Learning & memory (Cold Spring Harbor, N.Y.)最新文献

{"title":"Overcoming interference: an fMRI investigation of pattern separation in the medial temporal lobe.","authors":"C Brock Kirwan,&nbsp;Craig E L Stark","doi":"10.1101/lm.663507","DOIUrl":"https://doi.org/10.1101/lm.663507","url":null,"abstract":"<p><p>The medial temporal lobe (MTL) supports the formation and retrieval of long-term declarative memories, or memories for facts and everyday events. One challenge posed for this type of memory stems from the highly overlapping nature of common episodes. Within cognitive psychology, it is widely accepted that interference between information learned at different times is a major limitation on memory. In spite of several decades of intense research in the fields of interference theory and the neurobiological underpinnings of declarative memory, there is little direct evidence bearing on how the MTL resolves this interference to form accurate memories of everyday facts and events. Computational models of MTL function have proposed a mechanism in which the MTL, specifically the hippocampus, performs pattern separation, whereby overlapping representations are made less similar. However, there is little evidence bearing on how this process is carried out in the intact human MTL. Using high-resolution fMRI, we conducted a set of experiments that taxed behavioral pattern separation by using highly similar, interfering stimuli in a modified continuous recognition task. Regions within the parahippocampal gyrus demonstrated activity consistent with a \"recall to reject\" strategy. In contrast and critical to performing the task, activity within the hippocampus distinguished between correctly identified true stimulus repetitions, correctly rejected presentations of similar lure stimuli, and false alarms to similar lures. These data support the computational models' assertion that the hippocampus plays a key role in pattern separation.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"625-33"},"PeriodicalIF":2.0,"publicationDate":"2007-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.663507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40957086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha3-integrins are required for hippocampal long-term potentiation and working memory.","authors":"Chi-Shing Chan,&nbsp;Jonathan M Levenson,&nbsp;Partha S Mukhopadhyay,&nbsp;Lin Zong,&nbsp;Allan Bradley,&nbsp;J David Sweatt,&nbsp;Ronald L Davis","doi":"10.1101/lm.648607","DOIUrl":"https://doi.org/10.1101/lm.648607","url":null,"abstract":"Integrins comprise a large family of heterodimeric, transmembrane cell adhesion receptors that mediate diverse neuronal functions in the developing and adult CNS. Recent pharmacological and genetic studies have suggested that β1-integrins are critical in synaptic plasticity and memory formation. To further define the role of integrins in these processes, we generated a postnatal forebrain and excitatory neuron-specific knockout of α3-integrin, one of several binding partners for β1 subunit. At hippocampal Schaffer collateral-CA1 synapses, deletion of α3-integrin resulted in impaired long-term potentiation (LTP). Basal synaptic transmission and paired-pulse facilitation were normal in the absence of α3-integrin. Behavioral studies demonstrated that the mutant mice were selectively defective in a hippocampus-dependent, nonmatch-to-place working memory task, but were normal in other hippocampusdependent spatial tasks. The impairment in LTP and working memory is similar to that observed in β1-integrin conditional knockout mice, suggesting that α3-integrin is the functional binding partner for β1 for these processes in the forebrain.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"606-15"},"PeriodicalIF":2.0,"publicationDate":"2007-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.648607","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40957084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct prefrontal molecular mechanisms for information storage lasting seconds versus minutes.","authors":"Jason D Runyan,&nbsp;Pramod K Dash","doi":"10.1101/lm.92405","DOIUrl":"https://doi.org/10.1101/lm.92405","url":null,"abstract":"<p><p>The prefrontal cortex (PFC) is known to actively hold information \"online\" for a period of seconds in working memory for guiding goal-directed behavior. It has been proposed that relevant information is stored in other brain regions, which is retrieved and held in working memory for subsequent assimilation by the PFC in order to guide behavior. It is uncertain whether PFC stores information outside the temporal limits of working memory. Here, we demonstrate that although enhanced cAMP-dependent protein kinase A (PKA) activity in the PFC is detrimental to working memory, it is required for performance in tasks involving conflicting representations when memory storage is needed for minutes. This study indicates that distinct molecular mechanisms within the PFC underlie information storage for seconds (working memory) and for minutes (short-term memory). In addition, our results demonstrate that short-term memory storage within the prefrontal cortex is required for guiding behavior in tasks with conflicts and provides a plausible mechanism by which the prefrontal cortex executes cognitive control.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"232-8"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.92405","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40943765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pontine stimulation overcomes developmental limitations in the neural mechanisms of eyeblink conditioning.","authors":"John H Freeman,&nbsp;Christine A Rabinak,&nbsp;Matthew M Campolattaro","doi":"10.1101/lm.91105","DOIUrl":"https://doi.org/10.1101/lm.91105","url":null,"abstract":"<p><p>Pontine neuronal activation during auditory stimuli increases ontogenetically between postnatal days (P) P17 and P24 in rats. Pontine neurons are an essential component of the conditioned stimulus (CS) pathway for eyeblink conditioning, providing mossy fiber input to the cerebellum. Here we examined whether the developmental limitation in pontine responsiveness to a CS in P17 rats could be overcome by direct stimulation of the CS pathway. Eyeblink conditioning was established in infant rats on P17-P18 and P24-P25 using pontine stimulation as a CS. There were no significant age-related differences in the rate or level of conditioning. Eyeblink conditioned responses established with the stimulation CS were abolished by inactivation of the ipsilateral cerebellar nuclei and overlying cortex in both age groups. The findings suggest that developmental changes in the CS pathway play an important role in the ontogeny of eyeblink conditioning.