Scopolamine infused into perirhinal cortex improves object recognition memory by blocking the acquisition of interfering object information

In a previous study, we reported apparently paradoxical facilitation of object recognition memory following infusions of the cholinergic muscarinic receptor antagonist scopolamine into the perirhinal cortex (PRh) of rats. We attributed these effects to the blockade by scopolamine of the acquisition of interfering information. The present study tested this possibility directly by modifying the spontaneous object recognition memory task to allow the presentation of a potentially interfering object either before the sample phase or in the retention delay between the sample and choice phases. Presentation of an object between the sample and choice phases disrupted subsequent recognition of the sample object (retroactive interference), and intra-PRh infusions of scopolamine prior to the presentation of the irrelevant object prevented this retroactive interference effect. Moreover, presentation of an irrelevant object prior to the sample phase interfered proactively with sample object recognition, and intra-PRh infusions of scopolamine prior to the presentation of the pre-sample object prevented this proactive interference effect. These results suggest that blocking muscarinic cholinergic receptors in PRh can disrupt the acquisition of potentially interfering object information, thereby facilitating object recognition memory. This finding provides further, strong evidence that acetylcholine is important for the acquisition of object information in PRh.     

Muscimol,AP5, or scopolamine infused into perirhinal cortex impairs two-choice visual discrimination learning in rats

The perirhinal cortex (PRh) has been strongly implicated in object recognition memory and visual stimulus representation. Studies of object recognition have revealed evidence for the involvement of several neurotransmitter subsystems, including those involving NMDA (N-methyl-d-aspartic acid) and muscarinic cholinergic receptors. In the present study, we assessed the possible involvement of PRh and related receptor subsystems in two-choice visual discrimination learning by Lister Hooded rats tested in touchscreen-equipped operant boxes. In Experiment 1, daily pre-training inactivation of PRh with the GABA_A receptor agonist muscimol (0.5 μg/hemisphere) significantly impaired acquisition of the two-choice visual discrimination. In Experiment 2, daily pre-training blockade of either NMDA or muscarinic receptors in PRh with AP5 (5.9 μg/hemisphere) or scopolamine (10 μg/hemisphere), respectively, impaired task acquisition. These results parallel the findings from object recognition studies and suggest a generality of neurotransmitter receptor involvement underlying the role of PRh in both object recognition memory and visual discrimination learning. The involvement of PRh in both types of tasks may be related to its role in complex visual stimulus representation.     

Perirhinal cortex resolves feature ambiguity in configural object recognition and perceptual oddity tasks

The perirhinal cortex (PRh) has a well-established role in object recognition memory. More recent studies suggest that PRh is also important for two-choice visual discrimination tasks. Specifically, it has been suggested that PRh contains conjunctive representations that help resolve feature ambiguity, which occurs when a task cannot easily be solved on the basis of features alone. However, no study has examined whether the ability of PRh to resolve configural feature ambiguity is related to its role in object recognition. Therefore, we examined whether bilateral excitotoxic lesions of PRh or PPRh (perirhinal plus post-rhinal cortices) in the rat would cause deficits in a configural spontaneous object recognition task, and a configural simultaneous oddity discrimination task, in which the task could not be solved on the basis of features, but could only be solved using conjunctive representations. As predicted by simulations using a computational model, rats with PPRh lesions were impaired during a minimal-delay configural object recognition task. These same rats were impaired during a zero-delay configural object recognition task. Furthermore, rats with localized PRh lesions were impaired in a configural simultaneous oddity discrimination task. These findings support the idea that PRh contains conjunctive representations for the resolution of feature ambiguity and that these representations underlie a dual role for PRh in memory and perception.     

