Memory interference is a common cause of forgetting. Interference is a byproduct of the need to balance the formation of well-differentiated representations against the ability to retrieve memories from cues that are not identical to the original experience. How the brain accomplishes this has remained elusive. Here we review how insights can be gained from studies of an apparently unrelated phenomenon in the rodent brain--remapping in hippocampal place cells. Remapping refers to the formation of distinct representations in populations of place cells after minor changes in inputs to the hippocampus. Remapping might reflect processes involved generally in decorrelation of overlapping signals. These processes might be crucial for storing large numbers of similar experiences with only minimal interference.

Although the biochemical signaling events in area CA1 of the hippocampus underlying memory acquisition, consolidation, retrieval, and extinction have been extensively studied, little is known about the activity dynamics of hippocampal neurons in CA1 during Pavlovian fear conditioning. Here, we use fiber-optic confocal microscopy coupled with the calcium indicator GCaMP6m to monitor neuron activity in freely moving mice during trace fear conditioning. We show that the activity of a group of CA1 neurons increases not only after the stimulus presentations, but also during the stimulus-free trace period when the conditioned mice exhibit a high level of freezing behavior. Therefore, we designate these cells “trace cells”. Interestingly, the activity of the trace cells increases in response to the conditioned stimuli during memory retrieval but diminishes during memory extinction. Importantly, the dynamics of neuron activity exhibit a high degree of correlation with the freezing behavior of the mice, suggesting that a neuronal ensemble responsible for encoding the trace fear memory is repeatedly reactivated during memory retrieval and later extinguished during memory extinction.

The quest to understand the memory engram has intrigued humans for centuries. Recent technological advances, including genetic labelling, imaging, optogenetic and chemogenetic techniques, have propelled the field of memory research forward. These tools have enabled researchers to create and erase memory components. While these innovative techniques have yielded invaluable insights, they often focus on specific elements of the memory trace. Genetic labelling may rely on a particular immediate early gene as a marker of activity, optogenetics may activate or inhibit one specific type of neuron, and imaging may capture activity snapshots in a given brain region at specific times. Yet, memories are multifaceted, involving diverse arrays of neuronal subpopulations, circuits, and regions that work in concert to create, store, and retrieve information. Consideration of contributions of both excitatory and inhibitory neurons, micro and macro circuits across brain regions, the dynamic nature of active ensembles, and representational drift is crucial for a comprehensive understanding of the complex nature of memory.

During offline brain states, such as sleep and memory consolidation, respiration coordinates hippocampal activity. However, the role of breathing during online memory traces remains unclear. Here, we show that respiration can be recruited during online memory encoding. Optogenetic manipulation was used to control activation of the primary inspiratory rhythm generator PreBötzinger complex (PreBötC) in transgenic mice. When intermittent PreBötC-induced apnea covered the object exploration time during encoding, novel object detection was impaired. Moreover, the mice did not exhibit freezing behavior during presentation of fear-conditioned stimuli (CS+) when PreBötC-induced apnea occurred at the exact time of encoding. This apnea did not evoke changes in CA3 cell ensembles between presentations of CS+ and conditioned inhibition (CS−), whereas in normal breathing, CS+ presentations produced dynamic changes. Our findings demonstrate that components of central respiratory activity (e.g., frequency) during online encoding strongly contribute to shaping hippocampal ensemble dynamics and memory performance.

Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning. Utilizing GRABNE and GRABDA sensors, in vivo fiber photometry, and two new mouse models of altered locus coeruleus norepinephrine (LC-NE) synthesis, we investigate norepinephrine (NE) and dopamine (DA) release dynamics in dorsal hippocampal CA1 during contextual fear conditioning. We report that aversive foot-shock increases both NE and DA release in dorsal CA1, while freezing behavior associated with recall of fear memory is accompanied by decreased release. Partial loss of LC-NE synthesis reveals that NE release dynamics are modulated by sex. Moreover, we find that recall of recent fear memory is sensitive to both partial and complete loss of LC-NE synthesis throughout prenatal and postnatal development, similar to prior observations of mice with global loss of NE synthesis beginning postnatally. In contrast, remote recall is compromised only by complete loss of LC-NE synthesis beginning prenatally. Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior, and highlight a complex relationship between genotype, sex, and NE signaling.