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"255-9"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.91105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40943768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The L-type calcium channel blocker nifedipine impairs extinction, but not reduced contingency effects, in mice.","authors":"Christopher K Cain,&nbsp;Bill P Godsil,&nbsp;Shekib Jami,&nbsp;Mark Barad","doi":"10.1101/lm.88805","DOIUrl":"https://doi.org/10.1101/lm.88805","url":null,"abstract":"<p><p>We recently reported that fear extinction, a form of inhibitory learning, is selectively blocked by systemic administration of L-type voltage-gated calcium channel (LVGCC) antagonists, including nifedipine, in mice. We here replicate this finding and examine three reduced contingency effects after vehicle or nifedipine (40 mg/kg) administration. In the first experiment, contingency reduction was achieved by adding USs to the training protocol (degraded contingency), a phenomenon thought to be independent of behavioral inhibition. In the second experiment, contingency reduction was achieved by varying the percentage of CS-US pairing, a phenomenon thought to be weakly dependent on behavioral inhibition. In the third and fourth experiments, contingency reduction was achieved by adding CSs to the training protocol (partial reinforcement), a phenomenon thought to be completely dependent on behavioral inhibition. We found that none of these reduced contingency effects was impaired by nifedipine. In a final experiment, we found that extinction conducted 1 or 3 h post-acquisition, but not immediately, was LVGCC-dependent. Taken together, the results suggest that reduced contingency effects and extinction depend on different molecular mechanisms and that LVGCC dependence of behavioral inhibition develops with time after associative CS-US learning.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"277-84"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.88805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40943770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ablation of cerebellar nuclei prevents H-reflex down-conditioning in rats.","authors":"Xiang Yang Chen,&nbsp;Jonathan R Wolpaw","doi":"10.1101/lm.91305","DOIUrl":"https://doi.org/10.1101/lm.91305","url":null,"abstract":"<p><p>While studies of cerebellar involvement in learning and memory have described plasticity within the cerebellum, its role in acquisition of plasticity elsewhere in the CNS is largely unexplored. This study set out to determine whether the cerebellum is needed for acquisition of the spinal cord plasticity that underlies operantly conditioned decrease in the H-reflex, the electrical analog of the spinal stretch reflex. Rats in which the cerebellar output nuclei dentate and interpositus (DIN) had been ablated were exposed for 50 d to the H-reflex down-conditioning protocol. DIN ablation, which in itself had no significant long-term effect on H-reflex size, entirely prevented acquisition of a smaller H-reflex. Since previous studies show that corticospinal tract (CST) transection also prevents down-conditioning while transection of the rubrospinal tract and other major descending tracts does not, this result implies that DIN output that affects cortex is essential for generation of the CST activity that induces the spinal cord plasticity, which is, in turn, directly responsible for the smaller H-reflex. The result extends the role of the cerebellum in learning and memory to include participation in induction of plasticity elsewhere in the CNS, specifically in the spinal cord. The cerebellum might simply support processes in sensorimotor cortex or elsewhere that change the spinal cord, or the cerebellum itself might undergo plasticity similar to that occurring with vestibulo-ocular reflex (VOR) or eyeblink conditioning.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"248-54"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.91305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40943767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPA/kainate, NMDA, and dopamine D1 receptor function in the nucleus accumbens core: a context-limited role in the encoding and consolidation of instrumental memory.","authors":"Pepe J Hernandez,&nbsp;Matthew E Andrzejewski,&nbsp;Kenneth Sadeghian,&nbsp;Jules B Panksepp,&nbsp;Ann E Kelley","doi":"10.1101/lm.93105","DOIUrl":"https://doi.org/10.1101/lm.93105","url":null,"abstract":"<p><p>Neural integration of glutamate- and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of learning (acquisition or consolidation) these receptors are recruited, nor is it known what role AMPA/kainate receptors have in these processes. Here we show that pre-trial intra-NAc core administration of the NMDA, AMPA/KA, and D1 receptor antagonists AP-5 (1 microg/0.5 microL), LY293558 (0.01 or 0.1 microg/0.5 microL), and SCH23390 (1 microg/0.5 microL), respectively, impaired acquisition of a lever-pressing response, whereas post-trial administration left memory consolidation unaffected. An analysis of the microstructure of behavior while rats were under the influence of these drugs revealed that glutamatergic and dopaminergic signals contribute differentially to critical aspects of the initial, randomly emitted behaviors that enable reinforcement learning. Thus, glutamate and dopamine receptors are activated in a time-limited fashion-only being required while the animals are actively engaged in the learning context.