Contributions of area Te2 to rat recognition memory

Ablations and local intracerebral infusions were used to determine the role of rat temporal association cortex (area Te2) in object recognition memory, so that this role might be compared with that of the adjacent perirhinal cortex (PRH). Bilateral lesions of Te2 impaired recognition memory measured by preferential exploration of a novel rather than a familiar object at delays ≥20 min but not after a 5-min delay. Local infusion bilaterally into Te2 of (1) CNQX to block AMPA/kainate receptors or (2) lidocaine to block axonal transmission or (3) AP5, an NMDA receptor antagonist, impaired recognition memory after a 24-h but not a 20-min delay. In PRH all these manipulations impair recognition memory after a 20-min as well as a 24-h delay. UBP302, a GluK1 kainate receptor antagonist, impaired recognition memory after a 24-h but not a 20-min delay, contrasting with its action in PRH where it impairs only shorter-term (20 min) recognition memory. Also in contrast to PRH, infusion of the muscarinic receptor antagonist scopolamine was without effect. The Te2 impairments could not readily be ascribed to perceptual deficits. Hence, Te2 is essential for object recognition memory at delays >5 or 20 min. Thus, at long delays both area Te2 and PRH are necessary for object recognition memory.     

The consolidation of object and context recognition memory involve different regions of the temporal lobe

These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory training. Anisomycin infused into perirhinal or insular cortices blocked long-term (24 h), but not short-term (90 min) object recognition memory. Infusions into the hippocampus or amygdala did not impair object recognition memory. Anisomycin infused into the hippocampus blocked long-term, but not short-term object-in-context recognition memory, whereas infusions administered into the perirhinal cortex, insular cortex, or amygdala did not affect object-in-context recognition memory. These results clearly indicate that distinct regions of the temporal lobe are differentially involved in long-term object and object-in-context recognition memory. Whereas perirhinal and insular cortices are required for consolidation of familiar objects, the hippocampus is necessary for consolidation of contextual information of recognition memory. Altogether, these results suggest that temporal lobe structures are differentially involved in recognition memory consolidation.     

Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory

Deletion of the GluA1 AMPA receptor subunit impairs short-term spatial recognition memory. It has been suggested that short-term recognition depends upon memory caused by the recent presentation of a stimulus that is independent of contextual-retrieval processes. The aim of the present set of experiments was to test whether the role of GluA1 extends to nonspatial recognition memory. Wild-type and GluA1 knockout mice were tested on the standard object recognition task and a context-independent recognition task that required recency-dependent memory. In a first set of experiments it was found that GluA1 deletion failed to impair performance on either of the object recognition or recency-dependent tasks. However, GluA1 knockout mice displayed increased levels of exploration of the objects in both the sample and test phases compared to controls. In contrast, when the time that GluA1 knockout mice spent exploring the objects was yoked to control mice during the sample phase, it was found that GluA1 deletion now impaired performance on both the object recognition and the recency-dependent tasks. GluA1 deletion failed to impair performance on a context-dependent recognition task regardless of whether object exposure in knockout mice was yoked to controls or not. These results demonstrate that GluA1 is necessary for nonspatial as well as spatial recognition memory and plays an important role in recency-dependent memory processes.     

Hippocampal CA1 spiking during encoding and retrieval: relation to theta phase

The hippocampal theta rhythm is a prominent oscillation in the field potential observed throughout the hippocampus as a rat investigates stimuli in the environment. A recent computational model [Hasselmo, M. E., Bodelon, C., & Wyble, B. P. (2002a). A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning. Neural Computation, 14, 793-817. Neuromodulation, theta rhythm and rat spatial navigation. Neural Networks, 15, 689-707] suggested that the theta rhythm allows the hippocampal formation to alternate rapidly between conditions that promote memory encoding (strong synaptic input from entorhinal cortex to areas CA3 and CA1) and conditions that promote memory retrieval (strong synaptic input from CA3 to CA1). That model predicted that the preferred theta phase of CA1 spiking should differ for information being encoded versus information being retrieved. In the present study, the spiking activity of CA1 pyramidal cells was recorded while rats performed either an odor-cued delayed nonmatch-to-sample recognition memory test or an object recognition memory task based on the animal's spontaneous preference for novelty. In the test period of both tasks, the preferred theta phase exhibited by CA1 pyramidal cells differed between moments when the rat inspected repeated (match) and non-repeated (nonmatch) items. Also in the present study, additional modeling work extended the previous model to address the mean phase of CA1 spiking associated with stimuli inducing varying levels of retrieval relative to encoding, ranging from novel nonmatch stimuli with no retrieval to highly familiar repeated stimuli with extensive retrieval. The modeling results obtained here demonstrated that the experimentally observed phase differences are consistent with different levels of CA3 synaptic input to CA1 during recognition of repeated items.     

