consolidation

Memory Decoding Journal Club: Systems consolidation reorganizes hippocampal engram circuitry

Systems consolidation reorganizes hippocampal engram circuitry

Memory Decoding Journal Club: Reconstructing a new hippocampal engram for systems reconsolidation and remote memory updating

Join us for the Memory Decoding Journal Club, a collaboration between the Carboncopies Foundation and BPF Aspirational Neuroscience. This month, we're diving into a groundbreaking paper: 'Reconstructing a new hippocampal engram for systems reconsolidation and remote memory updating' by Bo Lei, Bilin Kang, Yuejun Hao, Haoyu Yang, Zihan Zhong, Zihan Zhai, and Yi Zhong from Tsinghua University, Beijing Academy of Artificial Intelligence, IDG/McGovern Institute of Brain Research, and Peking Union Medical College. Dr. Randal Koene will guide us through an engaging discussion on these exciting findings and their implications for neuroscience and memory research.

Hippocampal sharp wave ripples for selection and consolidation of memories

Consolidation of remote contextual memory in the neocortical memory engram

Recent studies identified memory engram neurons, a neuronal population that is recruited by initial learning and is reactivated during memory recall.  Memory engram neurons are connected to one another through memory engram synapses in a distributed network of brain areas.  Our central hypothesis is that an associative memory is encoded and consolidated by selective strengthening of engram synapses.  We are testing this hypothesis, using a combination of engram cell labeling, optogenetic/chemogenetic, electrophysiological, and virus tracing approaches in rodent models of contextual fear conditioning.  In this talk, I will discuss our findings on how synaptic plasticity in memory engram synapses contributes to the acquisition and consolidation of contextual fear memory in a distributed network of the amygdala, hippocampus, and neocortex.

Mechanisms Underlying the Persistence of Cancer-Related Fatigue

Cancer-related fatigue is a prominent and debilitating side effect of cancer and its treatment. It can develop prior to diagnosis, generally peaks during cancer treatment, and can persist long after treatment completion. Its mechanisms are multifactorial, and its expression is highly variable. Unfortunately, treatment options are limited. Our research uses syngeneic murine models of cancer and cisplatin-based chemotherapy to better understand these mechanisms. Our data indicate that both peripherally and centrally processes may contribute to the developmental of fatigue. These processes include metabolic alterations, mitochondrial dysfunction, pre-cachexia, and inflammation. However, our data has revealed that behavioral fatigue can persist even after the toxicity associated with cancer and its treatment recover. For example, running during cancer treatment attenuates kidney toxicity while also delaying recovery from fatigue-like behavior. Additionally, administration of anesthetics known to disrupt memory consolidation at the time treatment can promote recovery, and treatment-related cues can re-instate fatigue after recovery. Cancer-related fatigue can also promote habitual behavioral patterns, as observed using a devaluation task. We interpret this data to suggest that limit metabolic resources during cancer promote the utilization of habit-based behavioral strategies that serve to maintain fatigue behavior into survivorship. This line of work is exciting as it points us toward novel interventional targets for the treatment of persistent cancer-related fatigue.

Targeting Maladaptive Emotional Memories to Treat Mental Health Disorders: Insights from Rodent Models

Maladaptive emotional memories contribute to the persistence of numerous mental health disorders, including post-traumatic stress disorder (PTSD), drug addiction and obsessive-compulsive disorder (OCD). Using rodent behavioural models of the psychological processes relevant to these disorders, it is possible to identify potential treatment targets for the development of new therapies, including those based upon disrupting the reconsolidation of maladaptive emotional memories. Using examples from rodent models relevant to multiple mental health disorders, this talk will consider some of the opportunities and challenges that this approach provides.

