Encoding Of Novel Information Research Articles

Visual sequence encoding is modulated by music schematic structure and familiarity.

Music is omnipresent in daily life and may interact with critical cognitive processes including memory. Despite music's presence during diverse daily activities including studying, commuting, or working, existing literature has yielded mixed results as to whether music improves or impairs memory for information experienced in parallel. To elucidate how music memory and its predictive structure modulate the encoding of novel information, we developed a cross-modal sequence learning task during which participants acquired sequences of abstract shapes accompanied with paired music. Our goal was to investigate whether familiar and structurally regular music could provide a "temporal schema" (rooted in the organized and hierarchical structure of music) to enhance the acquisition of parallel temporally-ordered visual information. Results revealed a complex interplay between music familiarity and music structural regularity in learning paired visual sequences. Notably, compared to a control condition, listening to well-learned, regularly-structured music (music with high predictability) significantly facilitated visual sequence encoding, yielding quicker learning and retrieval speed. Conversely, learned but irregular music (where music memory violated musical syntax) significantly impaired sequence encoding. While those findings supported our mechanistic framework, intriguingly, unlearned irregular music-characterized by the lowest predictability-also demonstrated memory enhancement. In conclusion, this study demonstrates that concurrent music can modulate visual sequence learning, and the effect varies depending on the interaction between both music familiarity and regularity, offering insights into potential applications for enhancing human memory.

59 Preliminary Findings of Semantic Interference in Learning and Memory Processes in Manifest Huntington’s Disease

Objective:To explore the usefulness of the Lowenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) [Crocco et al, 2013], a novel memory-based cognitive stress test capitalizing on semantic interference, in Huntington’s Disease (HD).Participants and Methods:12 healthy adults (HA) and 14 individuals with manifest HD were administered the LASSI-L as part of an annual research visit with the UCSD Huntington’s Disease Clinical Research Center (HDCRC.) Participants in each group were well matched with regard to age and education. Individuals with manifest HD had an average MoCA score of 26, total functional capacity score of 10, and total motor score of 21 suggesting that they were in the early stages of HD. The LASSI-L examines different types of semantic interference that occur in the learning/encoding process. There are free and cued recall trials for two lists of semantically related words with certain trials specific to different aspects of semantic interference including proactive, retroactive, and failure to recover from proactive interference. T-tests for all recall trials and number of intrusions for each trial were conducted between HA and those with HD to examine whether HD renders one more prone to semantic interference in both encoding and retrieval memory processes.Results:Individuals with HD recalled fewer words on average than HA across all recall trials except for the initial free recall of the first word list. HD individuals recalled significantly fewer (∼1.5) words during the initial (t=-2.8, p=.005, Cohen’s d=2.7) and secondary (t=-2.9, p=.003, Cohen’s d=2.6) cued recall trials from the words on the first list. Individuals with HD also recalled significantly fewer words on initial free recall (t=-2.9, p=.003, Cohen’s d=2.6) and cued recall trials of the second list, with the initial cued recall (t=-2.8, p=.005, Cohen’s d=3.1) sensitive to proactive semantic interference and the second cued recall (t=-3.3, p=.001, Cohen’s d=2.6) sensitive to failure to recover from proactive semantic interference. In addition, individuals with HD also recalled significantly fewer (∼2.2) words on delayed cued recall of the first list, a measure of retroactive semantic interference, than HA (t=-4.8, p<.001, Cohen’s d=2.4). Lastly, individuals with HD recalled fewer (∼4.1) words than HA on delayed free recall of both word lists (t=-3.5, p<.001, Cohen’s d=5.9). The groups did not differ significantly with regard to number of total intrusions per trial.Conclusions:Overall, our study supports the usefulness of the LASSI-L for neuropsychological assessment of HD in clinical and research settings. In comparison to a demographically similar group of HA, individuals with manifest HD showed significant differences in frontally mediated retrieval processes as well as semantic interference processes that affect efficient encoding of novel information.

