Amnesia after repeated head impact is caused by impaired synaptic plasticity in the memory engram

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. e1560232024 - e1560232024

Published: Jan. 16, 2024

Sub-concussive head impacts are associated with the development of acute and chronic cognitive deficits. We recently reported that high-frequency impact (HFHI) causes deficits in mice through synaptic changes. To better understand mechanisms underlying HFHI-induced memory decline, we used TRAP2/Ai32 transgenic to enable visualization manipulation engrams. labeled fear engram male female exposed an aversive experience subjected them sham or HFHI. Upon subsequent exposure natural recall cues, sham, but not HFHI mice, successfully retrieved fearful memories. In hippocampal neurons exhibited plasticity, evident amplified AMPA:NMDA ratio, enhanced AMPA-weighted tau, increased dendritic spine volume compared non-engram neurons. contrast, although retained a comparable number neurons, these did undergo plasticity. This lack plasticity coincided impaired activation network, leading retrograde amnesia mice. validated induced by stem from impairments artificially activating using optogenetics, found stimulated was identical both Our work shows impairment after is result deficiencies instead loss neuronal infrastructure, can reinstate forgotten amnestic brain stimulating engram. Targeting may have therapeutic potential for treating caused repeated impacts.

Language: Английский

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Advances in fear memory erasure and its neural mechanisms

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

In nature, animals must learn to recognize danger signals and respond immediately threats improve their environmental adaptation. However, excessive fear responses can lead diseases such as post-traumatic stress disorder, wherein traumatic events result in persistent memories. Therefore, erasing pathological memories vivo is a crucial topic neuroscience for understanding the nature of treating clinically relevant diseases. This article reviews recent studies on memory erasure, erasure short- long-term memory, neuroplasticity, neural circuitry molecular mechanisms roles engram cells perineuronal nets erasure. Research mechanism limited, plausible explanation essential difference between extinction still needs be provided. Notably, this review may guide future its underlying mechanisms, which help develop novel treatment strategies anxiety, other mental disorders.

Language: Английский

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Synaptic Plasticity in the Hippocampus

Oxford University Press eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 405 - 500

Published: Jan. 1, 2025

Abstract This chapter provides an overview of activity-dependent synaptic plasticity in the hippocampus. It outlines basic properties long-term potentiation (LTP) and depression (LTD) pathways that form core hippocampal trisynaptic circuit, notably Schaffer collateral/commissural (SCC) pathway connecting CA3 to CA1 pyramidal cells. Other significant include projections from medial later entorhinal cortex (EC) distal dendrites principal cells all subfields mossy fiber projection dendate granule The then delves into physiological cell biological mechanisms its contribution hippocampus-dependent memory, including relationship engrams. Another major focus is role dysregulated synaptopathies, with a particular emphasis on neurodevelopmental, psychiatric neurodegenerative brain disorders.

Language: Английский

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Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 4, 2025

Pain and itch are aversive sensations with distinct qualities, processed in overlapping pathways brain regions, including the anterior cingulate cortex (ACC), which is critical for their affective dimensions. However, cellular mechanisms underlying processing ACC remain unclear. Here, we identify modality-specific neuronal populations layer II/III of mice involved pain processing. Using a synapse labeling tool, show that pain- itch-related neurons selectively receive synaptic inputs from mediodorsal thalamic activated by stimuli, respectively. Chemogenetic inhibition these reduced pruriception or nociception without affecting opposite modality. Conversely, activation did not enhance stimulus-specific responses but commonly increased freezing-like behavior. These findings reveal information involves activity-dependent populations, functionally subsets.

Language: Английский

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Sleep Deprivation Alters Hippocampal Dendritic Spines in a Contextual Fear Memory Engram

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Abstract Sleep is critically involved in strengthening memories. However, our understanding of the morphological changes underlying this process still emerging. Recent studies suggest that specific subsets dendritic spines are strengthened during sleep neurons recent learning. Contextual memories associated with traumatic experiences post-traumatic stress disorder (PTSD) and represent learning may be sleep. We tested hypothesis encoding contextual fear selectively Furthermore, we how deprivation after initial impacts following re-exposure to conditioning. used ArcCreER T2 mice visualize encode (Arc+ neurons), concomitantly labeled did not (Arc-neurons). Dendritic branches Arc+ Arc-neurons were sampled using confocal imaging assess spine densities three-dimensional image analysis from either deprived (SD) or control allowed normally. Mushroom displayed decreased density SD mice, indicating upscaling mushroom In comparison, no observed Arc-branches. When animals re-exposed conditioning 4 weeks later, lower both Arc-branches, as well thin Arc-branches trial. Our findings indicate strengthens recently encoded memory, impairs initially later re-exposure. a experience thus viable strategy weakening strength trauma PTSD.

Language: Английский

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