A biologically plausible inhibitory plasticity rule for world-model learning in SNNs

Memory consolidation is the process by which recent experiences are assimilated into long-term memory. In animals, this process requires the offline replay of sequences observed during online exploration in the hippocampus. Recent experimental work has found that salient but task-irrelevant stimuli are systematically excluded from these replay epochs, suggesting that replay samples from an abstracted model of the world, rather than verbatim previous experiences. We find that this phenomenon can be explained parsimoniously and biologically plausibly by a Hebbian spike time-dependent plasticity rule at inhibitory synapses. Using spiking networks at three levels of abstraction–leaky integrate-and-fire, biophysically detailed, and abstract binary–we show that this rule enables efficient inference of a model of the structure of the world. While plasticity has previously mainly been studied at excitatory synapses, we find that plasticity at excitatory synapses alone is insufficient to accomplish this type of structural learning. We present theoretical results in a simplified model showing that in the presence of Hebbian excitatory and inhibitory plasticity, the replayed sequences form a statistical estimator of a latent sequence, which converges asymptotically to the ground truth. Our work outlines a direct link between the synaptic and cognitive levels of memory consolidation, and highlights a potential conceptually distinct role for inhibition in computing with SNNs.

Active sleep in flies: the dawn of consciousness

The brain is a prediction machine. Yet the world is never entirely predictable, for any animal. Unexpected events are surprising and this typically evokes prediction error signatures in animal brains. In humans such mismatched expectations are often associated with an emotional response as well. Appropriate emotional responses are understood to be important for memory consolidation, suggesting that valence cues more generally constitute an ancient mechanism designed to potently refine and generalize internal models of the world and thereby minimize prediction errors. On the other hand, abolishing error detection and surprise entirely is probably also maladaptive, as this might undermine the very mechanism that brains use to become better prediction machines. This paradoxical view of brain functions as an ongoing tug-of-war between prediction and surprise suggests a compelling new way to study and understand the evolution of consciousness in animals. I will present approaches to studying attention and prediction in the tiny brain of the fruit fly, Drosophila melanogaster. I will discuss how an ‘active’ sleep stage (termed rapid eye movement – REM – sleep in mammals) may have evolved in the first animal brains as a mechanism for optimizing prediction in motile creatures confronted with constantly changing environments. A role for REM sleep in emotional regulation could thus be better understood as an ancient sleep function that evolved alongside selective attention to maintain an adaptive balance between prediction and surprise. This view of active sleep has some interesting implications for the evolution of subjective awareness and consciousness.

Imaging memory consolidation in wakefulness and sleep

New memories are initially labile and have to be consolidated into stable long-term representations. Current theories assume that this is supported by a shift in the neural substrate that supports the memory, away from rapidly plastic hippocampal networks towards more stable representations in the neocortex. Rehearsal, i.e. repeated activation of the neural circuits that store a memory, is thought to crucially contribute to the formation of neocortical long-term memory representations. This may either be achieved by repeated study during wakefulness or by a covert reactivation of memory traces during offline periods, such as quiet rest or sleep. My research investigates memory consolidation in the human brain with multivariate decoding of neural processing and non-invasive in-vivo imaging of microstructural plasticity. Using pattern classification on recordings of electrical brain activity, I show that we spontaneously reprocess memories during offline periods in both sleep and wakefulness, and that this reactivation benefits memory retention. In related work, we demonstrate that active rehearsal of learning material during wakefulness can facilitate rapid systems consolidation, leading to an immediate formation of lasting memory engrams in the neocortex. These representations satisfy general mnemonic criteria and cannot only be imaged with fMRI while memories are actively processed but can also be observed with diffusion-weighted imaging when the traces lie dormant. Importantly, sleep seems to hold a crucial role in stabilizing the changes in the contribution of memory systems initiated by rehearsal during wakefulness, indicating that online and offline reactivation might jointly contribute to forming long-term memories. Characterizing the covert processes that decide whether, and in which ways, our brains store new information is crucial to our understanding of memory formation. Directly imaging consolidation thus opens great opportunities for memory research.

