mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory DOI Creative Commons
Vijendra Sharma, Maurício M. Oliveira,

Rapita Sood

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(49)

Published: Nov. 28, 2023

Activation of neuronal protein synthesis upon learning is critical for the formation long-term memory. Here, we report that in contextual fear conditioning paradigm engenders a decrease eIF2α (eukaryotic translation initiation factor 2) phosphorylation astrocytes hippocampal CA1 region, which promotes synthesis. Genetic reduction enhanced and spatial memory lowered threshold induction long-lasting plasticity by modulating synaptic transmission. Thus, learning-induced dephosphorylation bolsters consolidation memories.

Language: Английский

Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory DOI Creative Commons
Wenfei Sun, Zhihui Liu, Xian Jiang

et al.

Nature, Journal Year: 2024, Volume and Issue: 627(8003), P. 374 - 381

Published: Feb. 7, 2024

Abstract Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus has key role in long-term fear memory formation 1 . Here we used spatial single-cell transcriptomics to illuminate the cellular molecular architecture memory. We identified transcriptional signatures subpopulations neurons astrocytes were memory-specific persisted for weeks. These implicate neuropeptide BDNF signalling, MAPK CREB activation, ubiquitination pathways, synaptic connectivity as components Notably, upon formation, neuronal subpopulation defined by increased Penk decreased Tac expression constituted most prominent component engram amygdala. changes observed both with RNA sequencing single-molecule intact slices, providing rich map engram. data enabled us determine this interacts adjacent astrocytes, functional experiments show require interactions encode

Language: Английский

Citations

58
Neural dynamics underlying associative learning in the dorsal and ventral hippocampus DOI
Jeremy S. Biane, Max Ladow, Fabio Stefanini

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(5), P. 798 - 809

Published: April 3, 2023

Language: Английский

Citations

50
Engram neurons: Encoding, consolidation, retrieval, and forgetting of memory DOI Creative Commons

Axel Guskjolen,

Mark S. Cembrowski

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(8), P. 3207 - 3219

Published: June 27, 2023

Tremendous strides have been made in our understanding of the neurobiological substrates memory - so-called "engram". Here, we integrate recent progress engram field to illustrate how neurons transform across "lifespan" a from initial encoding, consolidation and retrieval, ultimately forgetting. To do so, first describe cell-intrinsic properties shape emergence at encoding. Second, highlight these encoding preferentially participate synaptic- systems-level memory. Third, changes during guide neural reactivation facilitate recall. Fourth, mechanisms forgetting, can counteract established consolidation, retrieval. Motivated by experimental results four sections, conclude proposing some conceptual extensions traditional view engram, including broadening cell-type participation within engrams stages. In collection, review synthesizes general principles stages, describes future avenues further understand dynamic engram.

Language: Английский

Citations

45
Centripetal integration of past events in hippocampal astrocytes regulated by locus coeruleus DOI Creative Commons
Peter Rupprecht, Sian N. Duss, Denise Becker

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(5), P. 927 - 939

Published: April 3, 2024

Abstract An essential feature of neurons is their ability to centrally integrate information from dendrites. The activity astrocytes, in contrast, has been described as mostly uncoordinated across cellular compartments without clear central integration. Here we report conditional integration calcium signals astrocytic distal processes at soma. In the hippocampus adult mice both sexes, found that global activity, recorded with population imaging, reflected past neuronal and behavioral events on a timescale seconds. Salient events, indicated by pupil dilations, facilitated propagation Centripetal soma was reproduced optogenetic activation locus coeruleus, key regulator arousal, reduced pharmacological inhibition α1-adrenergic receptors. Together, our results suggest astrocytes are computational units brain slowly conditionally upon behaviorally relevant events.

Language: Английский

Citations

25
Network-level encoding of local neurotransmitters in cortical astrocytes DOI Creative Commons
Michelle K. Cahill, Max Collard, Vincent Tse

et al.

