Learning & memory (Cold Spring Harbor, N.Y.)最新文献_第7页

Average group behavior does not represent individual behavior in classical conditioning of the honeybee. 在蜜蜂的经典条件作用中，平均群体行为并不代表个体行为。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-10-31 Print Date: 2011-11-01 DOI: 10.1101/lm.2232711

Evren Pamir, Neloy Kumar Chakroborty, Nicola Stollhoff, Katrin Barbara Gehring, Victoria Antemann, Laura Morgenstern, Johannes Felsenberg, Dorothea Eisenhardt, Randolf Menzel, Martin Paul Nawrot

{"title":"Average group behavior does not represent individual behavior in classical conditioning of the honeybee.","authors":"Evren Pamir, Neloy Kumar Chakroborty, Nicola Stollhoff, Katrin Barbara Gehring, Victoria Antemann, Laura Morgenstern, Johannes Felsenberg, Dorothea Eisenhardt, Randolf Menzel, Martin Paul Nawrot","doi":"10.1101/lm.2232711","DOIUrl":"https://doi.org/10.1101/lm.2232711","url":null,"abstract":"Conditioned behavior as observed during classical conditioning in a group of identically treated animals provides insights into the physiological process of learning and memory formation. However, several studies in vertebrates found a remarkable difference between the group-average behavioral performance and the behavioral characteristics of individual animals. Here, we analyzed a large number of data (1640 animals) on olfactory conditioning in the honeybee (Apis mellifera). The data acquired during absolute and differential classical conditioning differed with respect to the number of conditioning trials, the conditioned odors, the intertrial intervals, and the time of retention tests. We further investigated data in which animals were tested for spontaneous recovery from extinction. In all data sets we found that the gradually increasing group-average learning curve did not adequately represent the behavior of individual animals. Individual behavior was characterized by a rapid and stable acquisition of the conditioned response (CR), as well as by a rapid and stable cessation of the CR following unrewarded stimuli. In addition, we present and evaluate different model hypotheses on how honeybees form associations during classical conditioning by implementing a gradual learning process on the one hand and an all-or-none learning process on the other hand. In summary, our findings advise that individual behavior should be recognized as a meaningful predictor for the internal state of a honeybee--irrespective of the group-average behavioral performance.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"733-41"},"PeriodicalIF":2.0,"publicationDate":"2011-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.2232711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40118573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 49

Differing time dependencies of object recognition memory impairments produced by nicotinic and muscarinic cholinergic antagonism in perirhinal cortex. 烟碱胆碱能拮抗剂和毒蕈碱胆碱能拮抗剂在嗅周皮层引起的物体识别记忆障碍的不同时间依赖性。

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-06-21 Print Date: 2011-01-01 DOI: 10.1101/lm.2274911

Chris J Tinsley, Nadine S Fontaine-Palmer, Maria Vincent, Emma P E Endean, John P Aggleton, Malcolm W Brown, E Clea Warburton