编码与提取干扰对内隐和外显记忆的非对称性影响

以往研究表明在外显记忆中,编码与提取加工存在着非对称性,但在内隐记忆中,二者的关系并不明确,因此实验采用“学习-再认”范式,考察在编码或提取中分别附加的干扰任务对词汇判断或再认产生的影响。结果证实编码与提取干扰对内隐或外显记忆都具有非对称性的影响,但又存在着差异,即编码干扰会导致随后外显记忆成绩显著减少,而提取干扰对其影响较小,相反,编码干扰对随后内隐测验中启动效应的影响较小,但提取干扰会破坏启动效应,从而为内隐记忆和外显记忆的分离提供了进一步的证据     

Perirhinal cortex muscarinic receptor blockade impairs taste recognition memory formation

The relevance of perirhinal cortical cholinergic and glutamatergic neurotransmission for taste recognition memory and learned taste aversion was assessed by microinfusions of muscarinic (scopolamine), NMDA (AP-5), and AMPA (NBQX) receptor antagonists. Infusions of scopolamine, but not AP5 or NBQX, prevented the consolidation of taste recognition memory using attenuation of neophobia as an index. In addition, learned taste aversion in both short- and long-term memory tests was exclusively impaired by scopolamine. These data provide neurochemical support for the theory that cholinergic activity of the perirhinal cortex participates in the formation of the taste memory trace and that it is independent of the NMDA and AMPA receptor activity. These results support the idea that cholinergic neurotransmission in the perirhinal cortex is also essential for acquisition and consolidation of taste recognition memory.     

A temporally distinct role for group I and group II metabotropic glutamate receptors in object recognition memory

Recognition memory, involving the ability to discriminate between a novel and familiar object, depends on the integrity of the perirhinal cortex (PRH). Glutamate, the main excitatory neurotransmitter in the cortex, is essential for many types of memory processes. Of the subtypes of glutamate receptor, metabotropic receptors (mGluRs) have received less study than NMDA receptors; thus, the reported experiments examined the role of mGluRs in familiarity discrimination in the rat PRH. Experiments 1 and 2 assessed the effects of systemic administration of MPEP, a group I mGluR (specifically mGluR5) antagonist, and/or LY341495, a group II mGluR antagonist, on a spontaneous object novelty preference task. Simultaneous antagonism of both group I and II mGluRs impaired familiarity discrimination following a 24-h but not a 15-min delay, while antagonism of either mGluR subtype alone had no effect at either delay. The impairment was in acquisition, as in Experiment 3 coadministration of MPEP and LY341495 did not affect recognition memory performance when administered either after the sample phase or prior to test. The impairment in long-term recognition memory was mediated by mGluRs in the PRH, as localized intracortical antagonism of group I and II mGluRs also produced a deficit (Experiment 4). No evidence was found for an involvement of group III mGluRs in the acquisition of long-term familiarity discrimination (Experiment 5). These findings establish that glutamatergic neurotransmission in the PRH via group I and II mGluRs is crucial for the acquisition, but not for the consolidation or retrieval of long-term object recognition memory.     

