Conspecific interactions predict social transmission of fear in female rats.

Social transmission of fear occurs in a subset of individuals, where an Observer displays a fear response to a previously neutral stimulus after witnessing or interacting with a conspecific Demonstrator during memory retrieval. The conditions under which fear can be acquired socially in rats have received attention in recent years, and suggest that social factors modulate social transmission of information. We previously found that one such factor, social rank, impacts fear conditioning by proxy in male rats. Here, we aimed to investigate whether social roles as determined by nape contacts in females, might also have an influence on social transmission of fear. In-line with previous findings in males, we found that social interactions in the home cage can provide insight into the social relationship between female rats and that these relationships predict the degree of fear acquired by-proxy. These results suggest that play behavior affects the social transfer/transmission of information in female rats.

Neuroscience: Memory modification without catastrophe.

Adaptive behaviour is supported by changes in neuronal networks. Insight into maintaining these memories - preventing their catastrophic loss - despite further network changes occurring due to novel learning is provided in a new study.

It is a match! Timely response to a specific target boosts concurrent task processing.

Multitasking typically leads to interference. However, responding to attentionally demanding targets in a continuous task paradoxically enhances memory for concurrently presented images, known as the "attentional boost effect" (ABE). Previous research has attributed the ABE to a temporal orienting response induced by the release of norepinephrine from the locus coeruleus when a stimulus is classified as a target. In this study, we tested whether target classification and response decisions act in an all-or-none manner on the ABE, or whether the processes leading up to these decisions also modulate the ABE. Participants encoded objects into memory while monitoring a stream of letters and digits, pressing a key for target letters. To change the process leading to target classification, we asked participants to respond either to a specific target letter or an entire category of letters. To change the process leading to response, we asked participants to either respond immediately to the target or withhold the response until the appearance of the next stimulus. Despite successfully identifying the target and responding to it in all conditions, participants benefited less from target detection in category search than in exact search and less from delayed response than immediate response. These findings suggest that target and response decisions do not act in an all-or-none manner. Instead, the ABE and the temporal orienting response is sensitive to the speed of reaching a perceptual or response decision. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparing targeted memory reactivation during slow wave sleep and sleep stage 2.

Sleep facilitates declarative memory consolidation, which is assumed to rely on the reactivation of newly encoded memories orchestrated by the temporal interplay of slow oscillations (SO), fast spindles and ripples. SO as well as the number of spindles coupled to SO are more frequent during slow wave sleep (SWS) compared to lighter sleep stage 2 (S2). But, it is unclear whether memory reactivation is more effective during SWS than during S2. To test this question, we applied Targeted Memory Reactivation (TMR) in a declarative memory design by presenting learning-associated sound cues during SWS vs. S2 in a counterbalanced within-subject design. Contrary to our hypothesis, memory performance was not significantly better when cues were presented during SWS. Event-related potential (ERP) amplitudes were significantly higher for cues presented during SWS than S2, and the density of SO and SO-spindle complexes was generally higher during SWS than during S2. Whereas SO density increased during and after the TMR period, SO-spindle complexes decreased. None of the parameters were associated with memory performance. These findings suggest that the efficacy of TMR does not depend on whether it is administered during SWS or S2, despite differential processing of memory cues in these sleep stages.

The ventromedial prefrontal cortex in response to threat omission is associated with subsequent explicit safety memory.

In order to memorize and discriminate threatening and safe stimuli, the processing of the actual absence of threat seems crucial. Here, we measured brain activity with fMRI in response to both threat conditioned stimuli and their outcomes by combining threat learning with a subsequent memory paradigm. Participants (N = 38) repeatedly saw a variety of faces, half of which (CS+) were associated with an aversive unconditioned stimulus (US) and half of which were not (CS-). When an association was later remembered, the hippocampus had been more active (than when forgotten). However, the ventromedial prefrontal cortex predicted subsequent memory specifically during safe associations (CS- and US omission responses) and the left dorsolateral prefrontal cortex during outcomes in general (US and US omissions). In exploratory analyses of the theoretically important US omission, we found extended involvement of the medial prefrontal cortex and an enhanced functional connectivity to visual and somatosensory cortices, suggesting a possible function in sustaining sensory information for an integration with semantic memory. Activity in visual and somatosensory cortices together with the inferior frontal gyrus also predicted memory performance one week after learning. The findings imply the importance of a close interplay between prefrontal and sensory areas during the processing of safe outcomes-or 'nothing'-to establish declarative safety memory.

