Biology subjects

Abdou, K.

Publications and source records attributed to Abdou, K..

6 recordsLinked to original sources

bioRxiv2026

Silent hippocampal engrams shape future memory processing

The hippocampus harbors silent memory traces even when memory recall is absent. It is unknown why these traces persist and whether they remain sensitive to future episodes. We trained mice on the hippocampal-dependent novel object place recognition task and tracked the transition of the engram from a latent to a silent phase, which still held a functional memory trace. When mice were exposed to a weaker, modified version of their original memories, silent engrams led to better consolidation of these new events than their latent predecessors. Bidirectional manipulation of the engrams state, as well as artificially prolonging its latent state, successfully reversed its effect on the second memory. The silent engram state consistently displayed higher neuronal reactivation during the second event compared to the latent one, which may explain its preferential effect on its consolidation. Our results reveal previously unknown cognitive and activation dynamics for this behaviorally silent state.

animal behavior and cognition↗

bioRxiv2021

Uncovering long-term existence of a silent short-term memory trace

Active recall of short-term memory (STM) is known to last for a few hours, but whether STM has long-term functions is unknown. Here we show that, STM can be optogenetically retrieved at a time point during which natural recall is not possible, uncovering the long-term existence of a silent STM engram. Moreover, re-training within 3 days led to natural long-term recall, indicating facilitated consolidation. Calcium imaging revealed hippocampal CA1 reactivations of the STM trace during post-learning sleep. Inhibiting offline CA1 activity, N-methyl-D-aspartate receptor activity, or protein synthesis after first exposure to the STM-forming event impaired the future re-exposure-facilitated consolidation, which highlights a role of protein synthesis and sleep in storing a silent STM trace. These results provide evidence that STM is not completely lost within hours and demonstrates a possible two-step STM consolidation, first storage as a silent engram, then transformation into an active state by recurrence within 3 days.

neuroscience↗

bioRxiv2021

Inspiring cognitive inference in a cortical network during REM sleep

Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving1-4. However, it remains unclear how and when the subconscious brain can create novel ideas. Here, we show coordinated roles of non-rapid eye movement (NREM) and rapid-eye movement (REM) sleep in weaving inferential information from learned information. In a transitive inference paradigm, mice gained the inference one day, but not shortly, after complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either NREM or REM sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca2+ imaging showed gradual development of inference-related representation, peaking at post-training REM sleep. Neurons representing learned information co-reactivated significantly during post-training NREM sleep, while their co-reactivation with neurons representing inferential information was significantly higher during REM sleep. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialogue during only REM sleep created inferential knowledge. These findings suggest that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.

neuroscience↗

bioRxiv2021

Offline knowledge assimilations ensue online obscurity to inspire implicit learning

Passive priming of prior knowledge to assimilate ongoing experiences underlies advanced cognitive processing. However, the necessary neural dynamics of memory assimilation remains elusive. Uninstructed brain could also show boosted creativity, particularly after idling states, yet it remains unclear whether the idling brain can spontaneously spark relevant knowledge assimilations. We established a paradigm that links/separates context-dependent memories according to geometrical similarities. Mice exploring one of four contexts one day before undergoing contextual fear conditioning in a square context showed a gradual fear transfer to pre-exposed geometrically relevant contexts next day, but not after 15 min. Anterior cingulate cortex neurons representing relevant, rather than distinct, memories were significantly co-reactivated during post-conditioning sleep only, before their selective integration next day during testing. Disrupting sleep co-reactivations prevented assimilation while preserving recent memory consolidation. Thus, assimilating pertinent memories during sleep through co-reactivation of their respective engrams represents the neural underpinnings of sleep-triggered implicit cortical learning.

neuroscience↗

bioRxiv2017

Autophagy enhances memory erasure through synaptic destabilization

There is substantial interest in memory reconsolidation as a target for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). However, its applicability is restricted by reconsolidation-resistant conditions that constrain the initial memory destabilization. In this study, we investigated whether the induction of synaptic protein degradation through autophagy modulation, a major protein degradation pathway, can enhance memory destabilization upon retrieval and whether it can be utilized to overcome these conditions. Here, using male mice in an auditory fear reconsolidation model, we showed that autophagy contributes to memory destabilization and its induction can be utilized to enhance erasure of a reconsolidation-resistant auditory fear memory that depended on -amino-3-hydroxy-5-methyl4-isoxazolepropionic acid receptor (AMPAR) endocytosis. Using male mice in a contextual fear reconsolidation model, autophagy induction in the amygdala or in the hippocampus enhanced fear or contextual memory destabilization, respectively. The latter correlated with AMPAR degradation in the spines of the contextual memory-ensemble cells. Using male rats in an in vivo long-term potentiation reconsolidation model, autophagy induction enhanced synaptic destabilization in an N-methyl-D-aspartate receptor-dependent manner. These data indicate that induction of synaptic protein degradation can enhance both synaptic and memory destabilization upon reactivation and that autophagy inducers have the potential to be used as a therapeutic tool in the treatment of anxiety disorders.\n\nSignificance StatementIt has been reported that inhibiting synaptic protein degradation prevents memory destabilization. However, whether the reverse relation is true and whether it can be utilized to enhance memory destabilization is still unknown. Here we addressed this question on the behavioral, molecular and synaptic levels, and showed that induction of autophagy, a major protein degradation pathway, can enhance memory and synaptic destabilization upon reactivation. We also show that autophagy induction can be utilized to overcome a reconsolidation-resistant memory, suggesting autophagy inducers as a potential therapeutic tool in the treatment of anxiety disorders.

neuroscience↗

bioRxiv2017

Glucocorticoid receptor-mediated amygdalar metaplasticity underlies adaptive modulation of fear memory by stress

Glucocorticoid receptor (GR) is crucial for signaling mediated by stress-induced high levels of glucocorticoids. The lateral nucleus of the amygdala (LA) is a key structure underlying auditory-cued fear conditioning. Here, we demonstrate that genetic disruption of GR in the LA (LAGRKO) resulted in an auditory-cued fear memory deficit for strengthened conditioning. Furthermore, the suppressive effect of a single restraint stress (RS) prior to conditioning on auditory-cued fear memory in floxed GR (control) mice was abolished in LAGRKO mice. Optogenetic induction of long-term depression (LTD) at auditory inputs to the LA reduced auditory-cued fear memory in RS-exposed LAGRKO mice, and in contrast, optogenetic induction of long-term potentiation (LTP) increased auditory-cued fear memory in RS-exposed floxed GR mice. These findings suggest that prior stress suppresses fear conditioning-induced LTP at auditory inputs to the LA in a GR-dependent manner, thereby protecting animals from encoding excessive cued fear memory under stress conditions.

neuroscience↗