Memories involving the hippocampus can take several days to consolidate, challenging efforts to uncover the neuronal signatures underlying this process. Here, we use calcium imaging in freely moving mice to track the hippocampal dynamics underlying memory consolidation across a 10-day contextual fear conditioning task. We find two neural signatures that emerge following learning and predict memory performance: context-specific place field remapping and coordinated neural activity prior to memory recall (freezing). To test whether these signatures support memory consolidation, we pharmacologically induced amnesia in separate mice by administering anisomycin, a protein synthesis inhibitor, immediately following learning. We find that anisomycin paradoxically accelerates cell turnover. Anisomycin also arrests learning-related remapping and blocks coordinated activity predictive of memory-related freezing behavior, effects that are likewise absent in untreated mice that exhibit poor memory expression. We conclude that context-specific place field remapping and the development of coordinated ensemble activity underlie contextual memory consolidation.

Abstract The partial reinforcement extinction effect (PREE) is a paradoxical learning phenomenon in which omission of reinforcement during acquisition results in more persistent conditioned responding in extinction. Here, we report a significant PREE with an inverted-U, entropy-like distribution against reinforcement probability following tone foot shock fear conditioning in rats, which was associated with increased neural activity in hippocampus and amygdala as indexed by p-ERK and c-fos immunolabelling. In vivo electrophysiological recordings of local field potentials (LFPs) showed that 50% reinforcement was associated with increases in the frequency and power of tone-evoked theta oscillations in both the subiculum region of hippocampus and in basolateral amygdala (BLA) during both acquisition (Day 1) and extinction (Day 2) sessions. Tone-evoked LFPs in 50% reinforced animals also showed increases in coherence and bidirectional Granger Causality between hippocampus and amygdala. The results support a Bayesian interpretation of the PREE, in which the phenomenon is driven by increases in the entropy or uncertainty of stimulus contingencies, and indicate a crucial role for hippocampus in mediating this uncertainty-dependent effect.

Threatening events and stressful experiences can lead to maladaptive memories and related behaviors. Existing treatments often fail to address these issues linked to anxiety/stress-related disorders effectively. This review identifies dose ranges associated with specific actions across various psychedelics. We examined psilocybin/psilocin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), mescaline, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), serotonin 2 A/2 C agonists (e.g., DOI) and 3,4-methylenedioxymethamphetamine (MDMA) on aversive memory extinction and reconsolidation, learned fear, anxiety, and locomotion in rodents. Nearly 400 studies published since 1957 were reviewed. Psychedelics often show biphasic effects on locomotion at doses that enhance extinction learning/retention, impair memory reconsolidation, or reduce learned fear and anxiety. Emerging evidence suggests a dissociation between their prospective benefits and locomotor effects. Under-explored aspects include sex differences, susceptibility to interference as memories age and generalize, repeated treatments, and immediate vs. delayed changes. Validating findings in traumatic-like memory and maladaptive fear/anxiety models is essential. Understanding how psychedelics modulate threat responses and post-retrieval memory processes in rodents may inform drug development and human studies, improving therapeutic approaches for related psychiatric conditions.