Prompting teaching modulates children's encoding of novel information by facilitating higher-level structure learning and hindering lower-level statistical learning

Young children are not only prepared to learn from teaching, but they also start to spontaneously teach others, indicating that teaching is a natural instinct of the humankind. During childhood, teaching seems to precede the emergence of several cognitive abilities, so the question arises: how does teaching affect the development of later emerging cognitive skills? Since teaching requires explicit, accessible representations of the knowledge of the teacher, we hypothesized that the motivation to teach might impact the way children encode novel information, by biasing them towards a model-based encoding, which can help them to structure the incoming information in a more abstract and explicitly accessible way. In our study, 7–10-year-old children were presented with a well-established probabilistic sequence learning task on two consecutive days, after receiving an instruction that on the second day, they would have to teach a peer about the task. During the task, we could simultaneously measure two different types of learning: model-free learning of local (lower-level) statistical correlations and model-based learning of the global (higher-level) statistical structures of the sequences. We predicted that in case the motivation to teach facilitates model-based encoding, children who received the instruction to teach would perform better in learning the higher-level statistical structures than children in the control group, who did not receive an instruction to teach. Furthermore, since previous studies showed competition between the two types of encoding processes during development, we also predicted that facilitating children's model-based learning will impair their model-free learning of the lower-level statistical correlations. Our results confirmed both predictions, showing an improved model-based higher-level structure learning and an impaired model-free lower-level statistical correlation learning in the Teaching Group, compared to the controls. Thus, prompting teaching affects children's encoding of the novel information, by biasing them to learn in a model-based way, which can help to build more abstract and explicitly accessible representations that could be shared with others.

Questions Can Answer Questions About Mechanisms of Preschoolers' Selective Word Learning.

This study examined how inferences about epistemic competence and generalized labeling errors influence children's selective word learning. Three- to 4-year-olds (N=128) learned words from informants who asked questions about objects, mentioning either correct or incorrect labels. Such questions do not convey stark differences in informants' epistemic competence. Inaccurate labels, however, generate error signals that can lead to weaker encoding of novel information. Preschoolers retained novel labels from both informants but were slower to respond in the Inaccurate Labeler condition. When the test procedure was not sensitive to the strength of information encoding, children performed above chance in both conditions and their response times did not differ. These results suggest that epistemic-level inferences and error generalizations influence preschoolers' selective word learning concurrently.

Mnemonic prediction errors bias hippocampal states

When our experience violates our predictions, it is adaptive to upregulate encoding of novel information, while down-weighting retrieval of erroneous memory predictions to promote an updated representation of the world. We asked whether mnemonic prediction errors promote hippocampal encoding versus retrieval states, as marked by distinct network connectivity between hippocampal subfields. During fMRI scanning, participants were cued to internally retrieve well-learned complex room-images and were then presented with either an identical or a modified image (0-4 changes). In the left hemisphere, we find that CA1-entorhinal connectivity increases, and CA1-CA3 connectivity decreases, with the number of changes. Further, in the left CA1, the similarity between activity patterns during cued-retrieval of the learned room and during the image is lower when the image includes changes, consistent with a prediction error signal in CA1. Our findings provide a mechanism by which mnemonic prediction errors may drive memory updating—by biasing hippocampal states.

Hippocampal theta coordinates memory processing during visual exploration.

The hippocampus supports memory encoding and retrieval, which may occur at distinct phases of the theta cycle. These processes dynamically interact over rapid timescales, especially when sensory information conflicts with memory. The ability to link hippocampal dynamics to memory-guided behaviors has been limited by experiments that lack the temporal resolution to segregate encoding and retrieval. Here, we simultaneously tracked eye movements and hippocampal field potentials while neurosurgical patients performed a spatial memory task. Phase-locking at the peak of theta preceded fixations to retrieved locations, indicating that the hippocampus coordinates memory-guided eye movements. In contrast, phase-locking at the trough of theta followed fixations to novel object-locations and predicted intact memory of the original location. Theta-gamma phase amplitude coupling increased during fixations to conflicting visual content, but predicted memory updating. Hippocampal theta thus supports learning through two interleaved processes: strengthening encoding of novel information and guiding exploration based on prior experience.

