Initial Memory Consolidation Research Articles

Increased cortical inhibition following brief motor memory reactivation supports reconsolidation and overnight offline learning gains.

Practicing motor skills stabilizes and strengthens motor memories by repeatedly reactivating and reconsolidating them. The conventional view, by which a repetitive practice is required for substantially improving skill performance, has been recently challenged by behavioral experiments, in which even brief reactivations of the motor memory have led to significant improvements in skill performance. However, the mechanisms which facilitate brief reactivation-induced skill improvements remain elusive. While initial memory consolidation has been repeatedly associated with increased neural excitation and disinhibition, reconsolidation has been shown to involve a poorly understood mixture of both excitatory and inhibitory alterations. Here, we followed a 3-d reactivation-reconsolidation framework to examine whether the excitatory/inhibitory mechanisms which underlie brief reactivation and repetitive practice differ. Healthy volunteers practiced a motor sequence learning task using either brief reactivation or repetitive practice and were assessed using ultrahigh field (7T) magnetic resonance spectroscopy at the primary motor cortex (M1). We found that increased inhibition (GABA concentrations) and decreased excitation/inhibition (glutamate/GABA ratios) immediately following the brief reactivation were associated with overnight offline performance gains. These gains were on par with those exhibited following repetitive practice, where no correlations with inhibitory or excitatory changes were observed. Our findings suggest that brief reactivation and repetitive practice depend on fundamentally different neural mechanisms and that early inhibition-and not excitation-is particularly important in supporting the learning gains exhibited by brief reactivation.

Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study

Novelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates must be identified. In this cross-species study, we used a contextual novelty-exploration paradigm to identify changes in gene expression in the dorsal hippocampus of both mice and rats. We found that changes in gene expression following contextual novelty varied between the two species, with 9 genes being upregulated in mice and 3 genes in rats. Comparison across species revealed that ArfGAP with a GTPase domain, an ankyrin repeat and PH domain 3 (Agap3) was the only gene being upregulated in both, suggesting a potentially conserved role for Agap3. AGAP3 is known to regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor trafficking in the synapse, which suggests that increased transcription of Agap3 may be involved in maintaining functional plasticity. While we identified several genes affected by contextual novelty exploration, we were unable to fully reverse these changes using SCH 23390, a dopamine D1/D5 receptor antagonist. Further research on the role of AGAP3 in novelty-induced memory consolidation could lead to better understanding of this process and guide future research.

Hippocampal–cortical coupling differentiates long-term memory processes

Reactivation of long-term memories enables experience-dependent strengthening, weakening, or updating of memory traces. Although coupling of hippocampal and cortical activity patterns facilitates initial memory consolidation, whether and how these patterns are involved in postreactivation memory processes are not known. Here, we monitored the hippocampal-cortical network as rats repetitively learned and retrieved spatial and nonspatial memories. We show that interactions between hippocampal sharp wave-ripples (SPW-R), cortical spindles (SPI), and cortical ripples (CXR) are jointly modulated in the absence of memory demand but independently recruited depending on the stage of memory and task type. Reconsolidation of memory after retrieval is associated with an increased and extended window of coupling between hippocampal SPW-Rs and CXRs compared to the initial consolidation. Hippocampal SPW-R and cortical spindle interactions are preferentially engaged during memory consolidation. These findings suggest that specific, time-limited patterns of oscillatory coupling can support the distinct memory processes required to flexibly manage long-term memories in a dynamic environment.

Aloud real- time reading of intensive care unit diaries: A feasibility study

ObjectivesMemories of frightening/delusional intensive care unit experiences are a major risk factor for subsequent psychiatric morbidity of critical illness survivors; factual memories are protective. Systematically providing factual information during initial memory consolidation could mitigate the emotional character of the formed memories. We explored feasibility and obtained stakeholder feedback of a novel approach to intensive care unit diaries whereby entries were read aloud to the patients right after they were written to facilitate systematic real time orientation and formation of factual memories. Research methodologyProspective interventional pilot study involving reading diary entries aloud. We have also interviewed involved stakeholders for feedback and collected exploratory data on psychiatric symptoms from patients right after the intensive care stay. SettingVarious intensive care units in a single academic center. Main outcome measuresFeasibility was defined as intervention delivery on ≥80% of days following patient recruitment. Content analysis was performed on stakeholder interview responses. Questionnaire data were compared for patients who received real-time reading to the historical cohort who did not. ResultsOverall, 57% (17 of 30) of patients achieved the set feasibility threshold. Following protocol adjustment, we achieved 86% feasibility in the last subset of patients. Patients reported the intervention as comforting and appreciated the reorientation aspect. Nurses overwhelmingly liked the idea; most common concern was not knowing what to write. Some therapists were unsure whether reading entries aloud might overwhelm the patients. There were no significant differences in psychiatric symptoms when compared to the historic cohort. ConclusionWe encountered several implementation obstacles; once these were addressed, we achieved set feasibility target for the last group of patients. Reading diary entries aloud was welcomed by stakeholders. Designing a trial to assess efficacy of the intervention on psychiatric outcomes appears warranted. Implications for Clinical PracticeThere is no recommendation to change current practice as benefits of the intervention are unproven.