Neural mechanisms for memory and emotional processing during sleep

The hippocampus and the amygdala are two structures required for emotional memory. While the hippocampus encodes the contextual part of the memory, the amygdala processes its emotional valence. During Non-REM sleep, the hippocampus displays high frequency oscillations called “ripples”. Our early work shows that the suppression of ripples during sleep impairs performance on a spatial task, underlying their crucial role in memory consolidation. We more recently showed that the joint amygdala-hippocampus activity linked to aversive learning is reinstated during the following Non-REM sleep epochs, specifically during ripples. This mechanism potentially sustains the consolidation of aversive associative memories during Non REM sleep. On the other hand, REM sleep is associated with regular 8 Hz theta oscillations, and is believed to play a role in emotional processing. A crucial, initial step in understanding this role is to unravel sleep dynamics related to REM sleep in the hippocampus-amygdala network

Herbert Jasper Lecture

There is a long-standing tension between the notion that the hippocampal formation is essentially a spatial mapping system, and the notion that it plays an essential role in the establishment of episodic memory and the consolidation of such memory into structured knowledge about the world. One theory that resolves this tension is the notion that the hippocampus generates rather arbitrary 'index' codes that serve initially to link attributes of episodic memories that are stored in widely dispersed and only weakly connected neocortical modules. I will show how an essentially 'spatial' coding mechanism, with some tweaks, provides an ideal indexing system and discuss the neural coding strategies that the hippocampus apparently uses to overcome some biological constraints affecting the possibility of shipping the index code out widely to the neocortex. Finally, I will present new data suggesting that the hippocampal index code is indeed transferred to layer II-III of the neocortex.

Spatiotemporal patterns of neocortical activity around hippocampal sharp-wave ripples

Neocortical-hippocampal interactions during off-line periods such as slow-wave sleep are implicated in memory processing. In particular, recent memory traces are replayed in hippocampus during some sharp-wave ripple (SWR) events, and these replay events are positively correlated with neocortical memory trace reactivation. A prevalent model is that SWR arise ‘spontaneously’ in CA3 and propagate recent memory ‘indices’ outward to the neocortex to enable memory consolidation there; however, the spatiotemporal distribution of neocortical activation relative to SWR is incompletely understood. We used wide-field optical imaging to study voltage and glutamate release transients in dorsal neocortex in relation to CA1 multiunit activity (MUA) and SWR of sleeping and urethane anesthetized mice. Modulation of voltage and glutamate release signals in relation to SWRs varied across superficial neocortical regions, and it was largest in posteromedial regions surrounding retrosplenial cortex (RSC), which receives strong hippocampal output connections. Activity tended to spread sequentially from more medial towards more lateral regions. Contrary to the unidirectional hypothesis, activation exhibited a continuum of timing relative to SWRs, varying from neocortex leading to neocortex lagging the SWRs (± ~250 msec). The timing continuum was correlated with the skewness of peri-SWR hippocampal MUA and with a tendency for some SWR to occur in clusters. Thus, contrary to the model in which SWRs arise spontaneously in hippocampus, neocortical activation often precedes SWRs and may thus constitute a trigger event in which neocortical information seeds associative reactivation of hippocampal ‘indices’.

Coordinated hippocampal-thalamic-cortical communication crucial for engram dynamics underneath systems consolidation

Understanding how a hippocampal inhibitory microcircuit contributes to memory consolidation and generalization

Astrocytes contribute to remote memory formation by modulating hippocampal-cortical communication during learning

How is it that some memories fade in a day while others last forever? The formation of long-lasting (remote) memories depends on the coordinated activity between the hippocampus and frontal cortices, but the timeline of these interactions is debated. Astrocytes, star-shaped glial cells, sense and modify neuronal activity, but their role in remote memory is scarcely explored. We manipulated the activity of hippocampal astrocytes during memory acquisition and discovered it impaired remote, but not recent, memory retrieval. We also revealed a massive recruitment of cortical-projecting hippocampal neurons during memory acquisition, a process that is specifically inhibited by astrocytic manipulation. Finally, we directly inhibited this projection during memory acquisition to prove its necessity for the formation of remote memory. Our findings reveal that the foundation of remote memory can be established during acquisition with projection-specific effect of astrocytes.

