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Conditioned fear memories that are context-specific shortly after conditioning generalize over time. We exposed rats to a context reminder 30 d after conditioning, which served to reinstate context-specificity, and investigated how this reminder alters retrieval-induced activity in the hippocampus and anterior cingulate cortex (aCC) relative to a no reminder condition. c-Fos expression in dorsal CA1 was observed following retrieval in the original context, but not in a novel context, whether or not the memory was reactivated, suggesting that dCA1 retains the context-specific representation. c-Fos was highly expressed in aCC following remote memory testing in both contexts, regardless of reminder condition, indicating that aCC develops generalized representations that are insensitive to memory reactivation.

Schemas are foundational mental structures shaped by experience. They influence behaviour, guide the encoding of new memories and are shaped by associated information. The adaptability of memory schemas facilitates the integration of new information that aligns with existing knowledge structures. First, we discuss how novel information consistent with an existing schema can be swiftly assimilated when presented. This cognitive updating is facilitated by the interaction between the hippocampus and the prefrontal cortex. Second, when novel information is inconsistent with the schema, it likely engages the hippocampus to encode the information as part of an episodic memory trace. Third, novelty may enhance hippocampal dopamine through either the locus coeruleus or ventral tegmental area pathways, with the pathway involved potentially depending on the type of novelty encountered. We propose a gradient theory of schema and novelty to elucidate the neural processes by which schema updating or novel memory traces are formed. It is likely that experiences vary along a familiarity–novelty continuum, and the degree to which new experiences are increasingly novel will guide whether memory for a new experience either integrates into an existing schema or prompts the creation of a new cognitive framework. This article is part of the theme issue 'Long-term potentiation: 50 years on'. [ABSTRACT FROM AUTHOR]

Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired, while memory for central details is relatively spared. Given the sensitivity of memory to loss of details, the present study sought to investigate factors that mediate the forgetting of different types of information from naturalistic episodic memories in young healthy adults. The study investigated (1) time-dependent loss of "central" and "peripheral" details from episodic memories, (2) the effectiveness of cuing with reminders to reinstate memory details, and (3) the role of retrieval in preventing forgetting. Over the course of 7 d, memory for naturalistic events (film clips) underwent a time-dependent loss of peripheral details, while memory for central details (the core or gist of events) showed significantly less loss. Giving brief reminders of the clips just before retrieval reinstated memory for peripheral details, suggesting that loss of details is not always permanent, and may reflect both a storage and retrieval deficit. Furthermore, retrieving a memory shortly after it was encoded prevented loss of both central and peripheral details, thereby promoting retention over time. We consider the implications of these results for behavioral and neurobiological models of retention and forgetting.

Although the transcription factor CREB has been widely implicated in memory, whether it is sufficient to produce spatial memory under conditions that do not normally support memory formation in mammals is unknown. We found that locally and acutely increasing CREB levels in the dorsal hippocampus using viral vectors is sufficient to induce robust spatial memory in two conditions that do not normally support spatial memory, weakly trained wild-type (WT) mice and strongly trained mutant mice with a brain-wide disruption of CREB function. Together with previous results, these findings indicate that CREB is both necessary and sufficient for spatial memory formation, and highlight its pivotal role in the hippocampal molecular machinery underlying the formation of spatial memory.

Replicas of an aspect of an experienced event can serve as effective reminders, yet little is known about the neural basis of such reminding effects. Here we examined the neural activity underlying the memory‐enhancing effect of reminders 1 week after encoding of naturalistic film clip events. We used fMRI to determine differences in network activity associated with recently reactivated memories relative to comparably aged, non‐reactivated memories. Reminders were effective in facilitating overall retrieval of memory for film clips, in an all‐or‐none fashion. Prefrontal cortex and hippocampus were activated during both reminders and retrieval. Peak activation in ventro‐lateral prefrontal cortex (vPFC) preceded peak activation in the right hippocampus during the reminders. For film clips that were successfully retrieved after 7 days, pre‐retrieval reminders did not enhance the quality of the retrieved memory or the number of details retrieved, nor did they more strongly engage regions of the recollection network than did successful retrieval of a non‐reminded film clip. These results suggest that reminders prior to retrieval are an effective means of boosting retrieval of otherwise inaccessible episodic events, and that the inability to recall certain events after a delay of a week largely reflects a retrieval deficit, rather than a storage deficit for this information. The results extend other evidence that vPFC drives activation of the hippocampus to facilitate memory retrieval and scene construction, and show that this facilitation also occurs when reminder cues precede successful retrieval attempts. The time course of vPFC‐hippocampal activity during the reminder suggests that reminders may first engage schematic information meditated by vPFC followed by a recollection process mediated by the hippocampus. [ABSTRACT FROM AUTHOR]