{"title":"Differing time dependencies of object recognition memory impairments produced by nicotinic and muscarinic cholinergic antagonism in perirhinal cortex.","authors":"Chris J Tinsley, Nadine S Fontaine-Palmer, Maria Vincent, Emma P E Endean, John P Aggleton, Malcolm W Brown, E Clea Warburton","doi":"10.1101/lm.2274911","DOIUrl":"10.1101/lm.2274911","url":null,"abstract":"The roles of muscarinic and nicotinic cholinergic receptors in perirhinal cortex in object recognition memory were compared. Rats' discrimination of a novel object preference test (NOP) test was measured after either systemic or local infusion into the perirhinal cortex of the nicotinic receptor antagonist methyllycaconitine (MLA), which targets alpha-7 (α7) amongst other nicotinic receptors or the muscarinic receptor antagonists scopolamine, AFDX-384, and pirenzepine. Methyllycaconitine administered systemically or intraperirhinally before acquisition impaired recognition memory tested after a 24-h, but not a 20-min delay. In contrast, all three muscarinic antagonists produced a similar, unusual pattern of impairment with amnesia after a 20-min delay, but remembrance after a 24-h delay. Thus, the amnesic effects of nicotinic and muscarinic antagonism were doubly dissociated across the 20-min and 24-h delays. The same pattern of shorter-term but not longer-term memory impairment was found for scopolamine whether the object preference test was carried out in a square arena or a Y-maze and whether rats of the Dark Agouti or Lister-hooded strains were used. Coinfusion of MLA and either scopolamine or AFDX-384 produced an impairment profile matching that for MLA. Hence, the antagonists did not act additively when coadministered. These findings establish an important role in recognition memory for both nicotinic and muscarinic cholinergic receptors in perirhinal cortex, and provide a challenge to simple ideas about the role of cholinergic processes in recognition memory: The effects of muscarinic and nicotinic antagonism are neither independent nor additive.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"484-92"},"PeriodicalIF":0.0,"publicationDate":"2011-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125612/pdf/TinsleyLM22749.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29953503","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}

引用次数: 0

Differential dependence of Pavlovian incentive motivation and instrumental incentive learning processes on dopamine signaling. 巴甫洛夫激励动机和工具性激励学习过程对多巴胺信号的差异依赖。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-06-21 Print Date: 2011-01-01 DOI: 10.1101/lm.2229311

Kate M Wassum, Sean B Ostlund, Bernard W Balleine, Nigel T Maidment

{"title":"Differential dependence of Pavlovian incentive motivation and instrumental incentive learning processes on dopamine signaling.","authors":"Kate M Wassum, Sean B Ostlund, Bernard W Balleine, Nigel T Maidment","doi":"10.1101/lm.2229311","DOIUrl":"https://doi.org/10.1101/lm.2229311","url":null,"abstract":"Here we attempted to clarify the role of dopamine signaling in reward seeking. In Experiment 1, we assessed the effects of the dopamine D(1)/D(2) receptor antagonist flupenthixol (0.5 mg/kg i.p.) on Pavlovian incentive motivation and found that flupenthixol blocked the ability of a conditioned stimulus to enhance both goal approach and instrumental performance (Pavlovian-to-instrumental transfer). In Experiment 2 we assessed the effects of flupenthixol on reward palatability during post-training noncontingent re-exposure to the sucrose reward in either a control 3-h or novel 23-h food-deprived state. Flupenthixol, although effective in blocking the Pavlovian goal approach, was without effect on palatability or the increase in reward palatability induced by the upshift in motivational state. This noncontingent re-exposure provided an opportunity for instrumental incentive learning, the process by which rats encode the value of a reward for use in updating reward-seeking actions. Flupenthixol administered prior to the instrumental incentive learning opportunity did not affect the increase in subsequent off-drug reward-seeking actions induced by that experience. These data suggest that although dopamine signaling is necessary for Pavlovian incentive motivation, it is not necessary for changes in reward experience, or for the instrumental incentive learning process that translates this experience into the incentive value used to drive reward-seeking actions, and provide further evidence that Pavlovian and instrumental incentive learning processes are dissociable.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"475-83"},"PeriodicalIF":2.0,"publicationDate":"2011-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.2229311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29953502","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}

引用次数: 127

Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning. 纹状体神经元中腺苷A(2A)受体的选择性失活增强了工作记忆和逆向学习。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-06-21 Print Date: 2011-01-01 DOI: 10.1101/lm.2136011

Catherine J Wei, Philipp Singer, Joana Coelho, Detlev Boison, Joram Feldon, Benjamin K Yee, Jiang-Fan Chen

