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Nature Neuroscience Mar 2024Episodic memories are encoded by experience-activated neuronal ensembles that remain necessary and sufficient for recall. However, the temporal evolution of memory...
Episodic memories are encoded by experience-activated neuronal ensembles that remain necessary and sufficient for recall. However, the temporal evolution of memory engrams after initial encoding is unclear. In this study, we employed computational and experimental approaches to examine how the neural composition and selectivity of engrams change with memory consolidation. Our spiking neural network model yielded testable predictions: memories transition from unselective to selective as neurons drop out of and drop into engrams; inhibitory activity during recall is essential for memory selectivity; and inhibitory synaptic plasticity during memory consolidation is critical for engrams to become selective. Using activity-dependent labeling, longitudinal calcium imaging and a combination of optogenetic and chemogenetic manipulations in mouse dentate gyrus, we conducted contextual fear conditioning experiments that supported our model's predictions. Our results reveal that memory engrams are dynamic and that changes in engram composition mediated by inhibitory plasticity are crucial for the emergence of memory selectivity.
Topics: Mice; Animals; Memory Consolidation; Mental Recall; Neurons; Fear; Memory, Episodic
PubMed: 38243089
DOI: 10.1038/s41593-023-01551-w -
The European Journal of Neuroscience Aug 2019Drug addiction is an aberrant memory that shares the same memory processes as other memories. Brief exposure to drug-associated cues could result in reconsolidation, a... (Review)
Review
Drug addiction is an aberrant memory that shares the same memory processes as other memories. Brief exposure to drug-associated cues could result in reconsolidation, a hypothetical process during which original memory could be updated. In contrast, longer exposure times to drug-associated cues could trigger extinction, a process that decreases the conditioned responding. In this review, we discuss the pharmacological and non-pharmacological manipulations on the reconsolidation and extinction that could be used to interfere with drug reward memories. Pharmacological agents such as β-adrenergic receptor antagonist propranolol can interfere with reconsolidation to disrupt drug reward memory. Pharmacological agents such as the NMDA receptor glycine site agonists d-cycloserine and d-serine can facilitate extinction and then attenuate the expression of drug reward memory. Besides pharmacological interventions, drug-free behavioral approaches by utilizing the reconsolidation and extinction, such as 'post-retrieval extinction' and 'UCS-retrieval extinction', are also effective to erase or inhibit the recall of drug reward memory. Taken together, pharmacological modulation and non-pharmacological modulation of reconsolidation and extinction are promising approaches to regulate drug reward memory and prevent relapse.
Topics: Adrenergic beta-Antagonists; Animals; Conditioning, Classical; Extinction, Psychological; Humans; Memory; Mental Recall; Reward; Substance-Related Disorders
PubMed: 30113098
DOI: 10.1111/ejn.14072 -
Scientific Reports Jul 2022Humans have the remarkable ability to continually store new memories, while maintaining old memories for a lifetime. How the brain avoids catastrophic forgetting of...
Humans have the remarkable ability to continually store new memories, while maintaining old memories for a lifetime. How the brain avoids catastrophic forgetting of memories due to interference between encoded memories is an open problem in computational neuroscience. Here we present a model for continual learning in a recurrent neural network combining Hebbian learning, synaptic decay and a novel memory consolidation mechanism: memories undergo stochastic rehearsals with rates proportional to the memory's basin of attraction, causing self-amplified consolidation. This mechanism gives rise to memory lifetimes that extend much longer than the synaptic decay time, and retrieval probability of memories that gracefully decays with their age. The number of retrievable memories is proportional to a power of the number of neurons. Perturbations to the circuit model cause temporally-graded retrograde and anterograde deficits, mimicking observed memory impairments following neurological trauma.
Topics: Humans; Learning; Memory; Memory Consolidation; Neural Networks, Computer; Neurons
PubMed: 35907920
DOI: 10.1038/s41598-022-16407-9 -
Neuropsychologia Nov 2012Dual-process models of recognition memory distinguish between the retrieval of qualitative information about a prior event (recollection), and judgments of prior... (Review)
Review
Dual-process models of recognition memory distinguish between the retrieval of qualitative information about a prior event (recollection), and judgments of prior occurrence based on an acontextual sense of familiarity. fMRI studies investigating the neural correlates of memory encoding and retrieval conducted within the dual-process framework have frequently reported findings consistent with the view that the hippocampus selectively supports recollection, and has little or no role in familiarity-based recognition. An alternative interpretation of these findings has been proposed, however, in which it is argued that the hippocampus supports the encoding and retrieval of 'strong' memories, regardless of whether the memories are recollection- or familiarity-based. Here, we describe the findings of eight fMRI studies from our laboratory: one study of source memory encoding, four studies of the retrieval of contextual information, and three studies of continuous recognition. Together, the findings support the proposal that hippocampal activity co-varies with the amount of contextual information about a study episode that is encoded or retrieved, and not with the strength of an undifferentiated memory signal.
