Astrocytic Foxo1 regulates hippocampal spinogenesis and synaptic plasticity to enhance fear memory DOI Open Access
João Filipe Viana, Sónia Guerra‐Gomes, Daniela Sofia Abreu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 1, 2023

ABSTRACT Astrocytes are active players in brain circuits, sensing and responding to neuronal activity, impacting behavior production. Activation of astrocytes triggers intracellular calcium elevations displaying complex spatiotemporal properties. Intracellular activity is thought underlie synaptic transmission, metabolism, homeostasis modulation. However, the calcium-dependent signaling pathways involved these processes poorly understood, representing a critical knowledge gap this field. To reveal circuit structure function, we performed multi-level analysis inositol 1,4,5-triphosphate receptor type 2 knockout (IP3R2 KO) mouse model which lacks somatic specifically astrocytes. We focused on hippocampus, region responsible for cognitive function emotional behaviors. The transcriptomic hippocampal tissue revealed that lack astrocytic causes differential expression hundreds genes. Among these, 76 genes regulated by astrocyte-specific Foxo1 transcription factor. This factor over-expressed regulates spinogenesis coverage. A detailed morphological pyramidal neurons dendrites with shift more immature spine profile. profile may previously described reduction long-term depression performance fear memory tasks observed model. Indeed, confirmed mice lacking display an enhancement memory. verify causal relationship between structural, synaptic, behavioral observations, used viral approach induce over-expression naïve C57BL/6J mice. viral-driven stratum radiatum replicated crossing territory led same region. Finally, manipulation was sufficient enhance characterization modulate through

Language: Английский

The Synucleins and the Astrocyte DOI Creative Commons
Abigail J. Myers,

Ayat Brahimi,

Imani J. Jenkins

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(2), P. 155 - 155

Published: Jan. 19, 2023

Synucleins consist of three proteins exclusively expressed in vertebrates. α-Synuclein (αS) has been identified as the main proteinaceous aggregate Lewy bodies, a pathological hallmark many neurodegenerative diseases. Less is understood about β-synuclein (βS) and γ-synuclein (γS), although it known βS can interact with αS vivo to inhibit aggregation. Likewise, both γS αS’s propensity vitro. In central nervous system, αS, lesser extent γS, are highly neural presynaptic terminal, they not strictly located there, emerging data have shown more complex expression profile. Synapse loss astrocyte atrophy early aspects degenerative diseases brain correlate disease progression. appear be involved synaptic transmission, astrocytes coordinate organize function, excess degraded by microglia adjacent synapse. also observed may provide beneficial roles. The astrocytic responsibility for degradation well evidence on possible functions warrant closer inspection astrocyte–synuclein interactions at

Language: Английский

Citations

8

Reactive astrocytes mediate postoperative surgery-induced anxiety through modulation of GABAergic signalling in the zona incerta of mice DOI Creative Commons
Kun Tong, Yutong Song,

Si-Qi Jing

et al.

British Journal of Anaesthesia, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Surgery can induce severe neuroinflammation and negative emotional symptoms, such as anxiety-like behaviour. We studied whether reactive astrocytes in the zona incerta (ZI) mediate surgery-induced anxiety mice.

Language: Английский

Citations

2

Reinforcing Interdisciplinary Collaborations to Unravel the Astrocyte “Calcium Code” DOI Creative Commons
Ana Covelo, Anaïs Badoual, Audrey Denizot

et al.

Journal of Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 72(7), P. 1443 - 1455

Published: May 11, 2022

Abstract In this review article, we present the major insights from and challenges faced in acquisition, analysis modeling of astrocyte calcium activity, aiming at bridging gap between those fields to crack complex “Calcium Code”. We then propose strategies reinforce interdisciplinary collaborative projects unravel function health disease.

Language: Английский

Citations

10

Probing microdomain Ca2+ activity and synaptic transmission with a node-based tripartite synapse model DOI Creative Commons
Langzhou Liu, Huayi Gao,

Jinyu Li

et al.

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

Published: Feb. 10, 2023

Astrocytic fine processes are the most minor structures of astrocytes but host much Ca 2+ activity. These localized signals spatially restricted to microdomains crucial for information processing and synaptic transmission. However, mechanistic link between astrocytic nanoscale microdomain activity remains hazily understood because technical difficulties in accessing this structurally unresolved region. In study, we used computational models disentangle intricate relations morphology local dynamics involved processes. We aimed answer: 1) how nano-morphology affects transmission, 2) affect large process they connect. To address these issues, undertook following two modeling: integrated vivo astrocyte morphological data from a recent study performed with super-resolution microscopy that discriminates sub-compartments various shapes, referred as nodes shafts classic IP 3 R-mediated signaling framework describing intracellular dynamics, proposed node-based tripartite synapse model linking predict effect structural deficits on Extensive simulations provided us several biological insights: width could strongly influence spatiotemporal variability properties what indeed determined was ratio shafts, connectivity larger markedly shaped signal parent rather than itself, 3) changes part might potentially induce abnormality transmission by affecting level glutamate at synapses. Taken together, comprehensive which theoretical computation highlights role nanomorphology its possible mechanisms related pathological conditions.

Language: Английский

Citations

6

Astrocyte regulation of extracellular space parameters across the sleep-wake cycle DOI Creative Commons
Sandhya Sriram,

Kaira Carstens,

Wayne Dewing

et al.