Learning from failure: Errorful generation improves memory for items, not associations

Abstract Potts and Shanks (2014) recently reported that making mistakes improved the encoding of novel information compared with simply studying. This benefit of generating errors is counterintuitive, since it resulted in less study time and more opportunity for proactive interference. Five experiments examined the effect of generating errors versus studying on item recognition, cued recall, associative recognition, two-alternative forced choice and multiple-choice performance. Following Potts and Shanks (2014), participants first attempted to learn the English definitions of either very rare English words or Euskara nouns. During encoding, participants either guessed the definition (and almost always made an error) before the correct definition was revealed, or simply studied the words for an equivalent period. Experiments 1–4 used rare English words. In these experiments, generating errors led to better subsequent recognition of both the cues and targets compared with studying (Experiments 1 and 3). Tests of cued recall and associative recognition, by contrast, revealed no significant benefit of generating errors over studying (Experiments 1–3). Generating errors during encoding also improved performance on a two-alternative forced choice test when the correct target was presented with a novel foil, but not when the familiarity of the target and the foil was matched (Experiment 4). In Experiment 5, a different set of materials – Euskara nouns – and a different (intermixed) encoding procedure was adopted. Here, guessing improved target recognition (performance was improved on a multiple-choice test with unfamiliar foils), but impaired cued recall performance. These results suggest that, when learning word pairs that do not have a pre-existing semantic association, generating errors strengthens the cues and targets in isolation, but does not strengthen the cue-target associations.

Effects of M1 and M4 activation on excitatory synaptic transmission in CA1.

Hippocampal networks are particularly susceptible to dysfunction in many neurodegenerative diseases and neuropsychiatric disorders including Alzheimer's disease, Lewy body dementia, and schizophrenia. CA1, a major output region of the hippocampus, receives glutamatergic input from both hippocampal CA3 and entorhinal cortex, via the Schaffer collateral (SC) and temporoammonic (TA) pathways, respectively. SC and TA inputs to CA1 are thought to be differentially involved in the retrieval of previously stored memories versus the encoding of novel information, and switching between these two crucial hippocampal functions is thought to critically depend on acetylcholine (ACh) acting at muscarinic receptors. In this study, we aimed to determine the roles of specific subtypes of muscarinic receptors in mediating the neuromodulatory effects of ACh on glutamatergic synaptic transmission in the SC and TA pathways of CA1. Using selective pharmacological activation of M1 or M4 receptors along with extracellular and intracellular electrophysiology recordings from adult rat hippocampal slices, we demonstrate that activation of M1 receptors increases spontaneous spike rates of neuronal ensembles in CA1 and increases the intrinsic excitability of pyramidal neurons and interneurons. Selective activation of M4 receptors inhibits glutamate release in the SC pathway, while leaving synaptic transmission in the TA pathway comparatively intact. These results suggest specific mechanisms by which M1 and M4 activation may normalize CA1 circuit activity following disruptions of signaling that accompany neurodegenerative dementias or neuropsychiatric disorders. These findings are of particular interest in light of clinical findings that xanomeline, an M1/M4 preferring agonist, was able to improve cognitive and behavioral symptoms in patients with Alzheimer's disease or schizophrenia.

Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding

Adult-born granule cells (abGCs) have been implicated in cognition and mood; however, it remains unknown how these cells behave invivo. Here, we have used two-photon calcium imaging to monitor the activity of young abGCs in awake behaving mice. We find that young adult-born neurons fire at a higher rate invivo but paradoxically exhibit less spatial tuning than their mature counterparts. When presented with different contexts, mature granule cells underwent robust remapping of their spatial representations, and the few spatially tuned adult-born cells remapped to a similar degree. We next used optogenetic silencing to confirm the direct involvement of abGCs in context encoding and discrimination, consistent with their proposed role in pattern separation. These results provide the first invivo characterization of abGCs and reveal their participation in the encoding of novel information.

Fronto-limbic novelty processing in acute psychosis: disrupted relationship with memory performance and potential implications for delusions.