Retrieval spikes: a dendritic mechanism for retrieval-dependent memory consolidation

Sleep features for memory consolidation and network building across the lifespan

The Role of Hippocampal Replay in Memory Consolidation

The hippocampus lies at the centre of a network of brain regions thought to support spatial and episodic memory. Place cells - the principal cell of the hippocampus, represent information about an animal’s spatial location. Yet, during rest and awake quiescence place cells spontaneously recapitulate past trajectories (‘replay’). Replay has been hypothesised to support systems consolidation – the stabilisation of new memories via maturation of complementary cortical memory traces. Indeed, in recent work we found place and grid cells, from the deep medial entorhinal cortex (dMEC, the principal cortical output region of the hippocampus), replayed coherently during rest periods. Importantly, dMEC grid cells lagged place cells by ~11ms; suggesting the coordination may reflect consolidation. Moreover, preliminary data shows that the dMEC-hippocampal coordination strengthens as an animal becomes familiar with a task and that it may be led by directionally modulated cells. Finally, on-going work, in my recently established lab, shows replay may represent the mechanism underlying the maturation of episodic/spatial memory in pre-weanling pups. Together, these results indicate replay may play a central role in ensuring the permanency of memories.

How sleep remodels the brain

50 years ago it was found that sleep somehow made memories better and more permanent, but neither sleep nor memory researchers knew enough about sleep and memory to devise robust, effective tests. Today the fields of sleep and memory have grown and what is now understood is astounding. Still, great mysteries remain. What is the functional difference between the subtly different slow oscillation vs the slow wave of sleep and do they really have opposite memory consolidation effects? How do short spindles (e.g. <0.5 s as in schizophrenia) differ in function from longer ones and are longer spindles key to integrating new memories with old? Is the nesting of slow oscillations together with sleep spindles and hippocampal ripples necessary? What happens if all else is fine but the neurochemical environment is altered? Does sleep become maladaptive and “cement” memories into the hippocampal warehouse where they are assembled, together with all of their emotional baggage? Does maladaptive sleep underlie post-traumatic stress disorder and other stress-related disorders? How do we optimize sleep characteristics for top emotional and cognitive function? State of the art findings and current hypotheses will be presented.