Can We Pick the Pocket of Post-Intensive Care Syndrome?

IntroductionPost-intensive care syndrome, which includes symptoms of anxiety, depression, and posttraumatic stress, afflicts one-third of critical illness survivors. Symptoms persist and significantly degrade quality of life. No intervention has earned clear evidence of reducing these adverse psychological sequelae. Building on earlier pilot data, psychological support based on positive suggestions (PSBPS), is being investigated in an ongoing, randomized, controlled prospective trial across multiple intensive care unit (ICU) settings in a large, tertiary medical center.ObjectivesRecognizing that even sedated patients perceive and internalize communication, we share lessons learned thus far in the art of engaging with sedated, often unresponsive patients.MethodsOur presentation describes this NIH-funded PSBPS study, including the preparatory training and subsequent implementation of a structured script delivered daily to ICU patients, regardless of cognitive status or ability to respond. To interfere with the initial process of fear conditioning/negative memory formation, we introduce mitigating information about potentially traumatic events during the temporal window when initial memory consolidation occurs, reframing the alien, often frightening ICU environment while providing positive suggestions of safety and healing.ResultsPsychiatrists characteristically engage alert, communicative patients. Unfortunately, when meaningful cognitive exchange is impossible, further effort is often limited. By contrast, choosing to engage ventilated, sedated patients with active re-interpretation is a novel enterprise. We share technique and lessons learned from the first two years.ConclusionsConsultation psychiatrists are uniquely situated to explore with our critical care colleagues how best to mitigate the corrosive psychological consequences of intensive care and improve the future of ICU survivors.DisclosureNo significant relationships.

Rpd3/CoRest-mediated activity-dependent transcription regulates the flexibility in memory updating in Drosophila

Consolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in memory consolidation, which is unexpectedly linked to the later memory updating in Drosophila. Through proteomic analysis, we discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd3 and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. Opening the gate through the compositional change in Rpd3/CoRest is required for memory consolidation, but closing the gate through Rpd3/CoRest is significant to limit future memory updating. Our data indicate that the flexibility of memory updating is determined through the initial activity-dependent transcription, providing a mechanism involved in defining memory state.

Initial memory consolidation and the synaptic tagging and capture hypothesis.

Everyday memories are retained automatically in the hippocampus and then decay very rapidly. Memory retention can be boosted when novel experiences occur shortly before or shortly after the time of memory encoding via a memory stabilization process called "initial memory consolidation." The dopamine release and new protein synthesis in the hippocampus during a novel experience are crucial for this novelty-induced memory boost. The mechanisms underlying initial memory consolidation are not well-understood, but the synaptic tagging and capture (STC) hypothesis provides a conceptual basis of synaptic plasticity events occurring during initial memory consolidation. In this review, we provide an overview of the STC hypothesis and its relevance to dopaminergic signalling, in order to explore the cellular and molecular mechanisms underlying initial memory consolidation in the hippocampus. We summarize electrophysiological STC processes based on the evidence from two-pathway experiments and a behavioural tagging hypothesis, which translates the STC hypothesis into a related behavioural hypothesis. We also discuss the function of two types of molecules, "synaptic tags" and "plasticity-related proteins," which have a crucial role in the STC process and initial memory consolidation. We describe candidate molecules for the roles of synaptic tag and plasticity-related proteins and interpret their candidacy based on evidence from two-pathway experiments ex vivo, behavioural tagging experiments in vivo and recent cutting-edge optical imaging experiments. Lastly, we discuss the direction of future studies to advance our understanding of molecular mechanisms underlying the STC process, which are critical for initial memory consolidation in the hippocampus.

Locus Coeruleus and Dopamine-Dependent Memory Consolidation.