物体颜色对情景记忆的影响

本研究采用ERP技术和学习-再认范式考察视觉输入的颜色和记忆中的物体颜色知识一致性对情景记忆编码和提取的影响。结果显示, 在对物体图片进行编码时颜色不一致图片诱发更大N400, 而提取阶段则对颜色一致图片有更多熟悉性加工(实验1); 物体名称能够更快激活典型颜色知识, 对颜色一致名称有更多细节回想(LPC更正) (实验2)。实验结果表明, 颜色一致促进知觉水平的记忆编码, 而阻碍语义水平编码。同时, 颜色一致促进物体图片提取(知觉水平)中的熟悉性和回想过程; 而对物体名称提取(概念水平)的促进作用仅表现在回想上。此外, 颜色与物体名称有着密切联系, 同样影响物体的语义表征, 支持激活-扩散模型理论。本研究从知觉和概念水平上为揭示物体颜色在联结记忆中的作用提供了证据。     

The effects of direction similarity in visual working memory: Behavioural and event-related potential studies

Object similarity can improve visual working memory (VWM) performance in the change-detection task, but impair the recognition performance when it occurs at retrieval of VWM in the recognition task. The effect of direction similarity is an issue that has not been well resolved. Furthermore, electrophysiological evidence in support of the mechanisms that underlie the effects of similarity is still scarce. In the current study, we conducted three behavioural experiments to examine the effects of direction similarity on memory performance with regard to both the encoding and retrieval phases of VWM and one event-related potential (ERP) experiment to explore the neural signatures of direction similarity in VWM. Our behavioural studies indicated that direction similarity improved performance when it occurred at the encoding phase but impaired performance when it occurred at the retrieval phase. Moreover, the ERP experiment showed that the amplitude of the contralateral delay activity (CDA) increased with the increasing set size for similar but not dissimilar directions. In addition, the CDA amplitude for similar directions was lower than that for dissimilar directions at set size 2. Taken together, these findings suggest that direction similarity at encoding has a positive effect on VWM performance and at retrieval has a negative effect. Given that VWM capacity depends on information load and the number of objects, the positive effect of similarity may be attributed to reduced information load of memory objects.     

Fearful expressions enhance recognition memory: electrophysiological evidence

Facial expressions play a key role in affective and social behavior. However, the temporal dynamics of the brain responses to emotional faces remain still unclear, in particular an open question is at what stage of face processing expressions might influence encoding and recognition memory. To try and answer this question we recorded the event-related potentials (ERPs) elicited in an old/new recognition task. A novel aspect of the present design was that whereas faces were presented during the study phase with either a happy, fearful or neutral expression, they were always neutral during the memory retrieval task. The ERP results showed three main findings: An enhanced early fronto-central positivity for faces encoded as fearful, both during the study and the retrieval phase. During encoding subsequent memory (Dm effect) was influenced by emotion. At retrieval the early components P100 and N170 were modulated by the emotional expression of the face at the encoding phase. Finally, the later ERP components related to recognition memory were modulated by the previously encoded facial expressions. Overall, these results suggest that face recognition is modulated by top-down influences from brain areas associated with emotional memory, enhancing encoding and retrieval in particular for fearful emotional expressions.     

Sleep deprivation impairs object recognition in mice

Many studies in animals and humans suggest that sleep facilitates learning, memory consolidation, and retrieval. Moreover, sleep deprivation (SD) incurred after learning, impaired memory in humans, mice, rats, and hamsters. We investigated the importance of sleep and its timing in an object recognition task in OF1 mice subjected to 6h SD either immediately after the acquisition phase (0-6 SD) or 6h later (7-12 SD), and in corresponding undisturbed controls. Motor activity was continuously recorded with infrared sensors. All groups explored two familiar, previously encountered objects to a similar extent, both at the end of the acquisition phase and 24h later during the test phase, indicating intact familiarity detection. During the test phase 0-6 SD mice failed to discriminate between the single novel and the two familiar objects. In contrast, the 7-12 SD group and the two control groups explored the novel object significantly longer than the two familiar objects. Plasma corticosterone levels determined after SD did not differ from time-matched undisturbed controls, but were significantly below the level measured after learning alone. ACTH did not differ between the groups. Therefore, it is unlikely that stress contributed to the memory impairment. We conclude that the loss of sleep and the activities the mice engaged in during the SD, impaired recognition memory retrieval, when they occurred immediately after acquisition. The delayed SD enabled memory consolidation during the 6h when the mice were allowed to sleep, and had no detrimental effect on memory. Neither SD schedule impaired object familiarity processing, suggesting that only specific cognitive abilities were sensitive to the intervention. Sleep may either actively promote memory formation, or alternatively, sleep may provide optimal conditions of non-interference for consolidation.     