{"title":"Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning.","authors":"Catherine J Wei, Philipp Singer, Joana Coelho, Detlev Boison, Joram Feldon, Benjamin K Yee, Jiang-Fan Chen","doi":"10.1101/lm.2136011","DOIUrl":"https://doi.org/10.1101/lm.2136011","url":null,"abstract":"The adenosine A(2A) receptor (A(2A)R) is highly enriched in the striatum where it is uniquely positioned to integrate dopaminergic, glutamatergic, and other signals to modulate cognition. Although previous studies support the hypothesis that A(2A)R inactivation can be pro-cognitive, analyses of A(2A)R's effects on cognitive functions have been restricted to a small subset of cognitive domains. Furthermore, the relative contribution of A(2A)Rs in distinct brain regions remains largely unknown. Here, we studied the regulation of multiple memory processes by brain region-specific populations of A(2A)Rs. Specifically, we evaluated the cognitive impacts of conditional A(2A)R deletion restricted to either the entire forebrain (i.e., cerebral cortex, hippocampus, and striatum, fb-A(2A)R KO) or to striatum alone (st-A(2A)R KO) in recognition memory, working memory, reference memory, and reversal learning. This comprehensive, comparative analysis showed for the first time that depletion of A(2A)R-dependent signaling in either the entire forebrain or striatum alone is associated with two specific phenotypes indicative of cognitive flexibility-enhanced working memory and enhanced reversal learning. These selective pro-cognitive phenotypes seemed largely attributed to inactivation of striatal A(2A)Rs as they were captured by A(2A)R deletion restricted to striatal neurons. Neither spatial reference memory acquisition nor spatial recognition memory were grossly affected, and no evidence for compensatory changes in striatal or cortical D(1), D(2), or A(1) receptor expression was found. This study provides the first direct demonstration that targeting striatal A(2A)Rs may be an effective, novel strategy to facilitate cognitive flexibility under normal and pathologic conditions.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"459-74"},"PeriodicalIF":2.0,"publicationDate":"2011-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.2136011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29953501","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}

引用次数: 84

Nicotine trained as a negative feature passes the retardation-of-acquisition and summation tests of a conditioned inhibitor. 尼古丁作为一个负面特征训练通过了条件抑制剂的习得迟缓和求和测试。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-06-21 Print Date: 2011-01-01 DOI: 10.1101/lm.2177411

Jennifer E Murray, Andrew W Walker, Chia Li, Nicole R Wells, Rachel D Penrod, Rick A Bevins

{"title":"Nicotine trained as a negative feature passes the retardation-of-acquisition and summation tests of a conditioned inhibitor.","authors":"Jennifer E Murray, Andrew W Walker, Chia Li, Nicole R Wells, Rachel D Penrod, Rick A Bevins","doi":"10.1101/lm.2177411","DOIUrl":"https://doi.org/10.1101/lm.2177411","url":null,"abstract":"Nicotine functions as a negative feature in a Pavlovian discriminated goal-tracking task. Whether withholding of responding to the conditional stimulus (CS) reflects nicotine functioning as a conditioned inhibitor is unknown. Accordingly, the present research sought to determine whether nicotine trained as a negative feature passed the retardation-of-acquisition and summation tests, thus characterizing it as a pharmacological (interoceptive) conditioned inhibitor. In the retardation test, rats received either nicotine (0.4 mg/kg) or chlordiazepoxide (5 mg/kg) negative feature training in which the drug state signaled when a 15-sec light CS would not be paired with sucrose; light was paired with sucrose on intermixed saline sessions. Following acquisition of the discrimination, both groups received nicotine CS training in which sucrose was intermittently available on nicotine but not intermixed saline sessions. Acquisition of conditioned responding to the nicotine CS was slower in the nicotine negative feature group than in the chlordiazepoxide negative feature group. In the summation test, rats were assigned to either the nicotine negative feature group or a pseudoconditioning control. In this control, the light CS was paired with sucrose on half the nicotine and half the saline sessions. Both groups also received excitatory training in which a white noise CS was paired with sucrose. The summation test consisted of presenting the white noise in conjunction with nicotine. Conditioned responding evoked by the white noise was decreased in the negative feature but not the pseudoconditioning group. Combined, the results provide the first evidence that an interoceptive stimulus (nicotine) can become a conditioned inhibitor.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"452-8"},"PeriodicalIF":2.0,"publicationDate":"2011-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.2177411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29953500","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}