Topics: Hippocampus; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Memory; Mental Processes; Mental Recall
PubMed: 22732490
DOI: 10.1016/j.neuropsychologia.2012.06.004 -
Acta Neurochirurgica Oct 2023Since the late 1930s, electric brain stimulation (EBS) in awake patients has been known to occasionally elicit patient descriptions of a form of memory flashbacks, known... (Review)
Review
BACKGROUND
Since the late 1930s, electric brain stimulation (EBS) in awake patients has been known to occasionally elicit patient descriptions of a form of memory flashbacks, known as experiential phenomena. One understanding of these sensations are as caused by an augmentation of the capacity for memory retrieval. However, an alternative hypothesis holds that memory flashbacks during EBS are "synthetic constructions" in the form of mental events, falsely interpreted as memories.
METHODS
A critical narrative review is used to discuss the false memory hypothesis in relation to the current empirical literature and source attribution theory.
RESULTS
EBS as well as situational demands in the form of interaction between patient and neurosurgeon may both lead to the creation of mental events and influence their interpretation in a way that may create false memories. The false memory hypothesis provides a potential explanation for several apparent inconsistencies in the current literature such as (a) the fragmented nature of experiential reports, (b) the ability of EBS to induce memory retrieval errors in controlled studies, (c) that Penfield's elicitations of experiential phenomena are so rarely replicated in the modern era, and (d) the limited utility of techniques that elicit experiential phenomena in the treatment of memory disorders.
CONCLUSIONS
The hypothesis that experiential phenomena may largely be "synthetic constructions" deserves serious consideration by neurosurgeons.
Topics: Humans; Memory; Brain; Stereotaxic Techniques; Wakefulness; Electric Stimulation
PubMed: 35804269
DOI: 10.1007/s00701-022-05307-6 -
Brain Research Bulletin Mar 2023Karim Nader is rightly celebrated for his seminal studies on memory reconsolidation. This commentary celebrates another related contribution - his work on memory... (Review)
Review
Karim Nader is rightly celebrated for his seminal studies on memory reconsolidation. This commentary celebrates another related contribution - his work on memory maintenance by the autonomously active PKC isoform, PKMζ. There are two methods for "erasing" previously established long-term memory maintenance: 1) inhibiting PKMζ, and 2) blocking reconsolidation. Prior to Nader's research on PKMζ, these two forms of memory erasure were thought to be fundamentally different. Inhibiting PKMζ in a brain region disrupts memory held in storage. But if the inhibitor is injected into the same region immediately after memory retrieval, the drug has no effect. Conversely, inhibiting protein synthesis immediately after memory retrieval blocks reconsolidation. But protein synthesis inhibitors have no effect on memory held in storage without retrieval. The work of Paolo Virginia Migues, Nader, and colleagues, however, revealed an unexpected link between the mechanisms of memory maintenance by PKMζ and the kinase's regulation of postsynaptic AMPAR trafficking that potentiates synaptic transmission and expresses memory during retrieval. This insight led Matteo Bernabo, Nader, and colleagues to observe that memory retrieval first rapidly degrades PKMζ, and then induces the resynthesis of the kinase to restore maintenance of the retrieved memory. This finding explains why a PKMζ inhibitor such as ZIP, if injected in a brain region storing a memory, does not erase the memory immediately after retrieval - the kinase maintaining the retrieved memory has been degraded but not yet resynthesized. Moreover, Bernabo et al. showed that suppressing the resynthesis of PKMζ after its degradation prevents memory reconsolidation, reproducing the effect of general protein synthesis inhibition. Thus, Nader and colleagues demonstrated PKMζ inhibition and reconsolidation blockade disrupt in different ways the same molecular mechanism of memory maintenance - PKMζ inhibition erases all memories maintained in storage by the kinase; reconsolidation blockade disrupts specific recalled memories maintained by PKMζ by preventing resynthesis of the kinase after its degradation.