The mnemonic effect of central and peripheral misinformation on social media.

The increasing use of social media has amplified the spread of false information. Yet little is known about the mnemonic consequences associated with exposure to different types of false information online. In two studies, we examined in a simulated online context how exposure to false information either central or peripheral in events affected memory. European American and Asian/Asian American college students (Study 1 N = 200; Study 2 N = 225) were presented with GIFs of daily life events and read tweets about the events that included four types of information: central true information, central false information, peripheral true information, and peripheral false information. They then took a True/False recognition test that included tweeted and untweeted true and false information and indicated how confident they were in their responses. Regardless of cultural background, participants in both studies demonstrated the misinformation effect, whereby they falsely recognised more and resisted less tweeted than untweeted false information. Furthermore, they showed higher susceptibility to peripheral than central false information exposed via tweets. Asian participants were less influenced by misinformation than European Americans in Study 2. These findings have important implications to combat misinformation in online environments.

Identification of Early Hippocampal Dynamics during Recognition Memory with Independent Component Analysis.

The hippocampus is generally considered to have relatively late involvement in recognition memory, its main electrophysiological signature being between 400 and 800 ms after stimulus onset. However, most electrophysiological studies have analyzed the hippocampus as a single responsive area, selecting only a single-site signal exhibiting the strongest effect in terms of amplitude. These classical approaches may not capture all the dynamics of this structure, hindering the contribution of other hippocampal sources that are not located in the vicinity of the selected site. We combined intracerebral electroencephalogram recordings from epileptic patients with independent component analysis during a recognition memory task involving the recognition of old and new images. We identified two sources with different responses emerging from the hippocampus: a fast one (maximal amplitude at ∼250 ms) that could not be directly identified from raw recordings and a latter one, peaking at ∼400 ms. The former component presented different amplitudes between old and new items in 6 out of 10 patients. The latter component had different delays for each condition, with a faster activation (∼290 ms after stimulus onset) for recognized items. We hypothesize that both sources represent two steps of hippocampal recognition memory, the faster reflecting the input from other structures and the latter the hippocampal internal processing. Recognized images evoking early activations would facilitate neural computation in the hippocampus, accelerating memory retrieval of complementary information. Overall, our results suggest that the hippocampal activity is composed of several sources with an early activation related to recognition memory.

Overnight neuronal plasticity and adaptation to emotional distress.

Expressions such as 'sleep on it' refer to the resolution of distressing experiences across a night of sound sleep. Sleep is an active state during which the brain reorganizes the synaptic connections that form memories. This Perspective proposes a model of how sleep modifies emotional memory traces. Sleep-dependent reorganization occurs through neurophysiological events in neurochemical contexts that determine the fates of synapses to grow, to survive or to be pruned. We discuss how low levels of acetylcholine during non-rapid eye movement sleep and low levels of noradrenaline during rapid eye movement sleep provide a unique window of opportunity for plasticity in neuronal representations of emotional memories that resolves the associated distress. We integrate sleep-facilitated adaptation over three levels: experience and behaviour, neuronal circuits, and synaptic events. The model generates testable hypotheses for how failed sleep-dependent adaptation to emotional distress is key to mental disorders, notably disorders of anxiety, depression and post-traumatic stress with the common aetiology of insomnia.

A randomised controlled trial investigating the causal role of the medial prefrontal cortex in mediating self-agency during speech monitoring and reality monitoring.