Recent concepts have highlighted the role of the hippocampus and adjacent medial temporal lobe (MTL) in positive symptoms like delusions in schizophrenia. In healthy individuals, the MTL is critically involved in the detection and encoding of novel information. Here, we aimed to investigate whether dysfunctional novelty processing by the MTL might constitute a potential neural mechanism contributing to the pathophysiology of delusions, using functional magnetic resonance imaging (fMRI) in 16 unmedicated patients with paranoid schizophrenia and 20 age-matched healthy controls. All patients experienced positive symptoms at time of participation. Participants performed a visual target detection task with complex scene stimuli in which novel and familiar rare stimuli were presented randomly intermixed with a standard and a target picture. Presentation of novel relative to familiar images was associated with hippocampal activation in both patients and healthy controls, but only healthy controls showed a positive relationship between novelty-related hippocampal activation and recognition memory performance after 24 h. Patients, but not controls, showed a robust neural response in the orbitofrontal cortex (OFC) during presentation of novel stimuli. Functional connectivity analysis in the patients further revealed a novelty-related increase of functional connectivity of both the hippocampus and the OFC with the rostral anterior cingulate cortex (rACC) and the ventral striatum (VS). Notably, delusions correlated positively with the difference of the functional connectivity of the hippocampus vs. the OFC with the rACC. Taken together, our results suggest that alterations of fronto-limbic novelty processing may contribute to the pathophysiology of delusions in patients with acute psychosis.

Doublecortin Knockout Mice Show Normal Hippocampal-Dependent Memory Despite CA3 Lamination Defects

Mutations in the human X-linked doublecortin gene (DCX) cause major neocortical disorganization associated with severe intellectual disability and intractable epilepsy. Although Dcx knockout (KO) mice exhibit normal isocortical development and architecture, they show lamination defects of the hippocampal pyramidal cell layer largely restricted to the CA3 region. Dcx-KO mice also exhibit interneuron abnormalities. As well as the interest of testing their general neurocognitive profile, Dcx-KO mice also provide a relatively unique model to assess the effects of a disorganized CA3 region on learning and memory. Based on its prominent anatomical and physiological features, the CA3 region is believed to contribute to rapid encoding of novel information, formation and storage of arbitrary associations, novelty detection, and short-term memory. We report here that Dcx-KO adult males exhibit remarkably preserved hippocampal- and CA3-dependant cognitive processes using a large battery of classical hippocampus related tests such as the Barnes maze, contextual fear conditioning, paired associate learning and object recognition. In addition, we show that hippocampal adult neurogenesis, in terms of proliferation, survival and differentiation of granule cells, is also remarkably preserved in Dcx-KO mice. In contrast, following social deprivation, Dcx-KO mice exhibit impaired social interaction and reduced aggressive behaviors. In addition, Dcx-KO mice show reduced behavioral lateralization. The Dcx-KO model thus reinforces the association of neuropsychiatric behavioral impairments with mouse models of intellectual disability.

Reduced Threshold for Induction of LTP by Activation of Dopamine D1/D5 Receptors at Hippocampal CA1–Subiculum Synapses

The phasic release of dopamine in the hippocampal formation has been shown to facilitate the encoding of novel information. There is evidence that the subiculum operates as a detector and distributor of sensory information, which incorporates the novelty and relevance of signals received from CA1. The subiculum acts as the final hippocampal relay station for outgoing information. Subicular pyramidal cells have been classified as regular- and burst-spiking neurons. The goal of the present study was to study the effect of dopamine D1/D5 receptor activation on synaptic transmission and plasticity in the subicular regular-spiking neurons of 4–6 week old Wistar rats. We demonstrate that prior activation of D1/D5 receptors reduces the threshold for the induction of long-term potentiation (LTP) in subicular regular-spiking neurons. Our results indicate that D1/D5 receptor activation facilitates a postsynaptic form of LTP in subicular regular-spiking cells that is NMDA receptor-dependent, relies on postsynaptic Ca2+ signaling, and requires the activation of protein kinase A. The enhanced propensity of subicular regular-spiking cells to express postsynaptic LTP after activation of D1/D5 receptors provides an intriguing mechanism for the encoding of hippocampal output information.

Genetic Variation of the Serotonin 2a Receptor Affects Hippocampal Novelty Processing in Humans

Serotonin (5-hydroxytryptamine, 5-HT) is an important neuromodulator in learning and memory processes. A functional genetic polymorphism of the 5-HT 2a receptor (5-HTR2a His452Tyr), which leads to blunted intracellular signaling, has previously been associated with explicit memory performance in several independent cohorts, but the underlying neural mechanisms are thus far unclear. The human hippocampus plays a critical role in memory, particularly in the detection and encoding of novel information. Here we investigated the relationship of 5-HTR2a His452Tyr and hippocampal novelty processing in 41 young, healthy subjects using functional magnetic resonance imaging (fMRI). Participants performed a novelty/familiarity task with complex scene stimuli, which was followed by a delayed recognition memory test 24 hours later. Compared to His homozygotes, Tyr carriers exhibited a diminished hippocampal response to novel stimuli and a higher tendency to judge novel stimuli as familiar during delayed recognition. Across the cohort, the false alarm rate during delayed recognition correlated negatively with the hippocampal novelty response. Our results suggest that previously reported effects of 5-HTR2a on explicit memory performance may, at least in part, be mediated by alterations of hippocampal novelty processing.