Medulloblastomas, the most common malignant brain tumor in children, are typically treated with radiotherapy. Refinement of this treatment has greatly improved survival rates in this patient population. However, radiotherapy also profoundly affects the developing brain and is associated with reduced hippocampal volume and blunted hippocampal neurogenesis. Such hippocampal (as well as extrahippocampal) abnormalities likely contribute to cognitive impairments in this population. While several aspects of memory have been examined in this population, the impact of radiotherapy on autobiographical memory has not previously been evaluated. Here we evaluated autobiographical memory in male and female patients who received radiotherapy for posterior fossa tumors (PFTs), including medulloblastoma, during childhood. Using the Children's Autobiographical Interview, we retrospectively assessed episodic and nonepisodic details for events that either preceded (i.e., remote) or followed (i.e., recent) treatment. For post-treatment events, PFT patients reported fewer episodic details compared with control subjects. For pretreatment events, PFT patients reported equivalent episodic details compared with control subjects. In a range of conditions associated with reduced hippocampal volume (including medial temporal lobe amnesia, mild cognitive impairment, Alzheimer's disease, temporal lobe epilepsy, transient epileptic amnesia, frontal temporal dementia, traumatic brain injury, encephalitis, and aging), loss of episodic details (even in remote memories) accompanies hippocampal volume loss. It is therefore surprising that pretreatment episodic memories in PFT patients with reduced hippocampal volume are retained. We discuss these findings in light of the anterograde and retrograde impact on memory of experimentally suppressing hippocampal neurogenesis in rodents. [ABSTRACT FROM AUTHOR]

Memory stabilization following encoding (synaptic consolidation) or memory reactivation (reconsolidation) requires gene expression and protein synthesis (Dudai and Eisenberg, 2004; Tronson and Taylor, 2007; Nader and Einarsson, 2010; Alberini, 2011). Although consolidation and reconsolidation may be mediated by distinct molecular mechanisms (Lee et al., 2004), disrupting the function of the transcription factor CREB impairs both processes (Kida et al., 2002; Mamiya et al., 2009). Phosphorylation of CREB at Ser 133 recruits CREB binding protein (CBP)/p300 coactivators to activate transcription (Chrivia et al., 1993; Parker et al., 1996). In addition to this well known mechanism, CREB regulated transcription coactivators (CRTCs), previously called transducers of regulated CREB (TORC) activity, stimulate CREB-mediated transcription, even in the absence of CREB phosphorylation. Recently, CRTC1 has been shown to undergo activity-dependent trafficking from synapses and dendrites to the nucleus in excitatory hippocampal neurons (Ch'ng et al., 2012). Despite being a powerful and specific coactivator of CREB, the role of CRTC in memory is virtually unexplored. To examine the effects of increasing CRTC levels, we used viral vectors to locally and acutely increase CRTC1 in the dorsal hippocampus dentate gyrus region of mice before training or memory reactivation in context fear conditioning. Overexpressing CRTC1 enhanced both memory consolidation and reconsolidation; CRTC 1-mediated memory facilitation was context specific (did not generalize to nontrained context) and long lasting (observed after virally expressed CRTC 1 dissipated). CREB overexpression produced strikingly similar effects. Therefore, increasing CRTC1 or CREB function is sufficient to enhance the strength of new, as well as established reactivated, memories without compro-mising memory quality. [ABSTRACT FROM AUTHOR]