Author(s):  
Ira Milosevic ◽  
Michael A. Cousin
Keyword(s):  
Molecular Mechanism ◽  
Neuronal Activity ◽  
Dominant Mode ◽  
Fine Tuning ◽  
Regulation Of Activity ◽  
Synaptojanin 1 ◽  
Activity Dependent

The regulation of activity-dependent bulk endocytosis, the dominant mode of membrane retrieval in response to intense neuronal activity, is poorly understood. In this JCB issue, Peng et al. (2021. J. Cell. Biol.https://doi.org/10.1083/jcb.202011028) propose a novel molecular mechanism for the coordination of activity-dependent bulk endocytosis that builds on Minibrain kinase and its presynaptic substrate synaptojanin-1.

scholarly journals Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome

2018 ◽  
Vol 115 (23) ◽  
pp. E5363-E5372 ◽  
Author(s):  
Sivan Osenberg ◽  
Ariel Karten ◽  
Jialin Sun ◽  
Jin Li ◽  
Shaun Charkowick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Mouse Model ◽  
Rett Syndrome ◽  
Neuronal Activity ◽  
Intron Retention ◽  
Neurodevelopmental Disorder ◽  
Fine Tuning ◽  
Global Pattern ◽  
Activity Dependent

Rett syndrome (RTT) is a severe neurodevelopmental disorder that affects about 1 in 10,000 female live births. The underlying cause of RTT is mutations in the X-linked gene, methyl-CpG-binding protein 2 (MECP2); however, the molecular mechanism by which these mutations mediate the RTT neuropathology remains enigmatic. Specifically, although MeCP2 is known to act as a transcriptional repressor, analyses of the RTT brain at steady-state conditions detected numerous differentially expressed genes, while the changes in transcript levels were mostly subtle. Here we reveal an aberrant global pattern of gene expression, characterized predominantly by higher levels of expression of activity-dependent genes, and anomalous alternative splicing events, specifically in response to neuronal activity in a mouse model for RTT. Notably, the specific splicing modalities of intron retention and exon skipping displayed a significant bias toward increased retained introns and skipped exons, respectively, in the RTT brain compared with the WT brain. Furthermore, these aberrations occur in conjunction with higher seizure susceptibility in response to neuronal activity in RTT mice. Our findings advance the concept that normal MeCP2 functioning is required for fine-tuning the robust and immediate changes in gene transcription and for proper regulation of alternative splicing induced in response to neuronal stimulation.

Extracellular Release of ILEI/FAM3C and Amyloid-β Is Associated with the Activation of Distinct Synapse Subpopulations

2021 ◽  
pp. 1-16
Author(s):  
Masaki Nakano ◽  
Yachiyo Mitsuishi ◽  
Lei Liu ◽  
Naoki Watanabe ◽  
Emi Hibino ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Epithelial Mesenchymal Transition ◽  
Surrogate Marker ◽  
Amyloid Β ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Extracellular Release ◽  
Activity Dependent ◽  
Aβ Production

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.

scholarly journals AMPA receptor inhibition by synaptically released zinc

2015 ◽  
Vol 112 (51) ◽  
pp. 15749-15754 ◽  
Author(s):  
Bopanna I. Kalappa ◽  
Charles T. Anderson ◽  
Jacob M. Goldberg ◽  
Stephen J. Lippard ◽  
Thanos Tzounopoulos
Keyword(s):  
Dorsal Cochlear Nucleus ◽  
Fine Tuning ◽  
Receptor Inhibition ◽  
Endogenous Modulator ◽  
Excitatory Neurotransmission ◽  
Zinc Levels ◽  
Zinc Inhibition ◽  
Endogenous Modulators ◽  
Activity Dependent

The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.

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

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.

scholarly journals Coupling of L-Type Ca2+ Channels to KV7/KCNQ Channels Creates a Novel, Activity-Dependent, Homeostatic Intrinsic Plasticity

2008 ◽  
Vol 100 (4) ◽  
pp. 1897-1908 ◽  
Author(s):  
Wendy W. Wu ◽  
C. Savio Chan ◽  
D. James Surmeier ◽  
John F. Disterhoft
Keyword(s):  
Pyramidal Neurons ◽  
Firing Frequency ◽  
Fine Tuning ◽  
Membrane Excitability ◽  
Kcnq Channels ◽  
Central Neurons ◽  
Subsequent Activation ◽  
Intrinsic Plasticity ◽  
Dependent Modification ◽  
Activity Dependent

Experience-dependent modification in the electrical properties of central neurons is a form of intrinsic plasticity that occurs during development and has been observed following behavioral learning. We report a novel form of intrinsic plasticity in hippocampal CA1 pyramidal neurons mediated by the KV7/KCNQ and CaV1/L-type Ca2+ channels. Enhancing Ca2+ influx with a conditioning spike train (30 Hz, 3 s) potentiated the KV7/KCNQ channel function and led to a long-lasting, activity-dependent increase in spike frequency adaptation—a gradual reduction in the firing frequency in response to sustained excitation. These effects were abolished by specific blockers for CaV1/L-type Ca2+ channels, KV7/KCNQ channels, and protein kinase A (PKA). Considering the widespread expression of these two channel types, the influence of Ca2+ influx and subsequent activation of PKA on KV7/KCNQ channels may represent a generalized principle in fine tuning the output of central neurons that promotes stability in firing—an example of homeostatic regulation of intrinsic membrane excitability.

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

eLife ◽  
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.

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

2017 ◽  
Vol 8 (1) ◽  
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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