Abstract:
:Intellectual disability is a common feature in genetic disorders with enhanced RAS-ERK1/2 signaling, including neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). Additional training trials and additional spacing between trials, respectively, restores memory deficits in animal models of NF1 and NS. However, the relationship between the underlying mechanisms in these strategies remain obscure. Here, we developed an approach to examine the effect of adding training trials or spacing to a weak training protocol and used genetic and behavioral manipulations in Drosophila to explore such question. We found that repetition and spacing effects are highly related, being equally effective to improve memory in control flies and sharing mechanistic bases, including the requirement of RAS activity in mushroom body neurons and protein synthesis dependence. After spacing or repeating learning trials, memory improvement depends on the formation of long-term memory (LTM). Moreover, a disease-related gain-of-function RasV152G allele impaired LTM. Using minimal training protocols, we established that both learning strategies were also equally effective for memory rescue in the RasV152G mutant and showed non-additive interaction of the spacing and repetition effects. Memory improvement was never detected after Ras inhibition. We conclude that memory improvement by spacing or repeating training trials are two ways of using the same molecular resources, including RAS-ERK1/2-dependent signaling. This evidence supports the concept that learning problems in RAS-related disorders depend on the impaired ability to exploit the repetition and the spacing effect required for long-term memory induction.
journal_name
Neurobiol Learn Memjournal_title
Neurobiology of learning and memoryauthors
Cattaneo V,San Martin A,Lew SE,Gelb BD,Pagani MRdoi
10.1016/j.nlm.2020.107233subject
Has Abstractpub_date
2020-07-01 00:00:00pages
107233eissn
1074-7427issn
1095-9564pii
S1074-7427(20)30077-0journal_volume
172pub_type
杂志文章abstract::Environmental stimuli during neonatal periods play an important role in the development of cognitive function. In this study, we examined the long-term effects of neonatal tactile stimulation (TS) on spatial working memory (SWM) and related mechanisms. We also investigated whether TS-induced effects could be counterac...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2007.10.010
更新日期:2008-05-01 00:00:00
abstract::Recent models of hippocampal function have emphasized its role in relational binding - the ability to form lasting representations regarding the relations among distinct elements or items which can support memory performance, even over brief delays (e.g., several seconds). The present study examined the extent to whic...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2015.11.017
更新日期:2016-10-01 00:00:00
abstract::Sleep loss affects emotional memory, but the specific effects on its contextual and non-contextual aspects are unknown. In this study we investigated the possible differential influence of one night of sleep deprivation on the encoding and subsequent recall of these two aspects of emotional information. Forty-eight he...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2016.03.007
更新日期:2016-05-01 00:00:00
abstract::Activity dependent calcium entry into neurons can initiate a form of synaptic plasticity called long-term potentiation (LTP). This phenomenon is considered by many to be one possible cellular mechanism underlying learning and memory. The calcium entry that induces this phenomenon can occur when N-methyl-D-aspartate re...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2003.10.003
更新日期:2004-03-01 00:00:00
abstract::Pre-verbal infants and non-human animals associate small numbers with the left space and large numbers with the right space. Birds and primates, trained to identify a given position in a sagittal series of identical positions, whenever required to respond on a left/right oriented series, referred the given position st...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2016.05.010
更新日期:2016-09-01 00:00:00
abstract::Performing sequences of movements is a ubiquitous skill that involves dopamine transmission. However, it is unclear which components of the dopamine system contribute to which aspects of motor sequence learning. Here we used a genetic approach to investigate the relationship between different components of the dopamin...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2015.09.009
更新日期:2015-11-01 00:00:00
abstract::Differences in cytoarchitectural organization and connectivity distinguishes granular (or area 29, A29) and dysgranular (or area 30, A30) subdivisions of the retrosplenial cortex (RSC). Although increasing evidence supports the participation of RSC in contextual fear learning and memory, the contribution of each RSC s...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2020.107229
更新日期:2020-05-01 00:00:00
abstract::Trace eyeblink conditioning requires animals to associate a neutral stimulus (CS) and an aversive periorbital shock (US) that occurred moment later. Acquisition in this conditioning depends on several forebrain regions including the hippocampus, medial prefrontal, and entorhinal cortices in addition to the cerebellum....