Self-agency is the awareness of being the agent of one's own thoughts and actions. Self-agency is essential for interacting with the outside world (reality-monitoring). The medial prefrontal cortex (mPFC) is thought to be one neural correlate of self-agency. We investigated whether mPFC activity can causally modulate self-agency on two different tasks of speech-monitoring and reality-monitoring. The experience of self-agency is thought to result from making reliable predictions about the expected outcomes of one's own actions. This self-prediction ability is necessary for the encoding and memory retrieval of one's own thoughts during reality-monitoring to enable accurate judgments of self-agency. This self-prediction ability is also necessary for speech-monitoring where speakers consistently compare auditory feedback (what we hear ourselves say) with what we expect to hear while speaking. In this study, 30 healthy participants are assigned to either 10 Hz repetitive transcranial magnetic stimulation (rTMS) to enhance mPFC excitability (N = 15) or 10 Hz rTMS targeting a distal temporoparietal site (N = 15). High-frequency rTMS to mPFC enhanced self-predictions during speech-monitoring that predicted improved self-agency judgments during reality-monitoring. This is the first study to provide robust evidence for mPFC underlying a causal role in self-agency, that results from the fundamental ability of improving self-predictions across two different tasks.

Astrocytes control recent and remote memory strength by affecting the recruitment of the CA1→ACC projection to engrams.

The maturation of engrams from recent to remote time points involves the recruitment of CA1 neurons projecting to the anterior cingulate cortex (CA1→ACC). Modifications of G-protein-coupled receptor pathways in CA1 astrocytes affect recent and remote recall in seemingly contradictory ways. To address this inconsistency, we manipulated these pathways in astrocytes during memory acquisition and tagged c-Fos-positive engram cells and CA1→ACC cells during recent and remote recall. The behavioral results were coupled with changes in the recruitment of CA1→ACC projection cells to the engram: Gq pathway activation in astrocytes caused enhancement of recent recall alone and was accompanied by earlier recruitment of CA1→ACC projecting cells to the engram. In contrast, Gi pathway activation in astrocytes resulted in the impairment of only remote recall, and CA1→ACC projecting cells were not recruited during remote memory. Finally, we provide a simple working model, hypothesizing that Gq and Gi pathway activation affect memory differently, by modulating the same mechanism: CA1→ACC projection.

Perineuronal Nets in the CNS: Architects of Memory and Potential Therapeutic Target in Neuropsychiatric Disorders.

The extracellular matrix (ECM) within the brain possesses a distinctive composition and functionality, influencing a spectrum of physiological and pathological states. Among its constituents, perineuronal nets (PNNs) are unique ECM structures that wrap around the cell body of many neurons and extend along their dendrites within the central nervous system (CNS). PNNs are pivotal regulators of plasticity in CNS, both during development and adulthood stages. Characterized by their condensed glycosaminoglycan-rich structures and heterogeneous molecular composition, PNNs not only offer neuroprotection but also participate in signal transduction, orchestrating neuronal activity and plasticity. Interfering with the PNNs in adult animals induces the reactivation of critical period plasticity, permitting modifications in neuronal connections and promoting the recovery of neuroplasticity following spinal cord damage. Interestingly, in the adult brain, PNN expression is dynamic, potentially modulating plasticity-associated states. Given their multifaceted roles, PNNs have emerged as regulators in the domains of learning, memory, addiction behaviors, and other neuropsychiatric disorders. In this review, we aimed to address how PNNs contribute to the memory processes in physiological and pathological conditions.

Formation of memory assemblies through the DNA-sensing TLR9 pathway.

As hippocampal neurons respond to diverse types of information1, a subset assembles into microcircuits representing a memory2. Those neurons typically undergo energy-intensive molecular adaptations, occasionally resulting in transient DNA damage3-5. Here we found discrete clusters of excitatory hippocampal CA1 neurons with persistent double-stranded DNA (dsDNA) breaks, nuclear envelope ruptures and perinuclear release of histone and dsDNA fragments hours after learning. Following these early events, some neurons acquired an inflammatory phenotype involving activation of TLR9 signalling and accumulation of centrosomal DNA damage repair complexes6. Neuron-specific knockdown of Tlr9 impaired memory while blunting contextual fear conditioning-induced changes of gene expression in specific clusters of excitatory CA1 neurons. Notably, TLR9 had an essential role in centrosome function, including DNA damage repair, ciliogenesis and build-up of perineuronal nets. We demonstrate a novel cascade of learning-induced molecular events in discrete neuronal clusters undergoing dsDNA damage and TLR9-mediated repair, resulting in their recruitment to memory circuits. With compromised TLR9 function, this fundamental memory mechanism becomes a gateway to genomic instability and cognitive impairments implicated in accelerated senescence, psychiatric disorders and neurodegenerative disorders. Maintaining the integrity of TLR9 inflammatory signalling thus emerges as a promising preventive strategy for neurocognitive deficits.

