Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome

Fragile X syndrome (FXS) is the leading monogenetic cause of cognitive impairment and autism spectrum disorder. Area CA1 of the hippocampus receives current information about the external world from the entorhinal cortex via the temporoammonic (TA) pathway. Given its role in learning and memory, it is surprising that little is known about TA long-term potentiation (TA-LTP) in FXS. We found that TA-LTP was impaired in fmr1 KO mice. Furthermore, dendritic Ca2+ influx was smaller and dendritic spike threshold was depolarized in fmr1 KO mice. Dendritic spike threshold and TA-LTP were restored by block of A-type K+ channels. The impairment of TA-LTP coupled with enhanced Schaffer collateral LTP may contribute to spatial memory alterations in FXS. Furthermore, as both of these LTP phenotypes are attributed to changes in A-type K+ channels in FXS, our findings provide a potential therapeutic target to treat cognitive impairments in FXS.

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Faculty Opinions recommendation of Stress-induced alternative splicing of acetylcholinesterase results in enhanced fear memory and long-term potentiation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020586.232683 ◽

2004 ◽

Author(s):

L. Alison McInnes

Keyword(s):

Alternative Splicing ◽

Long Term Potentiation ◽

Fear Memory ◽

Term Potentiation

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Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

Scientific Reports ◽

10.1038/s41598-021-94992-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Christina F. de Veij Mestdagh ◽

Jaap A. Timmerman ◽

Frank Koopmans ◽

Iryna Paliukhovich ◽

Suzanne S. M. Miedema ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Memory Performance ◽

Long Term Potentiation ◽

Fear Memory ◽

Contextual Fear ◽

Contextual Fear Memory ◽

Model Of Alzheimer’S Disease ◽

Term Potentiation

AbstractHibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.

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The entorhinal cortex modulates trace fear memory formation and neuroplasticity in the mouse lateral amygdala via cholecystokinin

eLife ◽

10.7554/elife.69333 ◽

2021 ◽

Vol 10 ◽

Author(s):

Hemin Feng ◽

Junfeng Su ◽

Wei Fang ◽

Xi Chen ◽

Jufang He

Keyword(s):

Entorhinal Cortex ◽

Neural Plasticity ◽

Long Term Potentiation ◽

Fear Memory ◽

Memory Formation ◽

Loss Of Function ◽

Trace Fear Conditioning ◽

Term Potentiation ◽

Auditory Response ◽

Trace Fear

Although fear memory formation is essential for survival and fear-related mental disorders, the neural circuitry and mechanism are incompletely understood. Here, we utilized trace fear conditioning to study the formation of trace fear memory in mice. We identified the entorhinal cortex (EC) as a critical component of sensory signaling to the amygdala. We adopted both loss-of-function and gain-of-function experiments to demonstrate that release of the cholecystokinin (CCK) from the EC is required for trace fear memory formation. We discovered that CCK-positive neurons project from the EC to the lateral nuclei of the amygdala (LA), and inhibition of CCK-dependent signaling in the EC prevented long-term potentiation of the auditory response in the LA and formation of trace fear memory. In summary, high-frequency activation of EC neurons triggers the release of CCK in their projection terminals in the LA, potentiating auditory response in LA neurons. The neural plasticity in the LA leads to trace fear memory formation.

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