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2012.12.014
更新日期:2013-02-01 00:00:00
abstract::Sleep facilitates declarative memory processing. However, we know little about whether sleep plays a role in the processing of a fundamental feature of declarative memory, relational memory - the flexible representation of items not directly learned prior to sleep. Thirty-one healthy participants first learned at 12 p...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.nlm.2010.02.003
更新日期:2010-05-01 00:00:00
abstract::It is well established that neurons are plastic and can change the strength of their connections with other neurons depending on their recent history. While many molecular entities involved in plastic processes were already described, the role of a store-operated calcium channel ORAI1 in neuronal plasticity is not kno...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2016.12.024
更新日期:2017-04-01 00:00:00
abstract::Exposure to acute, inescapable stress produces a facilitation of subsequent classical eyeblink conditioning in male rats. The same stress exposure produces a profound deficit in classical eyeblink conditioning in females. Activation of N-methyl-d-aspartate receptors (NMDAr) is necessary for the effect of stress on lea...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2009.08.002
更新日期:2010-01-01 00:00:00
abstract::Traditional learning theory has developed models that can accurately predict and describe the course of learned behavior. These "psychological process" models rely on hypothetical constructs that are usually thought to be not directly measurable or manipulable. Recently, and mostly in parallel, the neural mechanisms u...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2013.10.021
更新日期:2014-02-01 00:00:00
abstract::This study was designed to examine the effect of corticosterone on consolidation of contextual fear memory and hippocampal long-term potentiation (LTP) in rats. In Experiment 1, dose-response effects of corticosterone on consolidation of contextual fear memory were determined. Immediately after training in contextual ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2008.10.008
更新日期:2009-03-01 00:00:00
abstract::Although social, physical, and cognitive activities have each been suggested to reduce the risk of Alzheimer's disease (AD), epidemiologic studies cannot determine which activity or combination of activities is most important. To address this question, mutant APP transgenic AD mice were reared long-term in one of four...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2007.07.007
更新日期:2007-10-01 00:00:00
abstract::The therapeutic efficacy of the synthetic β-adrenergic receptor blocker, propranolol, for the treatment of post-traumatic stress disorder (PTSD) is currently being debated. Mixed results have been published regarding propranolol's ability to disrupt the consolidation and reconsolidation of memories. Here, we use the i...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2018.01.010
更新日期:2018-03-01 00:00:00
abstract::Drug abuse, overeating, and smoking are all examples of instrumental behaviors that often involve chains or sequences of behavior. A behavior chain is minimally composed of a procurement response that is required in order for a subsequent consumption response to be reinforced. Despite the translational importance of b...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章,评审
doi:10.1016/j.nlm.2016.06.005
更新日期:2016-09-01 00:00:00
abstract::Temporal lobe epilepsy patients have demonstrated a relative preservation in the integrity of implicit memory procedures. We examined performance in a verbal implicit and explicit memory task in left anterior temporal lobectomy patients (LATL) and healthy normal controls (NCs) while undergoing fMRI. We hypothesized th...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2012.08.005
更新日期:2012-10-01 00:00:00
abstract::Adult male Wistar rats with a substantia nigra pars compacta (SNc) lesion induced by intranigral administration of 1 micromol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used as a model of early phase Parkinson's disease (PD). This lesion caused a partial depletion of striatal dopamine (DA). The animals w...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2004.06.006
更新日期:2004-09-01 00:00:00
abstract::Human drug addiction is a complex disorder, in which exogenous substances are able to recruit and maintain behaviors involved in drug taking. Many drugs that are addictive in humans are able to act on natural brain systems for learning and memory, and while many memory systems may be affected by addictive drugs, work ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2014.11.007
