scholarly journals Neuronal Activity Drives Astroglial Connexin 30 in Perisynaptic Processes and Shapes Its Functions

2019 ◽  
Vol 30 (2) ◽  
pp. 753-766 ◽  
Author(s):  
Grégory Ghézali ◽  
Flora Vasile ◽  
Nathan Curry ◽  
Marcus Fantham ◽  
Giselle Cheung ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Cognitive Processes ◽  
Transgenic Animals ◽  
Lysosomal Degradation ◽  
Dynamic Interactions ◽  
Superresolution Imaging ◽  
Protein Levels ◽  
Brain Functions ◽  
Connexin 30 ◽  
Activity Dependent

Abstract Astrocytes play key roles in brain functions through dynamic interactions with neurons. One of their typical features is to express high levels of connexins (Cxs), Cx43 and Cx30, the gap junction (GJ)-forming proteins. Cx30 is involved in basic cognitive processes and shapes synaptic and network activities, as shown by recent studies in transgenic animals. Yet it remains unknown whether astroglial Cx30 expression, localization, and functions are endogenously and dynamically regulated by neuronal activity and could therefore play physiological roles in neurotransmission. We here show that neuronal activity increased hippocampal Cx30 protein levels via a posttranslational mechanism regulating lysosomal degradation. Neuronal activity also increased Cx30 protein levels at membranes and perisynaptic processes, as revealed by superresolution imaging. This translated at the functional level in the activation of Cx30 hemichannels and in Cx30-mediated remodeling of astrocyte morphology independently of GJ biochemical coupling. Altogether, these data show activity-dependent dynamics of Cx30 expression, perisynaptic localization, and functions.

scholarly journals Cdk5-dependent phosphorylation of liprinα1 mediates neuronal activity-dependent synapse development

2017 ◽  
Vol 114 (33) ◽  
pp. E6992-E7001 ◽  
Author(s):  
Huiqian Huang ◽  
Xiaochen Lin ◽  
Zhuoyi Liang ◽  
Teng Zhao ◽  
Shengwang Du ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Excitatory Synapses ◽  
Synapse Development ◽  
Synaptic Localization ◽  
Superresolution Imaging ◽  
Functional Maturation ◽  
Dendritic Spine Morphology ◽  
Brain Circuitry ◽  
Activity Dependent

The experience-dependent modulation of brain circuitry depends on dynamic changes in synaptic connections that are guided by neuronal activity. In particular, postsynaptic maturation requires changes in dendritic spine morphology, the targeting of postsynaptic proteins, and the insertion of synaptic neurotransmitter receptors. Thus, it is critical to understand how neuronal activity controls postsynaptic maturation. Here we report that the scaffold protein liprinα1 and its phosphorylation by cyclin-dependent kinase 5 (Cdk5) are critical for the maturation of excitatory synapses through regulation of the synaptic localization of the major postsynaptic organizer postsynaptic density (PSD)-95. Whereas Cdk5 phosphorylates liprinα1 at Thr701, this phosphorylation decreases in neurons in response to neuronal activity. Blockade of liprinα1 phosphorylation enhances the structural and functional maturation of excitatory synapses. Nanoscale superresolution imaging reveals that inhibition of liprinα1 phosphorylation increases the colocalization of liprinα1 with PSD-95. Furthermore, disruption of liprinα1 phosphorylation by a small interfering peptide, siLIP, promotes the synaptic localization of PSD-95 and enhances synaptic strength in vivo. Our findings collectively demonstrate that the Cdk5-dependent phosphorylation of liprinα1 is important for the postsynaptic organization during activity-dependent synapse development.

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.

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 ApoE4 attenuates cortical neuronal activity and impairs memory in young apoE4 rats

2021 ◽  
Author(s):  
Ilona Har-Paz ◽  
Elor Arieli ◽  
Anan Moran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Neuronal Activity ◽  
Genetic Risk ◽  
Cortical Neurons ◽  
Late Onset ◽  
Genetic Risk Factor ◽  
Normal Brain ◽  
Brain Functions

AbstractThe E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD related neuropathology. Understanding these primary dysfunctions is vital for early detection of AD and the development of therapeutic strategies for it. Recently we have shown impaired extra-hippocampal memory in young apoE4 mice – a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we test the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 and wildtype rats, before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young apoE4 rats showed impaired CTA learning, consistent with our previous results in apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Single neuron and ensemble analyses of taste coding demonstrated that apoE4 neurons could be used to correctly classify tastes, but were unable to undergo plasticity to support learning. Our results suggest that apoE4 impacts brain excitability and plasticity early in life and may act as an initiator for later AD pathologies.Significant statementThe ApoE4 allele is the strongest genetic risk-factor for late-onset Alzheimer’s disease (AD), yet the link between apoE4 and AD is still unclear. Recent molecular and in-vitro studies suggest that apoE4 interferes with normal brain functions decades before the development of its related AD neuropathology. Here we recorded the activity of cortical neurons from young apoE4 rats during extra-hippocampal learning to study early apoE4 neuronal activity abnormalities, and their effects over coding capacities. We show that apoE4 drastically reduces basal and stimuli-evoked cortical activity in both excitatory and inhibitory neurons. The apoE4-induced activity attenuation did not prevent coding of stimuli identity and valence, but impaired capacity to undergo activity changes to support learning. Our findings support the hypothesis that apoE4 interfere with normal neuronal plasticity early in life; a deficit that may lead to late-onset AD development.

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.

scholarly journals Neuronal Activity-Dependent Control of Postnatal Neurogenesis and Gliogenesis

2018 ◽  
Vol 41 (1) ◽  
pp. 139-161 ◽  
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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