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

Published: June 26, 2024

Multiple subfields of neuroscience research are beginning to incorporate astrocytes into current frameworks understanding overall brain physiology, neuronal circuitry, and disease etiology that underlie sleep sleep-related disorders. Astrocytes have emerged as a dynamic regulator activity through control extracellular space (ECS) volume composition, both which can vary dramatically during different levels arousal. also an attractive target due their prominent role in the glymphatic system, method by toxic metabolites generated wakefulness cleared away. In this review we assess literature surrounding glial influences on fluctuations ECS composition across sleep-wake cycle. We examine mechanisms astrocyte regulation solute clearance wake states. Overall, findings highlight importance research.

Language: Английский

Citations

1

Computational Models of Astrocyte Function at Glutamatergic Synapses DOI
Kerstin Lenk, Audrey Denizot, Barbara Genocchi

et al.

Neuromethods, Journal Year: 2024, Volume and Issue: unknown, P. 229 - 263

Published: Jan. 1, 2024

At tripartite synapses, astrocytes are in close contact with neurons and contribute to various functions, from synaptic transmission, maintenance of ion homeostasis, glutamate uptake metabolism. However, disentangling the precise contribution those phenomena underlying biochemical mechanisms is remarkably challenging. This notably results their highly ramified morphology, nanoscopic size majority astrocyte processes, poorly understood information encoded by spatiotemporally diverse calcium signals. book chapter presents selected computational models involvement glutamatergic transmission. The goal this present representative function conjunction biological questions they can investigate.

Language: Английский

Citations

0

Active enhancement of synapse driven depolarization of perisynaptic astrocytic processes DOI Open Access
Ryo J. Nakatani, Erik De Schutter

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

Abstract Electrophysiological properties underlie the fundamental mechanisms of brain. Although astrocytes have typically been considered not electrically excitable, recent studies shown depolarization induced by local extracellular potassium changes caused neuronal activity. Interestingly, astro-cytic is only within periphery astrocyte, where contact neurons. This affects brain’s information processing, as alters astrocyte functionality and neurotransmit-ter dynamics. However, specific causing astrocytic remained unknown due to limitations experimental techniques. Here, we construct a computational whole-cell model containing experimen-tally verified channels relevant depolarization. Using our model, suggest that previously reported alone are insufficient for additional required. Our sim-ulations show NMDARs contribute this cooperating with Kir 4.1 actively enhance concentration and, thus, sustain

Language: Английский

Citations

0

Quantitative Optical Analysis of Astrocytic Ca2+ Signaling DOI
André Zeug, Petr Unichenko, Franziska E. Müller

et al.

Neuromethods, Journal Year: 2024, Volume and Issue: unknown, P. 21 - 57

Published: Jan. 1, 2024

Language: Английский

Citations

0

Beyond neurons: computer vision methods for analysis of morphologically complex astrocytes DOI Creative Commons
Tabish A. Syed, Mohammed Youssef, Alexandra L. Schober

et al.

Frontiers in Computer Science, Journal Year: 2024, Volume and Issue: 6

Published: Sept. 25, 2024

The study of the geometric organization biological tissues has a rich history in literature. However, geometry and architecture individual cells within traditionally relied upon manual or indirect measures shape. Such rudimentary are largely result challenges associated with acquiring high resolution images cellular components, as well lack computational approaches to analyze large volumes high-resolution data. This is especially true brain tissue, which composed complex array cells. Here we review tools that have been applied unravel nanoarchitecture astrocytes, type cell increasingly being shown be essential for function. Astrocytes among most structurally functionally diverse mammalian body partner neurons. Light microscopy does not allow adequate astrocyte morphology, however, large-scale serial electron data, provides nanometer 3D models, enabling visualization fine, convoluted structure astrocytes. Application computer vision methods resulting nanoscale models helping reveal organizing principles but complete understanding its functional implications will require further adaptation existing tools, development new approaches.

Language: Английский

Citations

0

Astrocytic Foxo1 regulates hippocampal spinogenesis and synaptic plasticity to enhance fear memory DOI Open Access
João Filipe Viana, Sónia Guerra‐Gomes, Daniela Sofia Abreu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 1, 2023

ABSTRACT Astrocytes are active players in brain circuits, sensing and responding to neuronal activity, impacting behavior production. Activation of astrocytes triggers intracellular calcium elevations displaying complex spatiotemporal properties. Intracellular activity is thought underlie synaptic transmission, metabolism, homeostasis modulation. However, the calcium-dependent signaling pathways involved these processes poorly understood, representing a critical knowledge gap this field. To reveal circuit structure function, we performed multi-level analysis inositol 1,4,5-triphosphate receptor type 2 knockout (IP3R2 KO) mouse model which lacks somatic specifically astrocytes. We focused on hippocampus, region responsible for cognitive function emotional behaviors. The transcriptomic hippocampal tissue revealed that lack astrocytic causes differential expression hundreds genes. Among these, 76 genes regulated by astrocyte-specific Foxo1 transcription factor. This factor over-expressed regulates spinogenesis coverage. A detailed morphological pyramidal neurons dendrites with shift more immature spine profile. profile may previously described reduction long-term depression performance fear memory tasks observed model. Indeed, confirmed mice lacking display an enhancement memory. verify causal relationship between structural, synaptic, behavioral observations, used viral approach induce over-expression naïve C57BL/6J mice. viral-driven stratum radiatum replicated crossing territory led same region. Finally, manipulation was sufficient enhance characterization modulate through

Language: Английский

Citations

0