Nature, Journal Year: 2024, Volume and Issue: 629(8010), P. 146 - 153

Published: April 17, 2024

Abstract Astrocytes, the most abundant non-neuronal cell type in mammalian brain, are crucial circuit components that respond to and modulate neuronal activity through calcium (Ca 2+ ) signalling 1–7 . Astrocyte Ca is highly heterogeneous occurs across multiple spatiotemporal scales—from fast, subcellular 3,4 slow, synchronized connected astrocyte networks 8–10 —to influence many processes 5,7,11 However, inputs drive network dynamics remain unclear. Here we used ex vivo two-photon imaging while mimicking neurotransmitter at scales. We find brief, of GABA glutamate lead widespread, long-lasting responses beyond an individual stimulated cell. Further, a key subset activity—propagative activity—differentiates these two main neurotransmitters, may future inputs. Together, our results demonstrate local, transient encoded by broad cortical over minutes-long time course, contributing accumulating evidence substantial astrocyte–neuron communication network-level scales 12–14 These findings will enable studies investigate link between specific functional outputs, which could build consistent framework for astrocytic modulation activity.

Language: Английский

Citations

23
The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis DOI
Miguel Marin-Rodero, Elisa Cintado, Alec J. Walker

et al.

Science Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on immunocytes guard homeostasis in healthy individuals remains limited. This study highlights heterogeneous, polyfunctional regulatory T cell (T reg ) compartment meninges. A subtype specialized controlling interferon-gamma (IFN-γ) responses another dedicated regulating follicular B were substantial components this compartment. Accordingly, punctual ablation rapidly unleashed IFN-γ production by lymphocytes, unlocked access parenchyma, altered profiles. Distally, hippocampus assumed a reactive state, with morphological transcriptional changes multiple glial types. Within dentate gyrus, neural stem underwent more death blocked from further differentiation, which coincided impairments short-term spatial-reference memory. Thus, regs multifaceted safeguard at steady state.

Language: Английский

Citations

3
Astrocyte ensembles manipulated with AstroLight tune cue-motivated behavior DOI
Irene Serra, C. Martín, Javier Sánchez Romero

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Language: Английский

Citations

3
Astrocyte heterogeneity and interactions with local neural circuits DOI Creative Commons
Matthew G. Holt

Essays in Biochemistry, Journal Year: 2023, Volume and Issue: 67(1), P. 93 - 106

Published: Feb. 7, 2023

Astrocytes are ubiquitous within the central nervous system (CNS). These cells possess many individual processes which extend out into neuropil, where they interact with a variety of other cell types, including neurons at synapses. now known to be active players in all aspects synaptic life cycle, synapse formation and elimination, maturation, maintenance homeostasis modulation transmission. Traditionally, astrocytes have been studied as homogeneous group cells. However, recent studies uncovered surprising degree heterogeneity their development function, suggesting that may matched support local circuits. Hence, better understanding astrocyte its implications needed understand brain function.

Language: Английский

Citations

40
Role of glia and extracellular matrix in controlling neuroplasticity in the central nervous system DOI Creative Commons
Egor Dzyubenko, Dirk M. Hermann

Seminars in Immunopathology, Journal Year: 2023, Volume and Issue: 45(3), P. 377 - 387

Published: April 13, 2023

Abstract Neuronal plasticity is critical for the maintenance and modulation of brain activity. Emerging evidence indicates that glial cells actively shape neuroplasticity, allowing highly flexible regulation synaptic transmission, neuronal excitability, network synchronization. Astrocytes regulate synaptogenesis, stabilize connectivity, preserve balance between excitation inhibition in networks. Microglia, brain-resident immune cells, continuously monitor sculpt synapses, remodeling circuits. Glia-mediated neuroplasticity driven by activity, controlled a plethora feedback signaling mechanisms crucially involves extracellular matrix central nervous system. This review summarizes key findings considering neurotransmission metabolic support astrocyte-neuronal networks, mediated microglia. Novel data indicate astrocytes microglia are pivotal controlling function, indicating necessity to rethink neurocentric views.

Language: Английский

Citations

34
Astrocytic modulation of neuronal signalling DOI Creative Commons

Sushmitha S. Purushotham,

Yossi Buskila

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

Published: June 1, 2023

Neuronal signalling is a key element in neuronal communication and essential for the proper functioning of CNS. Astrocytes, most prominent glia brain play role modulating at molecular, synaptic, cellular, network levels. Over past few decades, our knowledge about astrocytes their has evolved from considering them as merely glue that provides structural support to neurons, elements. Astrocytes can regulate activity neurons by controlling concentrations ions neurotransmitters extracellular milieu, well releasing chemicals gliotransmitters modulate activity. The aim this review summarise main processes through which are function. We will systematically distinguish between direct indirect pathways affect all Lastly, we summarize pathological conditions arise once these impaired focusing on neurodegeneration.

Language: Английский

Citations

29