Coupled sleep rhythms for memory consolidation.

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.

Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling.

Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an early life WD rodent model associated with long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style WD (ad libitum access to various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) during the juvenile and adolescent stages (postnatal days 26-56). Behavioral and metabolic assessments were performed both before and after a healthy diet intervention period beginning at early adulthood. Results revealed HPC-dependent contextual episodic memory impairments in CAF rats that persisted despite the healthy diet intervention. Given that dysregulated HPC acetylcholine (ACh) signaling is associated with memory impairments in humans and animal models, we examined protein markers of ACh tone in the dorsal HPC (HPCd) in CAF and CTL rats. Results revealed significantly lower protein levels of vesicular ACh transporter in the HPCd of CAF vs. CTL rats, indicating chronically reduced ACh tone. Using intensity-based ACh sensing fluorescent reporter (iAChSnFr) in vivo fiber photometry targeting the HPCd, we next revealed that ACh release during object-contextual novelty recognition was highly predictive of memory performance and was disrupted in CAF vs. CTL rats. Neuropharmacological results showed that alpha 7 nicotinic ACh receptor agonist infusion in the HPCd during training rescued memory deficits in CAF rats. Overall, these findings reveal a functional connection linking early life WD intake with long-lasting dysregulation of HPC ACh signaling, thereby identifying an underlying mechanism for WD-associated memory impairments.

Functionally refined encoding of threat memory by distinct populations of basal forebrain cholinergic projection neurons.

Neurons of the basal forebrain nucleus basalis and posterior substantia innominata (NBM/SIp) comprise the major source of cholinergic input to the basolateral amygdala (BLA). Using a genetically encoded acetylcholine (ACh) sensor in mice, we demonstrate that BLA-projecting cholinergic neurons can 'learn' the association between a naive tone and a foot shock (training) and release ACh in the BLA in response to the conditioned tone 24 hr later (recall). In the NBM/SIp cholinergic neurons express the immediate early gene, Fos following both training and memory recall. Cholinergic neurons that express Fos following memory recall display increased intrinsic excitability. Chemogenetic silencing of these learning-activated cholinergic neurons prevents expression of the defensive behavior to the tone. In contrast, we show that NBM/SIp cholinergic neurons are not activated by an innately threatening stimulus (predator odor). Instead, VP/SIa cholinergic neurons are activated and contribute to defensive behaviors in response to predator odor, an innately threatening stimulus. Taken together, we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli, demonstrating functionally refined organization of specific types of memory within the cholinergic basal forebrain of mice.

Exploring the Association between Amyloid-ß and Memory Markers for Alzheimer's Disease in Cognitively Unimpaired Older Adults.

BACKGROUND: Memory tests vary in their sensitivity for detection of pre-symptomatic Alzheimer's disease (AD). The Visual Short-Term Memory Binding Test (VSTMBT) identifies AD-related performance deficits in older adults who are otherwise cognitively unimpaired. OBJECTIVE: We investigated the association of this psychometric measure with brain amyloidosis and atrophy. DESIGN: Cross-sectional mixed and correlational. SETTING: Cognitive Reserve Study from Columbia University. PARTICIPANTS: a sample of 39 cognitively unimpaired older adults (Age: M=65.3, SD=3.07) was obtained from the above study. MEASUREMENTS: Extensive neuropsychological and neuroimaging (MRI and amyloid-ß PET) assessments were carried out. RESULTS: Performance on the VSTMBT allowed us to split the sample into Low Binding Cost (LBC, N=21) and High Binding Cost (HBC, N=18). Groups were matched according to age [p=0.702], years of education [0.071], and sex [p=0.291]. HBC's performance was comparable to that seen in symptomatic AD. Groups only differed in their amyloid-ß deposition on PET in regions of the right ventral stream linked to visual cognition and affected early in AD pathogenesis (lateral-occipital cortex, p = 0.008; fusiform gyrus, p = 0.017; and entorhinal cortex, p = 0.046). Other regions known to be linked to low-level visual integration function also revealed increased amyloid-ß deposition in HBC. CONCLUSIONS: VSTMB deficits are associated with neuropathogenesis (i.e., amyloid-ß deposition) in the earliest affected regions in pre-symptomatic AD. The VSTMB test holds potential for the identification of cognitively unimpaired older adults with very early AD pathogenesis and may thus be a useful tool for early intervention trials or other forms of clinical research.