d a remapping index that indicates whether a given activity vector is closer to that at the beginning or end of the consolidation period. This remapping index ranges from −1 to 1; a value of 1 indicates a perfect match to the first bin of the consolidation period, a value of −1 indicates a perfect match to the last bin, and a value of 0 indicates equidistance from both. Remapping indices were strongly correlated with time, indicating that ABN activity gradually remapped during the consolidation period ( Figure 3 B). This remapping was detected, regardless of whether mice were awake or asleep ( Figure 3 B). It was not possible to calculate remapping indices during REM sleep given the limited amount of REM sleep during the consolidation period (<10% of total time) and the sparse activity of ABNs during this sleep stage (<6% of total ABN activity occurs in REM sleep) [ 16 ]. Figure 3. Open in a new tab ABN activity remapping during fear memory consolidation. ( A ) Activity vectors during memory consolidation (15 min bins). To represent data in the same range, the maximum activity of each neuron was scaled to 1. ( B ) Remapping index relative to the first and last activity vectors shown in ( A ). All, r = −0.97 p < 0.0001 slope = −0.0114; sleep, r = −0.98 p < 0.0001 slope = −0.0090; wake, r = −0.93 p = 0.008 slope = −0.0109. ( C ) Changes in ABN activity were correlated with time (Pearson’s correlation, p < 0.05; adjusted by false discovery rate, q < 0.05). ( D ) Pie chart of ABNs showing decreasing, increasing, or no change (i.e., non-remapping) in activity over time. ( E ) Mean activity of remapping and non-remapping ABNs during learning (preS and postS, averaged), consolidation, and test periods. Means were calculated after scaling activity vectors. * p < 0.05 between red and blue bars (bootstrap). ( F ) Similarity matrix between remapping and non-remapping ABNs. Significant clusters (red lines; hierarchical clustering, p < 0.05) were found on

mouse causes the mouse to have a long-term memory and fear of the location in which it occurred. Contextual fear conditioning causes hundreds of DSBs Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, it would be impossible for language, relationships, or personal identity to develop. Memory loss is usually described as forgetfulness or a disorder such as am The storage in sensory memory and short-term memory generally has a strictly limited capacity and duration. This means that information is not retained indefinitely. By contrast, while the total capacity of long-term memory has yet to be established, it can store much larger quantities of information. Furthermore, it can store this information for a much longer duration, potentially for a whole life span. For example, given a random seven-digit number, one may remember it for only a few seconds before forgetting, suggesting it was stored in short-term memory. On the other hand, one can remember telephone numbers for many years through repetition; this information is said to be stored in long-term memory. While short-term memory encodes information acoustically, long-term memory encodes it semantically: Baddeley (1966) discovered that, after 20 minutes, test subjects had the most difficulty recalling a collection of words that had similar meanings (e.g. big, large, great, huge) long-term. Another part of long-term memory is episodic memory, "which attempts to capture information such as 'what', 'when' and 'where'". With episodic memory, individuals are able to recall specific events such as birthday parties and weddings. Short-term memory is supported by transient patterns of neuronal communication, dependent on regions of the frontal lobe (especially dorsolateral prefrontal cortex) and the parietal lobe. Long-term memory, on the other hand, is maintained by more stable and permanent changes in neural connections widely spread throughout the brain. The hippocampus is essential (for learning new information) to the consolidation of information from short-term to long-term memory, although it does not seem to store information itself. It was thought that without the hippocampus new memories were unable to be stored into long-term memory and that there would be a very short attention span, as first gleaned from patient Henry Molaison after what was thought to be the full removal of both his hippocampi. More recent examination of his brain, post-mortem, shows that the hippocampus was more intact than first thought, throwing theories drawn from the initial data into…

general disorientation is linked to a remapping process: the firing fields of hippocampal place cells are suddenly … A model of hippocampal—cortical-amygdala interactions based on contextual fear conditioning 83 Brian Wiltgen … and John O’Keefe vi CONTENTS 12 ie) 16 Hippocampal remapping: implications for spatial learning and navigation

Plasticity in Pavlovian Fear Conditioning Stephen Maren 4 Plasticity of the Hippocampal Cellular Representation … Insights From Hippocampal Place Fields. Recordings of the place field properties of hippocampal neurons have … rat hippocampal slices. Neurosci. Lett. 96: 96-101. Rolls, E.T. (1996). A theory of hippocampal function