A TIME WINDOW FOR MEMORY CONSOLIDATION DURING NREM SLEEP REVEALED BY CAMP OSCILLATION

FENS Forum 2026

DISTINCT ROLES OF HIPPOCAMPAL AND CORTICAL ENGRAMS IN REMOTE MEMORY CONSOLIDATION

FENS Forum 2026

LAYER-1 NDNF+ INTERNEURONS MEDIATE THE INTEGRATION OF SLEEP OSCILLATIONS CRITICAL FOR MEMORY CONSOLIDATION

FENS Forum 2026

THE ROLE OF SLEEP IN THE LONG-TERM CONSOLIDATION OF INFANT SPATIAL MEMORIES

FENS Forum 2026

UNDERSTAND THE ROLE OF HIPPOCAMPAL- THALAMIC-CORTICAL COORDINATION IN MEMORY CONSOLIDATION

FENS Forum 2026

MODULATION OF BEHAVIORAL TAGGING–MEDIATED MEMORY CONSOLIDATION AND SYNAPTIC PLASTICITY BY AMYLOID BETA<S>​</S>

FENS Forum 2026

TEMPORAL DYNAMICS OF CONSOLIDATION AND TASK INTERFERENCE IN TACTILE PERCEPTUAL LEARNING

FENS Forum 2026

SYSTEMS MEMORY CONSOLIDATION AS AN ANTIDOTE TO REPRESENTATIONAL DRIFT

FENS Forum 2026

A CLAUSTRAL PATHWAY LINKS HIPPOCAMPAL AND CORTICAL RHYTHMS TO SUPPORT SLEEP-DEPENDENT MEMORY CONSOLIDATION

FENS Forum 2026

SCHEMA MEMORY CONSOLIDATION IS HIPPOCAMPAL DEPENDENT

FENS Forum 2026

BALANCING GOOD AND BAD: SEROTONIN SIGNALS BIAS MEMORY CONSOLIDATION TOWARDS POSITIVE OR NEGATIVE EXPERIENCES

FENS Forum 2026

NEURONAL MECHANISMS OF LATE-PHASE CONSOLIDATION UNDERLYING MEMORY PERSISTENCE

FENS Forum 2026

NT3-TRKC SIGNALLING DISRUPTS FEAR MEMORY RECONSOLIDATION AND GLUTAMATE RECEPTOR REORGANIZATION

FENS Forum 2026

ROLE OF HIPPOCAMPO-PREFRONTAL CIRCUITS IN FEAR MEMORY CONSOLIDATION

FENS Forum 2026

MDMA ENHANCES RECONSOLIDATION-BASED INTERVENTIONS TO REDUCE ALCOHOL RELAPSE

FENS Forum 2026

ACUTE CORTICOSTERONE ALTERS FEAR MEMORY CONSOLIDATION AND EXTINCTION IN RODENTS​

FENS Forum 2026

THE REUNIENS NUCLEUS OF THE THALAMUS: THE CORNERSTONE OF BEHAVIORAL FLEXIBILITY AND SPATIAL MEMORY CONSOLIDATION IN RATS

FENS Forum 2026

RESTING-STATE OSCILLATORY SIGNATURES OF SUCCESSFUL FEAR MEMORY CONSOLIDATION

FENS Forum 2026

THC DISRUPTS MEMORY CONSOLIDATION VIA GLUTAMATERGIC DYSREGULATION IN THE HIPPOCAMPAL CA1 REGION

FENS Forum 2026

MTORC1 SIGNALING IN INSTRUMENTAL COCAINE- AND HEROIN- MEMORY RECONSOLIDATION IN RATS

FENS Forum 2026

NUCLEUS ACCUMBENS CONTROL OF VTA MODULATION OF HIPPOCAMPAL MEMORY CONSOLIDATION

FENS Forum 2026

CLOSED-LOOP INFRALIMBIC CORTEX STIMULATION REDUCES ANXIETY AND PREVENTS FEAR GENERALIZATION DURING MEMORY CONSOLIDATION AND RECONSOLIDATION

FENS Forum 2026

LONG-RANGE GABAERGIC PROJECTION NEURONS IN CA1 ORCHESTRATE STATE-DEPENDENT HIPPOCAMPAL-CORTICAL RHYTHMS SUPPORTING MEMORY CONSOLIDATION DURING RAPID EYE MOVEMENT SLEEP

FENS Forum 2026

PROTOCOL-DEPENDENT EFFECTS OF INFRALIMBIC LACTATE SIGNALING ON COCAINE MEMORY: EXTINCTION VERSUS RECONSOLIDATION

FENS Forum 2026

SYSTEMS CONSOLIDATION MECHANISM OF SOCIAL MEMORY IN MICE

FENS Forum 2026

RECONSOLIDATION-DEPENDENT UPDATING OF SOCIAL MEMORY IN VENTRAL HIPPOCAMPAL CA1

FENS Forum 2026

SLEEP-DEPENDENT MOTOR MEMORY CONSOLIDATION: ROLE OF CONSCIOUS AWARENESS OF ACTIONS

FENS Forum 2026

Think twice before you keep yourself awake!: The effects of two different sleep deprivation methods on the memory consolidation of object-location memories

Targeted memory reactivation during post-learning sleep affects memory consolidation within changes of dendritic spine plasticity

Distinct roles of prefrontal cortex subregions in the consolidation and recall of remote spatial memories

Synapse-Specific Homo- and Hetero-synaptic LTP-induced Memory Consolidation in The Amygdala

Study of synaptic plasticity mechanisms underlying memory consolidation in the hippocampo-neocortical network

Dissociable roles of sleep stages in the emergence and consolidation of transitive inference

Distinct Fos- and Npas4-mediated synaptic plasticity crucial for memory consolidation

COSYNE 2023

Stress-induced modulation of memory consolidation in the hippocampus-amygdala network during sleep

Silent epileptic activities: the missing link between Alzheimer’s disease, disrupted sleep and dysfunctional memory consolidation?

Differences in population sparsity can explain different memory consolidation speeds

The role of Transient Receptor Potential channels in memory consolidation in the passive avoidance task learning model in one-day old chicks

The role of noradrenaline in sleep-dependent memory consolidation

Dentate gyrus inhibitory microcircuit promotes network mechanisms underlying memory consolidation