Activation of dopamine D1/D5 receptors facilitates the induction of presynaptic long‐term potentiation at hippocampal output synapses

Encoding of novel information has been proposed to rely on the time-locked release of dopamine in the hippocampal formation during novelty detection. However, the site of novelty detection in the hippocampus remains a matter of debate. According to current models, the CA1 and the subiculum act as detectors and distributors of novel sensory information. Although most CA1 pyramidal neurons exhibit regular-spiking behavior, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials. The present study investigates the efficacy of dopamine D1/D5 receptor activation to facilitate the induction of activity-dependent long-term potentiation (LTP) in rat CA1 regular-spiking and subicular burst-spiking pyramidal cells. Using a weak stimulation protocol, set at a level subthreshold for the induction of LTP, we show that activation of D1/D5 receptors for 5-10 min facilitates LTP in subicular burst-spiking neurons but not in CA1 neurons. The results demonstrate that D1/D5 receptor-facilitated LTP is NMDA receptor-dependent, and requires the activation of protein kinase A. In addition, the D1/D5 receptor-facilitated LTP is shown to be presynaptically expressed and relies on presynaptic Ca(2+) signaling. The phenomenon of dopamine-induced facilitation of presynaptic NMDA receptor-dependent LTP in subicular burst-spiking pyramidal cells is in accordance with observations of the time-locked release of dopamine during novelty detection in this brain region, and reveals an intriguing mechanism for the encoding of hippocampal output information.

Sleep-dependent directional coupling between human neocortex and hippocampus

Complex interactions between neocortex and hippocampus are the neural basis of memory formation. Two-step theories of memory formation suggest that initial encoding of novel information depends on the induction of rapid plasticity within the hippocampus, and is followed by a second sleep-dependent step of memory consolidation. These theories predict information flow from the neocortex into the hippocampus during waking state and in the reverse direction during sleep. However, experimental evidence that interactions between hippocampus and neocortex have a predominant direction which reverses during sleep rely on cross-correlation analysis of data from animal experiments and yielded inconsistent results. Here, we investigated directional coupling in intracranial EEG data from human subjects using a phase-modeling approach which is well suited to reveal functional interdependencies in oscillatory data. In general, we observed that the anterior hippocampus predominantly drives nearby and remote brain regions. Surprisingly, however, the influence of neocortical regions on the hippocampus significantly increased during sleep as compared to waking state. These results question the standard model of hippocampal–neocortical interactions and suggest that sleep-dependent consolidation is accomplished by an active retrieval of hippocampal information by the neocortex.

Encoding touch and the orbitofrontal cortex

Lesion studies on nonhuman primates utilizing recognition memory tests have shown that the orbitofrontal cortex is critical for the encoding of novel information, and anatomical studies have shown that the orbitofrontal cortex forms part of a mnemonic circuit that connects limbic medial temporal areas with higher-order lateral frontal cortical regions. Furthermore, functional neuroimaging studies have demonstrated increased activity in the orbitofrontal cortex of the human brain during the encoding of novel visual and auditory information. The present positron emission tomography study examined brain activity related to the encoding of tactile information. Cerebral blood flow (CBF) in normal human subjects during the tactile exploration of novel stimuli from a related set of textures and patterns, as well as from a set of aversive tactile stimuli, was compared with CBF during a control condition involving familiar tactile stimuli. The results demonstrate that the right rostral orbitofrontal cortex is involved in the active encoding of novel tactile information, while a more caudal region of the orbitofrontal cortex, which is more closely connected with limbic and autonomic regions of the brain, was activated when subjects explored novel aversive tactile stimuli. These results suggest that the orbitofrontal cortex, through its connections with the limbic areas of the medial temporal lobe, influences the processing of incoming information and thus contributes to its encoding.