Most everyday memories including many episodic-like memories that we may form automatically in the hippocampus (HPC) are forgotten, while some of them are retained for a long time by a memory stabilization process, called initial memory consolidation. Specifically, the retention of everyday memory is enhanced, in humans and animals, when something novel happens shortly before or after the time of encoding. Converging evidence has indicated that dopamine (DA) signaling via D1/D5 receptors in HPC is required for persistence of synaptic plasticity and memory, thereby playing an important role in the novelty-associated memory enhancement. In this review paper, we aim to provide an overview of the key findings related to D1/D5 receptor-dependent persistence of synaptic plasticity and memory in HPC, especially focusing on the emerging evidence for a role of the locus coeruleus (LC) in DA-dependent memory consolidation. We then refer to candidate brain areas and circuits that might be responsible for detection and transmission of the environmental novelty signal and molecular and anatomical evidence for the LC-DA system. We also discuss molecular mechanisms that might mediate the environmental novelty-associated memory enhancement, including plasticity-related proteins that are involved in initial memory consolidation processes in HPC.

Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal CA1 neurons during locomotor activity and sleep

The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1 single-unit and local field potential (LFP) activity in Arc/Arg3.1 knockout and wild-type mice during track running and flanking sleep periods. Locomotor activity, basic firing and spatial coding properties of CA1 cells in knockout mice were not different from wild-type mice. During active behavior, however, knockout animals showed a significantly shifted balance in LFP power, with a relative loss in high-frequency (beta-2 and gamma) bands compared to low-frequency bands. Moreover, during track-running, knockout mice showed a decrease in phase locking of spiking activity to LFP oscillations in theta, beta and gamma bands. Sleep architecture in knockout mice was not grossly abnormal. Sharp-wave ripples, which have been associated with memory consolidation and replay, showed only minor differences in dynamics and amplitude. Altogether, these findings suggest that Arc/Arg3.1 effects on memory formation are not only manifested at the level of molecular pathways regulating synaptic plasticity, but also at the systems level. The disrupted power balance in theta, beta and gamma rhythmicity and concomitant loss of spike-field phase locking may affect memory encoding during initial storage and memory consolidation stages.

Emotion Causes Targeted Forgetting of Established Memories

Reconsolidation postulates that reactivation of a memory trace renders it susceptible to disruption by treatments similar to those that impair initial memory consolidation. Despite evidence that implicit, or non-declarative, human memories can be disrupted at retrieval, a convincing demonstration of selective impairment in retrieval of target episodic memories following reactivation is lacking. In human subjects, we demonstrate that if reactivation of a verbal memory, through successful retrieval, is immediately followed by an emotionally aversive stimulus, a significant impairment is evident in its later recall. This effect is time-dependent and persists for at least 6 days. Thus, in line with a reconsolidation hypothesis, established human episodic memories can be selectively impaired following their retrieval.

Protein degradation, as with protein synthesis, is required during not only long‐term spatial memory consolidation but also reconsolidation

The formation of long-term memory requires protein synthesis, particularly during initial memory consolidation. This process also seems to be dependant upon protein degradation, particularly degradation by the ubiquitin-proteasome system. The aim of this study was to investigate the temporal requirement of protein synthesis and degradation during the initial consolidation of allocentric spatial learning. As memory returns to a labile state during reactivation, we also focus on the role of protein synthesis and degradation during memory reconsolidation of this spatial learning. Male CD1 mice were submitted to massed training in the spatial version of the Morris water maze. At various time intervals after initial acquisition or after a reactivation trial taking place 24 h after acquisition, mice received an injection of either the protein synthesis inhibitor anisomycin or the protein degradation inhibitor lactacystin. This injection was performed into the hippocampal CA3 region, which is specifically implicated in the processing of spatial information. Results show that, in the CA3 hippocampal region, consolidation of an allocentric spatial learning task requires two waves of protein synthesis taking place immediately and 4 h after acquisition, whereas reconsolidation requires only the first wave. However, for protein degradation, both consolidation and reconsolidation require only one wave, taking place immediately after acquisition or reactivation, respectively. These findings suggest that protein degradation is a key step for memory reconsolidation, as for consolidation. Moreover, as protein synthesis-dependent reconsolidation occurred faster than consolidation, reconsolidation did not consist of a simple repetition of the initial consolidation.

Brain processing of proper names

Proper names are of practical importance for verbal communication. For instance, they are indispensable for transmission of autobiographical information concerning a person. Recent studies have revealed that proper names are neuropsychologically and anatomically processed in a manner that differs from the processing of common nouns. The current review described proper names, which are labels attached to referents, as being without semantic meaning. The clinical data are presented regarding comprehension and retrieval of people's names, and memory of their unique properties. The validity of a cognitive neuropsychological model of people's name processing is also evaluated. The review suggests that after the initial memory consolidation of a name and a person by the left hemisphere's hippo/parahippocampus, the memory become established in the adjoining fusiform gyrus. Consequently, it is hypothesized that the fusiform gyrus forms a processing network for people's names with the temporal pole and postero temporo/occipital lobe. The research on geographical names, topographical names, and therapeutic approaches for deficits of proper names is also reviewed.