Spatial transcriptomics reveal neuron–astrocyte synergy in long-term memory

Nature, Год журнала: 2024, Номер 627(8003), С. 374 - 381

Опубликована: Фев. 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

Язык: Английский

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Assessments of dentate gyrus function: discoveries and debates

Nature reviews. Neuroscience, Год журнала: 2023, Номер 24(8), С. 502 - 517

Опубликована: Июнь 14, 2023

Язык: Английский

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Engram neurons: Encoding, consolidation, retrieval, and forgetting of memory

Molecular Psychiatry, Год журнала: 2023, Номер 28(8), С. 3207 - 3219

Опубликована: Июнь 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.

Язык: Английский

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Understanding the physical basis of memory: Molecular mechanisms of the engram

Journal of Biological Chemistry, Год журнала: 2022, Номер 298(5), С. 101866 - 101866

Опубликована: Март 26, 2022

Memory, defined as the storage and use of learned information in brain, is necessary to modulate behavior critical for animals adapt their environments survive. Despite being a cornerstone brain function, questions surrounding molecular cellular mechanisms how encoded, stored, recalled remain largely unanswered. One widely held theory that an engram formed by group neurons are active during learning, which undergoes biochemical physical changes store stable state, later reactivated recall memory. In past decade, development labeling methodologies has proven useful investigate biology memory at levels. Engram technology allows study individual memories associated with particular experiences evolution over time, enough experimental resolution discriminate between different processes: learning (encoding), consolidation (the passage from short-term long-term memories), maintenance brain). Here, we review current understanding formation level focusing on insights provided using technology.

Язык: Английский

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Incorporating neuro-inspired adaptability for continual learning in artificial intelligence

Nature Machine Intelligence, Год журнала: 2023, Номер 5(12), С. 1356 - 1368

Опубликована: Ноя. 16, 2023

Язык: Английский

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Memory circuits in dementia: The engram, hippocampal neurogenesis and Alzheimer’s disease

Progress in Neurobiology, Год журнала: 2024, Номер 236, С. 102601 - 102601

Опубликована: Апрель 1, 2024

Here, we provide an in-depth consideration of our current understanding engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health Alzheimer's disease (AD). This review highlights novel findings these emerging research fields future directions for therapeutic avenues memory failure dementia. Engrams, AD, neurogenesis have each been extensively studied. The integration topics, however, has relatively less deliberated, is the focus this review. We primarily on dentate gyrus (DG) hippocampus, which a key area episodic formation. Episodic significantly impaired also site adult neurogenesis. Advancements technology, especially opto- chemogenetics, made sophisticated manipulations engram cells possible. Furthermore, innovative methods emerged monitoring neurons, even specific neuronal populations, vivo while animals engage tasks, such as calcium imaging. In imaging contributes more comprehensive cells. Critically, studies DG using technologies shown important contribution both AD. Together, discussion topics provides holistic perspective that motivates questions research.

Язык: Английский

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Adaptive expression of engrams by retroactive interference

Cell Reports, Год журнала: 2023, Номер 42(8), С. 112999 - 112999

Опубликована: Авг. 1, 2023

Long-term memories are stored as configurations of neuronal ensembles, termed engrams. Although investigation engram cell properties and functionality in memory recall has been extensive, less is known about how cells affected by forgetting. We describe a form interference-based forgetting using an object behavioral paradigm. By activity-dependent labeling, we show that although retroactive interference results decreased reactivation during trials, optogenetic stimulation the labeled sufficient to induce retrieval. Forgotten engrams may be reinstated via presentation similar or related environmental information. Furthermore, demonstrate activity necessary for occur. Taken together, these findings indicate modules expression manner both reversible updatable. Inference constitute adaptive where, everyday life, new perceptual inputs modulate natural process.

Язык: Английский

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Engram cell connectivity as a mechanism for information encoding and memory function

Current Biology, Год журнала: 2023, Номер 33(24), С. 5368 - 5380.e5

Опубликована: Ноя. 21, 2023

Язык: Английский

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Silencing dentate newborn neurons alters excitatory/inhibitory balance and impairs behavioral inhibition and flexibility

Science Advances, Год журнала: 2024, Номер 10(2)

Опубликована: Янв. 10, 2024

Adult neurogenesis confers the hippocampus with unparalleled neural plasticity, essential for intricate cognitive functions. The specific influence of sparse newborn neurons (NBNs) in modulating activities and subsequently steering behavior, however, remains obscure. Using an engineered NBN-tetanus toxin mouse model (NBN-TeTX), we noninvasively silenced NBNs, elucidating their crucial role impulse inhibition flexibility as evidenced through Morris water maze reversal learning Go/Nogo task operant learning. Task-based functional MRI (tb-fMRI) paired revealed dorsal hippocampal hyperactivation during Nogo male NBN-TeTX mice, suggesting that hyperexcitability might underlie observed behavioral deficits. Additionally, resting-state fMRI (rs-fMRI) exhibited enhanced connectivity between ventral dentate gyrus following NBN silencing. Further investigations into PV

Язык: Английский

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Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice

Molecular Psychiatry, Год журнала: 2024, Номер 29(11), С. 3316 - 3329

Опубликована: Май 8, 2024

Язык: Английский

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