提取干扰对内隐记忆的影响

以往研究多认同内隐记忆不会受到干扰的影响,但主要集中于编码时的干扰不会影响随后的内隐记忆提取成绩,而对于提取时的干扰是否也不会影响内隐记忆成绩仍存在疑义。该文在实验1采用学习-测验范式,通过在提取阶段设置同时干扰任务进一步考察提取干扰与内隐记忆的关系,结果表明提取干扰下并未发现明显的启动效应,即提取干扰破坏了内隐记忆。为进一步探讨内隐记忆的提取干扰效应是否源于记忆与干扰刺激同时呈现所引起的知觉表征竞争,实验2改变了记忆与干扰刺激的呈现顺序,结果表明不论干扰刺激在记忆项目之前或之后呈现,启动效应均受到影响。相比之下,提取干扰对再认成绩的影响并不明显(实验3)。上述结果表明,内隐记忆的提取干扰效应是源于一般认知资源的竞争,在提取过程中任何能够产生认知资源竞争的变量设置都可能会削减内隐测验中的启动效应。     

rTMS stimulation on left DLPFC increases the correct recognition of memories for emotional target and distractor words

According to a recent hypothesis, the prefrontal cortex has been proposed as the site of emotional memory integration, because it is sensitive to the recognition of emotional contents. In the present research, we explored the role of the dorsolateral prefrontal cortex (DLPFC) in memory recognition processes for positive versus negative emotional stimuli when old (target) and new (distractor, either semantically related or unrelated to the target) stimuli were presented. The role of the DLPFC was analysed using an rTMS (repeated transcranial magnetic stimulation) paradigm that induced increased cortical activation of the left DLPFC. The subjects were required to perform a task that consisted of two experimental phases (i.e., an encoding and a recognition phase) in which the targets and the distractors were presented and recognition performance was measured. rTMS stimulation was provided over the left DLPFC during the recognition phase. We found that the rTMS stimulation affected the memory recognition of positive emotional material. Moreover, related and unrelated distractors were discarded better when they were positively valenced, and a more significant effect (i.e., increased performance) was produced in response to related distractors. This result suggests that the activation of the left DLPFC favours the memory recognition of positive emotional information, and that such activation is able to induce a more appropriate selective process to distinguish target from distractor stimuli in the presence of more complex processes (related distractors). The valence model of emotional cue processing may explain this increased performance by demonstrating the distinct role of the left hemisphere in the retrieval of positive emotional information.     

Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory

Evidence indicates that brain endocannabinoids are involved in memory processing. However, the participation of CB1 and CB2 cannabinoid receptors in recognition memory has not been yet conclusively determined. Therefore, we evaluated the effect of the posttraining activation of hippocampal cannabinoid receptors on the consolidation of object recognition memory. Rats with infusion cannulae stereotaxically aimed to the CA1 region of the dorsal hippocampus were trained in an object recognition learning task involving exposure to two different stimulus objects. Memory retention was assessed at different times after training. In the test sessions, one of the objects presented during training was replaced by a novel one. When infused in the CA1 region immediately after training, the non-selective cannabinoid receptor agonist WIN-55,212-2 and the endocannabinoid membrane transporter inhibitor VDM-11 blocked long-term memory retention in a dose-dependent manner without affecting short-term memory, exploratory behavior, anxiety state or the functionality of the hippocampus. The amnesic effect of WIN-55,212-2 and VDM-11 was not due to state-dependency and was completely reversed by co-infusion of the CB1 receptor antagonist AM-251 and mimicked by the CB1 receptor agonist ACEA but not by the CB2 receptor agonists JWH-015 and palmitoylethanolamide. Our data indicate that activation of hippocampal CB1 receptors early after training hampers consolidation of object recognition memory.     