A shared neural code for perceiving and remembering social interactions in the human superior temporal sulcus.

Recognizing and remembering social information is a crucial cognitive skill. Neural patterns in the superior temporal sulcus (STS) support our ability to perceive others' social interactions. However, despite the prominence of social interactions in memory, the neural basis of remembering social interactions is still unknown. To fill this gap, we investigated the brain mechanisms underlying memory of others' social interactions during free spoken recall of a naturalistic movie. By applying machine learning-based fMRI encoding analyses to densely labeled movie and recall data we found that a subset of the STS activity evoked by viewing social interactions predicted neural responses in not only held-out movie data, but also during memory recall. These results provide the first evidence that activity in the STS is reinstated in response to specific social content and that its reactivation underlies our ability to remember others' interactions. These findings further suggest that the STS contains representations of social interactions that are not only perceptually driven, but also more abstract or conceptual in nature.

Essential Role of Astrocytes in Learning and Memory.

One of the most biologically relevant functions of astrocytes within the CNS is the regulation of synaptic transmission, i.e., the physiological basis for information transmission between neurons. Changes in the strength of synaptic connections are indeed thought to be the cellular basis of learning and memory. Importantly, astrocytes have been demonstrated to tightly regulate these processes via the release of several gliotransmitters linked to astrocytic calcium activity as well as astrocyte-neuron metabolic coupling. Therefore, astrocytes seem to be integrators of and actors upon learning- and memory-relevant information. In this review, we focus on the role of astrocytes in learning and memory processes. We delineate the recognized inputs and outputs of astrocytes and explore the influence of manipulating astrocytes on behaviour across diverse learning paradigms. We conclude that astrocytes influence learning and memory in various manners. Appropriate astrocytic Ca2+ dynamics are being increasingly identified as central contributors to memory formation and retrieval. In addition, astrocytes regulate brain rhythms essential for cognition, and astrocyte-neuron metabolic cooperation is required for memory consolidation.

Proteomic-Based Studies on Memory Formation in Normal and Neurodegenerative Disease-Affected Brains.

A critical aspect of cognition is the ability to acquire, consolidate, and evoke memories, which is considerably impaired by neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. These mnemonic processes are dependent on signaling cascades, which involve protein expression and degradation. Recent mass spectrometry (MS)-based proteomics has opened a range of possibilities for the study of memory formation and impairment, making it possible to research protein systems not studied before. However, in the context of synaptic proteome related to learning processes and memory formation, a deeper understanding of the synaptic proteome temporal dynamics after induction of synaptic plasticity and the molecular changes underlying the cognitive deficits seen in neurodegenerative diseases is needed. This review analyzes the applications of proteomics for understanding memory processes in both normal and neurodegenerative conditions. Moreover, the most critical experimental studies have been summarized using the PANTHER overrepresentation test. Finally, limitations associated with investigations of memory studies in physiological and neurodegenerative disorders have also been discussed.

The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids.

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory models prior to the development of neuromuscular deficits that mirror human spastic paraplegia. Via pulldown-mass spectrometry analyses, we find that DDHD2 binds to the key synaptic protein STXBP1. Using STXBP1/2 knockout neurosecretory cells and a haploinsufficient STXBP1+/- mouse model of human early infantile encephalopathy associated with intellectual disability and motor dysfunction, we show that STXBP1 controls targeting of DDHD2 to the plasma membrane and generation of saturated FFAs in the brain. These findings suggest key roles for DDHD2 and STXBP1 in lipid metabolism and in the processes of synaptic plasticity, learning, and memory.