FMRI Activation Changes during Successful Episodic Memory Encoding and Recognition in Amnestic Mild Cognitive Impairment Relative to Cognitively Healthy Older Adults

Background/Aims: Previous functional MRI studies in individuals with amnestic mild cognitive impairment (AMCI), a putative, prodromal form of Alzheimer’s disease, reveal substantial regional changes in brain activation during episodic memory function. Methods: Functional MRI was applied to examine changes in brain activation during different stages of episodic memory function using a subsequent memory task in individuals with AMCI relative to older normal controls. Results: We found that the AMCI group displayed greater activation in the right hippocampus but less activation in the frontal cortex relative to the older normal control group during intentional encoding of items that were subsequently recognized. We observed nearly the opposite pattern of results for successful recognition. The AMCI group displayed less activation in the medial temporal cortex but greater activation in the frontal cortex. In addition, the AMCI group showed reduced activation in the medial temporal and frontal cortices during incidental encoding of novel information during recognition. Conclusion: The results of the present study suggest that brain activation differences in individuals with AMCI are modulated by the stage of episodic memory examined (i.e. intentional vs. incidental encoding vs. recognition). These observations may help to clarify some of the conflicting findings regarding brain activation changes in AMCI.

Modulation of CA3 Afferent Inputs by Novelty and Theta Rhythm

Models of hippocampal function suggest that the modulation of CA3 afferent input during theta rhythm allows for a rapid alternation between encoding and retrieval states, with each phase enhancing either extrinsic or intrinsic CA3 afferents, favoring either encoding or retrieval, respectively. Here, we show that during the initial exploration of a novel environment by rats, intrinsic CA3-CA3 synaptic inputs are attenuated on CA3 theta peaks, favoring extrinsic CA3 inputs, whereas extrinsic perforant path-CA3 synaptic inputs are attenuated on CA3 theta troughs, favoring intrinsic CA3 inputs. This modulation is absent when animals are re-exposed to the same environment 2 or 48 h later and thus habituates with familiarity, suggesting a process involved in learning. Modulation of CA3 synaptic inputs during novelty was blocked by atropine at a dose that blocks type 2 theta rhythm. Re-exposure to the same novel environment 48 h later in the absence of atropine did not result in habituation, but instead modulated CA3 synaptic responses as though the environment were novel and explored for the first time. The NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), administered in a dose that blocks long-term potentiation induction, did not alter CA3 synaptic modulation during initial exploration. However, like atropine, CPP blocked the habituation of synaptic modulation normally observed with re-exposure, as though the environment were novel and explored for the first time. Thus, as predicted theoretically, recurrent and cortical CA3 afferents are differentially modulated during phases of theta rhythm. This modulation is atropine sensitive and habituates in an NMDA receptor-dependent manner, suggesting an NMDA receptor-dependent process that, in conjunction with theta rhythm, contributes to encoding of novel information in the hippocampus.

Distinct Patterns of Neural Activity during Memory Formation of Nonwords versus Words

Research into the neural underpinnings of memory formation has focused on the encoding of familiar verbal information. Here, we address how the brain supports the encoding of novel information that does not have meaning. Electrical brain activity was recorded from the scalps of healthy young adults while they performed an incidental encoding task (syllable judgments) on separate series of words and "nonwords" (nonsense letter strings that are orthographically legal and pronounceable). Memory for the items was then probed with a recognition memory test. For words as well as nonwords, event-related potentials differed depending on whether an item would subsequently be remembered or forgotten. However, the polarity and timing of the effect varied across item type. For words, subsequently remembered items showed the usually observed positive-going, frontally distributed modulation from around 600 msec after word onset. For nonwords, by contrast, a negative-going, spatially widespread modulation predicted encoding success from 1000 msec onward. Nonwords also showed a modulation shortly after item onset. These findings imply that the brain supports the encoding of familiar and unfamiliar letter strings in qualitatively different ways, including the engagement of distinct neural activity at different points in time. The processing of semantic attributes plays an important role in the encoding of words and the associated positive frontal modulation.

Enigmas of the Dentate Gyrus

We are rapidly approaching a better understanding of the mechanisms that allow our brains to form distinct representations for similar events or episodes. McHugh et al. have brought that goal one step closer by showing that NMDA receptor-dependent synaptic plasticity in the dentate gyrus is necessary for immediate differentiation between environments with similar features.