(-)-9-Dehydrogalanthaminium bromide,a new cholinesterase inhibitor,enhances place and object recognition memory in young and old rats

In a previous study, we showed that (-)-9-dehydrogalanthaminium bromide, a synthetic galanthamine derivative, was more potent than galanthamine in inhibiting acetylcholinesterase. We studied here the action of this new compound on recognition memory in young and old rats, using a two-trial recognition task designed to test both place and object recognition. (-)-9-dehydrogalanthaminium bromide was injected (0.3, 1, and 3 mg/kg, i.p.) in young and old rats before the acquisition phase, immediately after it, or before the retrieval phase of the task, in order to determine the stage of information processing affected by the compound. (-)-9-dehydrogalanthaminium bromide improved both place and object recognition in young rats, via an enhancement of acquisition (3 mg/kg: place recognition; 1 and 3 mg/kg: object recognition) and consolidation (1 and 3 mg/kg) information processing. In old rats, (-)-9-dehydrogalanthaminium bromide improved performance by acting on the acquisition processes of place (0.3, 1, and 3 mg/kg) and object (1 and 3 mg/kg) recognition. These results provide information on the profile of activity of (-)-9-dehydrogalanthaminium bromide on memory processes, and suggest that this new compound could have utility in the treatment of cognitive dysfunction occurring in Alzheimer's disease or in the normal course of aging.     

The effects of physical activity timing and complexity on episodic memory: A randomized controlled trial

The role of two types of acute physical activity (PA) bouts were assessed on young adults’ free-recall and recognition memory in two experiments, which differed in the temporal relation of PA and word encoding. Before or following training on the Rey Auditory Verbal Learning Task, participants performed a simple two-step dance, a complex four-step dance, or remained seated. Hypotheses proposed that PA prior to encoding and complex PA would enhance PA’s mnemonic benefits. Memory assessed post-PA, 24 h, and 7 days after training indicated that timing and complexity of PA did not impact free-recall or recognition memory. Findings differ from a previous study showing complex PA benefited motor learning more than simple PA (Tomporowski & Pendleton, 2018). The inconsistency may be due to different working memory processes underlying consolidation and retrieval of procedural or episodic information. Theory-based explanations regarding memory storage and retrieval are proposed to elucidate this selective process.     

On the role of hippocampal protein synthesis in the consolidation and reconsolidation of object recognition memory

Upon retrieval, consolidated memories are again rendered vulnerable to the action of metabolic blockers, notably protein synthesis inhibitors. This has led to the hypothesis that memories are reconsolidated at the time of retrieval, and that this depends on protein synthesis. Ample evidence indicates that the hippocampus plays a key role both in the consolidation and reconsolidation of different memories. Despite this fact, at present there are no studies about the consequences of hippocampal protein synthesis inhibition in the storage and post-retrieval persistence of object recognition memory. Here we report that infusion of the protein synthesis inhibitor anisomycin in the dorsal CA1 region immediately or 180 min but not 360 min after training impairs consolidation of long-term object recognition memory without affecting short-term memory, exploratory behavior, anxiety state, or hippocampal functionality. When given into CA1 after memory reactivation in the presence of familiar objects, ANI did not affect further retention. However, when administered into CA1 immediately after exposing animals to a novel and a familiar object, ANI impaired memory of both of them. The amnesic effect of ANI was long-lasting, did not happen after exposure to two novel objects, following exploration of the context alone, or in the absence of specific stimuli, suggesting that it was not reversible but was contingent on the reactivation of the consolidated trace in the presence of a salient, behaviorally relevant novel cue. Our results indicate that hippocampal protein synthesis is required during a limited post-training time window for consolidation of object recognition memory and show that the hippocampus is engaged during reconsolidation of this type of memory, maybe accruing new information into the original trace.