引用次数: 14

Contributions of dorsal striatal subregions to spatial alternation behavior. 背纹状体亚区对空间交替行为的贡献。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-06-17 Print Date: 2011-07-01 DOI: 10.1101/lm.2123811

Roula Moussa, Bruno Poucet, Marianne Amalric, Francesca Sargolini

{"title":"Contributions of dorsal striatal subregions to spatial alternation behavior.","authors":"Roula Moussa, Bruno Poucet, Marianne Amalric, Francesca Sargolini","doi":"10.1101/lm.2123811","DOIUrl":"https://doi.org/10.1101/lm.2123811","url":null,"abstract":"Considerable evidence has shown a clear dissociation between the dorsomedial (DMS) and the dorsolateral (DLS) striatum in instrumental conditioning. In particular, DMS activity is necessary to form action-outcome associations, whereas the DLS is required for developing habitual behavior. However, few studies have investigated whether a similar dissociation exists in more complex goal-directed learning processes. The present study examined the role of the two structures in such complex learning by analyzing the effects of excitotoxic DMS and DLS lesions during the acquisition and extinction of spatial alternation behavior, in a continuous alternation T-maze task. We demonstrate that DMS and DLS lesions have opposite effects, the former impairing and the latter improving animal performance during learning and extinction. DMS lesions may impair the acquisition of spatial alternation behavior by disrupting the signal necessary to link a goal with a specific spatial sequence. In contrast, DLS lesions may accelerate goal-driven strategies by minimizing the influence of external stimuli on the response, thus increasing the impact of action-reward contingencies. Taken together, these results suggest that DMS- and DLS-mediated learning strategies develop in parallel and compete for the control of the behavioral response early in learning.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"444-51"},"PeriodicalIF":2.0,"publicationDate":"2011-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.2123811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29947095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 58

Accumbens shell AMPA receptors mediate expression of extinguished reward seeking through interactions with basolateral amygdala. 伏隔壳AMPA受体通过与基底外侧杏仁核的相互作用介导消失的奖励寻求的表达。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-06-15 Print Date: 2011-07-01 DOI: 10.1101/lm.2144411

E Zayra Millan, Gavan P McNally

{"title":"Accumbens shell AMPA receptors mediate expression of extinguished reward seeking through interactions with basolateral amygdala.","authors":"E Zayra Millan, Gavan P McNally","doi":"10.1101/lm.2144411","DOIUrl":"https://doi.org/10.1101/lm.2144411","url":null,"abstract":"Extinction is the reduction in drug seeking when the contingency between drug seeking behavior and the delivery of drug reward is broken. Here, we investigated a role for the nucleus accumbens shell (AcbSh). Rats were trained to respond for 4% (v/v) alcoholic beer in one context (Context A) followed by extinction in a second context (Context B). Rats were subsequently tested in the training context, A (ABA), or the extinction context, B (ABB). Pre-test injections of the glutamate AMPA receptor antagonist, NBQX (1 µg) into AcbSh had no effect on renewal of alcoholic beer seeking when rats were returned to the training context (ABA). However, NBQX increased responding when rats were tested in the extinction context (ABB). In a second experiment, rats received training, extinction, and test in the same context. Pre-test injections of NBQX (0, 0.3, and 1 µg) into the AcbSh dose-dependently attenuated expression of extinction. We also found that NBQX in the AcbSh had no effect on initial acquisition of extinction or the motivation to respond for reward as measured by break point on a progressive ratio schedule. Finally, we show that pharmacological disconnection of a basolateral amygdala (BLA) → AcbSh pathway via NBQX in AcbSh combined with reversible inactivation of the contralateral BLA attenuates expression of extinction. Together, these results suggest that AcbSh AMPA receptors mediate expression of extinguished reward seeking through glutamatergic inputs from the BLA.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"414-21"},"PeriodicalIF":2.0,"publicationDate":"2011-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.2144411","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29939088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 44

Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training. Morris水迷宫中的空间和逆向学习在很大程度上抵抗训练后6小时的快速眼动睡眠剥夺。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-06-15 Print Date: 2011-07-01 DOI: 10.1101/lm.2099011

Christine M Walsh, Victoria Booth, Gina R Poe

{"title":"Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training.","authors":"Christine M Walsh, Victoria Booth, Gina R Poe","doi":"10.1101/lm.2099011","DOIUrl":"https://doi.org/10.1101/lm.2099011","url":null,"abstract":"This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation-associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"422-34"},"PeriodicalIF":2.0,"publicationDate":"2011-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/lm.2099011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29939090","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}

引用次数: 55

Independence of first- and second-order memories in newborn rabbits. 新生兔一、二级记忆的独立性。

IF 2

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-05-20 Print Date: 2011-06-01 DOI: 10.1101/lm.2145111

Gérard Coureaud, Solène Languille, Virginie Joly, Benoist Schaal, Bernard Hars

引用次数: 12

Insulin receptor substrate 2 is a negative regulator of memory formation. 胰岛素受体底物2是记忆形成的负调节因子。

Learning & memory (Cold Spring Harbor, N.Y.) Pub Date : 2011-05-19 Print Date: 2011-06-01 DOI: 10.1101/lm.2111311

Elaine E Irvine, Laura Drinkwater, Kasia Radwanska, Hind Al-Qassab, Mark A Smith, Melissa O'Brien, Catherine Kielar, Agharul I Choudhury, Stefan Krauss, Jonathan D Cooper, Dominic J Withers, Karl Peter Giese

{"title":"Insulin receptor substrate 2 is a negative regulator of memory formation.","authors":"Elaine E Irvine, Laura Drinkwater, Kasia Radwanska, Hind Al-Qassab, Mark A Smith, Melissa O'Brien, Catherine Kielar, Agharul I Choudhury, Stefan Krauss, Jonathan D Cooper, Dominic J Withers, Karl Peter Giese","doi":"10.1101/lm.2111311","DOIUrl":"10.1101/lm.2111311","url":null,"abstract":"Insulin has been shown to impact on learning and memory in both humans and animals, but the downstream signaling mechanisms involved are poorly characterized. Insulin receptor substrate-2 (Irs2) is an adaptor protein that couples activation of insulin- and insulin-like growth factor-1 receptors to downstream signaling pathways. Here, we have deleted Irs2, either in the whole brain or selectively in the forebrain, using the nestin Cre- or D6 Cre-deleter mouse lines, respectively. We show that brain- and forebrain-specific Irs2 knockout mice have enhanced hippocampal spatial reference memory. Furthermore, NesCreIrs2KO mice have enhanced spatial working memory and contextual- and cued-fear memory. Deletion of Irs2 in the brain also increases PSD-95 expression and the density of dendritic spines in hippocampal area CA1, possibly reflecting an increase in the number of excitatory synapses per neuron in the hippocampus that can become activated during memory formation. This increase in activated excitatory synapses might underlie the improved hippocampal memory formation observed in NesCreIrs2KO mice. Overall, these results suggest that Irs2 acts as a negative regulator on memory formation by restricting dendritic spine generation.","PeriodicalId":520703,"journal":{"name":"Learning & memory (Cold Spring Harbor, N.Y.)","volume":" ","pages":"375-83"},"PeriodicalIF":0.0,"publicationDate":"2011-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371579/pdf/emss-62703.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40096428","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}

引用次数: 0