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"285-95"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.93105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40942538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrolytic lesions of the dorsal hippocampus disrupt renewal of conditional fear after extinction.","authors":"Jinzhao Ji,&nbsp;Stephen Maren","doi":"10.1101/lm.91705","DOIUrl":"https://doi.org/10.1101/lm.91705","url":null,"abstract":"<p><p>There is a growing body of evidence that the hippocampus is critical for context-dependent memory retrieval. In the present study, we used Pavlovian fear conditioning in rats to examine the role of the dorsal hippocampus (DH) in the context-specific expression of fear memory after extinction (i.e., renewal). Pre-training electrolytic lesions of the DH blunted the expression of conditional freezing to an auditory conditional stimulus (CS), but did not affect the acquisition of extinction to that CS. In contrast, DH lesions impaired the context-specific expression of extinction, eliminating the renewal of fear normally observed to a CS presented outside of the extinction context. Post-extinction DH lesions also eliminated the context dependence of fear extinction. These results are consistent with those using pharmacological inactivation of the DH and suggest that the DH is required for using contextual stimuli to regulate the expression of fear to a Pavlovian CS after extinction.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"270-6"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.91705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40943769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of the rat anterior cingulate cortex in control of instrumental responses guided by reward expectancy.","authors":"Judith Schweimer,&nbsp;Wolfgang Hauber","doi":"10.1101/lm.90605","DOIUrl":"https://doi.org/10.1101/lm.90605","url":null,"abstract":"<p><p>The anterior cingulate cortex (ACC) plays a critical role in stimulus-reinforcement learning and reward-guided selection of actions. Here we conducted a series of experiments to further elucidate the role of the ACC in instrumental behavior involving effort-based decision-making and instrumental learning guided by reward-predictive stimuli. In Experiment 1, rats were trained on a cost-benefit T-maze task in which they could either choose to climb a barrier to obtain a high reward (four pellets) in one arm or a low reward (two pellets) in the other with no barrier present. In line with previous studies, our data reveal that rats with quinolinic acid lesions of the ACC selected the response involving less work and smaller reward. Experiment 2 demonstrates that breaking points of instrumental performance under a progressive ratio schedule were similar in sham-lesioned and ACC-lesioned rats. Thus, lesions of the ACC did not interfere with the effort a rat is willing to expend to obtain a specific reward in this test. In a subsequent task, we examined effort-based decision-making in a lever-press task where rats had the choice between pressing a lever to receive preferred food pellets under a progressive ratio schedule, or free feeding on a less preferred food, i.e. lab chow. Results show that sham- and ACC-lesioned animals had similar breaking points and ingested comparable amounts of less-preferred food. Together, the results of Experiment 1 and 2 suggest that the ACC plays a role in evaluating how much effort to expend for reward; however, the ACC is not necessary in all situations requiring an assessment of costs and benefits. In Experiment 3 we investigated learning and reversal learning of instrumental responses guided by reward predictive stimuli. A reaction time (RT) task demanding conditioned lever release was used in which the upcoming reward magnitude (five vs. one food pellet) was signalled in advance by discriminative visual stimuli. Results revealed that rats with ACC lesions were able to discriminate reward magnitude-predictive stimuli and to adapt instrumental behavior to reversed stimulus-reward magnitude contingencies. Thus, in a simple discrimination task as used here, the ACC appears not to be required to discriminate reward magnitude-predictive stimuli and to use the learned significance of the stimuli to guide instrumental behavior.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"334-42"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.90605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40942540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping neuronal activation and the influence of adrenergic signaling during contextual memory retrieval.","authors":"Wei-Ping Zhang,&nbsp;John F Guzowski,&nbsp;Steven A Thomas","doi":"10.1101/lm.90005","DOIUrl":"https://doi.org/10.1101/lm.90005","url":null,"abstract":"<p><p>We recently described a critical role for adrenergic signaling in the hippocampus during contextual and spatial memory retrieval. To determine which neurons are activated by contextual memory retrieval and its sequelae in the presence and absence of adrenergic signaling, transcriptional imaging for the immediate-early gene Arc was used in control and mutant mice lacking norepinephrine and epinephrine. This imaging approach permits the identification of neuronal genomic activation specific to one of two behavioral epochs in the same animal. Analysis revealed several brain regions that were more greatly activated by re-exposure to a salient versus neutral context 1 d after training in control mice (e.g., hippocampal CA3 and CA1, the amygdala, the dorsolateral caudate/putamen, the primary motor cortex, and parts of the rhinal cortices). In mice lacking norepinephrine and epinephrine, many of these regions exhibited significantly reduced activation (e.g., hippocampal CA1), while other regions did not (e.g., hippocampal CA3). In consideration with previous results, the current findings suggest a hypothesis in which adrenergic signaling may be critical for the transfer of retrieved contextual information from CA3 to CA1, where it would be compared to online sensory information coming directly from the cortex.</p>","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"239-47"},"PeriodicalIF":2.0,"publicationDate":"2005-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.90005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40943766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}