Topics: Protein Kinase C; Memory; Memory, Long-Term; Synaptic Transmission; Long-Term Potentiation
PubMed: 36739095
DOI: 10.1016/j.brainresbull.2023.02.001 -
Neuroscience and Biobehavioral Reviews Sep 2022Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder in which traumatic memories result in flashbacks and nightmares. With one-third of patients not... (Review)
Review
Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder in which traumatic memories result in flashbacks and nightmares. With one-third of patients not responding to standard exposure-based psychotherapy, new treatment strategies are needed. Sleep offers a unique time window to enhance therapeutic efficacy. Traumatic memories that are neutralized in therapy need to be stored back into memory (consolidated) during sleep to solidify the treatment effect. New basic research shows that memory consolidation can be enhanced by presenting sounds or scents that were linked to the memory at encoding, again during sleep. This procedure, termed targeted memory reactivation (TMR), has, despite its clinical potential, not been tested in (PTSD) patients. In this narrative review, we explore the potential of TMR as a new sleep-based treatment for PTSD. First we provide the necessary background on the memory and sleep principles underlying PTSD as well as the present applications and conditional factors of TMR. Then, we will discuss the outstanding questions and most promising experimental avenues when testing TMR to treat traumatic memories.
Topics: Humans; Memory; Memory Consolidation; Sleep; Stress Disorders, Post-Traumatic
PubMed: 35803396
DOI: 10.1016/j.neubiorev.2022.104765 -
Trends in Cognitive Sciences Apr 2024How do passing moments turn into lasting memories? Sheltered from external tasks and distractions, sleep constitutes an optimal state for the brain to reprocess and... (Review)
Review
How do passing moments turn into lasting memories? Sheltered from external tasks and distractions, sleep constitutes an optimal state for the brain to reprocess and consolidate previous experiences. Recent work suggests that consolidation is governed by the intricate interaction of slow oscillations (SOs), spindles, and ripples - electrophysiological sleep rhythms that orchestrate neuronal processing and communication within and across memory circuits. This review describes how sequential SO-spindle-ripple coupling provides a temporally and spatially fine-tuned mechanism to selectively strengthen target memories across hippocampal and cortical networks. Coupled sleep rhythms might be harnessed not only to enhance overnight memory retention, but also to combat memory decline associated with healthy ageing and neurodegenerative diseases.
Topics: Humans; Memory Consolidation; Electroencephalography; Sleep; Memory; Hippocampus
PubMed: 38443198
DOI: 10.1016/j.tics.2024.02.002 -
Philosophical Transactions of the Royal... Nov 1997A leading model for studying how the brain forms memories about unpleasant experiences is fear conditioning. A cumulative body of work has identified major components of... (Review)
Review
A leading model for studying how the brain forms memories about unpleasant experiences is fear conditioning. A cumulative body of work has identified major components of the neural system mediating this form of learning. The pathways involve transmission of sensory information from processing areas in the thalamus and cortex to the amygdala. The amygdala's lateral nucleus receives and integrates the sensory inputs from the thalamic and cortical areas, and the central nucleus provides the interface with motor systems controlling specific fear responses in various modalities (behavioural, autonomic, endocrine). Internal connections within the amygdala allow the lateral and central nuclei to communicate. Recent studies have begun to identify some sites of plasticity in the circuitry and the cellular mechanisms involved in fear conditioning. Through studies of fear conditioning, our understanding of emotional memory is being taken to the level of cells and synapses in the brain. Advances in understanding emotional memory hold out the possibility that emotional disorders may be better defined and treatment improved.
Topics: Animals; Brain; Fear; Humans; Memory; Psychopathology
PubMed: 9415924
DOI: 10.1098/rstb.1997.0154 -
ELife Jun 2022Two fundamental issues in memory research concern when later experiences strengthen or weaken initial memories and when the two memories become linked or remain...
Two fundamental issues in memory research concern when later experiences strengthen or weaken initial memories and when the two memories become linked or remain independent. A promising candidate for explaining these issues is semantic relatedness. Here, across five paired-associate learning experiments (N=1000), we systematically varied the semantic relatedness between initial and later cues, initial and later targets, or both. We found that learning retroactively benefited long-term memory performance for semantically related words (vs. unshown control words), and these benefits increased as a function of relatedness. Critically, memory dependence between initial and later pairs also increased with relatedness, suggesting that pre-existing semantic relationships promote interdependence for memories formed across episodes. We also found that modest retroactive benefits, but not interdependencies, emerged when subjects learned via studying rather than practice testing. These findings demonstrate that semantic relatedness during new learning retroactively strengthens old associations while scaffolding new ones into well-fortified memory traces.
Topics: Cues; Humans; Learning; Memory, Long-Term; Mental Recall; Semantics
PubMed: 35704025
DOI: 10.7554/eLife.72519