更新日期:2015-02-01 00:00:00
abstract::It has recently become widely appreciated that value-based decision making is supported by multiple computational strategies. In particular, animal and human behavior in learning tasks appears to include habitual responses described by prominent model-free reinforcement learning (RL) theories, but also more deliberati...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2014.04.014
更新日期:2015-01-01 00:00:00
abstract::This experiment tests the hypothesis that the cholinergic nucleus basalis magnocellularis (NBM) is necessary for complex or configural association learning, but not elemental or simple association learning. Male Long-Evans rats with bilateral 192 IgG-saporin lesions of the NBM (n = 12) and sham-operated controls (n = ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1006/nlme.2001.4013
更新日期:2002-03-01 00:00:00
abstract::Pre-test exposure to training-related cues is known to improve subsequent retention performance. To identify brain regions engaged in processes promoted by retrieval cues, a brain imaging approach using the [6-14C]glucose autoradiographic technique was used. Sprague-Dawley rats trained in a brightness discrimination a...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/s1074-7427(02)00010-2
更新日期:2003-01-01 00:00:00
abstract::Glucocorticoid receptor activation within the basolateral amygdala (BLA) during fear conditioning may mediate enhancement in rats chronically exposed to stress levels of corticosterone. Male Sprague-Dawley rats received corticosterone (400 microg/ml) in their drinking water (days 1-21), a manipulation that was previou...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2004.01.002
更新日期:2004-05-01 00:00:00
abstract::It is widely accepted that unitization can promote familiarity-based associative recognition, but the role of unitization in recognition of individual component elements which originate from compound words remains unclear. The goals of this study were to elaborate on how unitization affects item recognition and furthe...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2019.107130
更新日期:2020-01-01 00:00:00
abstract::N-methyl-D-aspartate receptors (NMDARs) are critically involved in various learning mechanisms including modulation of fear memory, brain development and brain disorders. While NMDARs mediate opposite effects on medial prefrontal cortex (mPFC) interneurons and excitatory neurons, NMDAR antagonists trigger profound cor...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2014.12.012
更新日期:2015-03-01 00:00:00
abstract::We developed a single-trial cue-location memory task in which rats experienced an auditory cue while exploring an environment. They then recalled and avoided the sound origination point after the cue was paired with shock in a separate context. Subjects with medial prefrontal cortical (mPFC) lesions made no such avoid...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2009.09.003
更新日期:2010-01-01 00:00:00
abstract::The effects of morphine (6.3, 12.6, and 25.2 mg/kg) on active avoidance behavior of BALB/C mice are explored in three acquisition sessions and in two subsequent performance sessions. Morphine-treated animals showed an increase in avoidance acquisition with respect to control group without differences in performance. H...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1006/nlme.1997.3804
更新日期:1998-03-01 00:00:00
abstract::Mixed results with the synthetic β-adrenergic receptor blocker, propranolol, have been reported in human populations with regards to its therapeutic efficacy for PTSD treatments targeting the memory reconsolidation process. Stress alters the ability to form and maintain memory, but whether the causal neuronal mechanis...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2016.09.013
更新日期:2016-12-01 00:00:00
abstract::Previous studies have reported that drugs affecting neuromodulatory systems within the basolateral amygdala (BLA), including drugs affecting muscarinic cholinergic receptors, modulate the consolidation of many kinds of training, including contextual fear conditioning (CFC). The present experiments investigated the inv...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2008.07.012
更新日期:2009-01-01 00:00:00
abstract::Human studies of sleep and cognition have established thatdifferent sleep stages contribute to distinct aspects of cognitive and emotional processing. However, since the majority of these findings are based on single-night studies, it is difficult to determine whether such effects arise due to individual, between-subj...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2016.07.032
更新日期:2016-10-01 00:00:00