Abstract:
:MeCP2 is required both during postnatal neurodevelopment and throughout the adult life for brain function. Although it is well accepted that MeCP2 in the maturing nervous system is critical for establishing normal development, the functions of MeCP2 during adulthood are poorly understood. Particularly, the requirement of hippocampal MeCP2 for cognitive abilities in the adult is not studied. To characterize the role of MeCP2 in adult neuronal function and cognition, we used a temporal and region-specific disruption of MeCP2 expression in the hippocampus of adult male mice. We found that MeCP2 is required for long-term memory formation and that it controls the learning-induced transcriptional response of hippocampal neurons required for memory consolidation. Furthermore, we uncovered MeCP2 functions in the adult hippocampus that may underlie cognitive integrity. We showed that MeCP2 maintains the developmentally established chromatin configuration and epigenetic landscape of CA1 neurons throughout the adulthood, and that it regulates the expression of neuronal and immune-related genes in the adult hippocampus. Overall, our findings identify MeCP2 as a maintenance factor in the adult hippocampus that preserves signal responsiveness of the genome and allows for integrity of cognitive functions. This study provides new insight into how MeCP2 maintains adult brain functions, but also into the mechanisms underlying the cognitive impairments observed in RTT patients and highlights the understudied role of DNA methylation interpretation in adult cognitive processes.
journal_name
Neurobiol Learn Memjournal_title
Neurobiology of learning and memoryauthors
Gulmez Karaca K,Brito DVC,Zeuch B,Oliveira AMMdoi
10.1016/j.nlm.2018.02.010subject
Has Abstractpub_date
2018-03-01 00:00:00pages
84-97eissn
1074-7427issn
1095-9564pii
S1074-7427(18)30029-7journal_volume
149pub_type
杂志文章abstract::In the marine snail Hermissenda, associative learning can be accomplished by paired presentations of light and vestibular stimulation. It is generally assumed that associative learning depends upon the intensity or salience of the conditioned or unconditioned stimulus (CS and US, respectively). Accordingly, during Her...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1006/nlme.1999.3938
更新日期:2000-07-01 00:00:00
abstract::Stroke-induced cognitive impairments are of significant concern, however mechanisms that underpin these impairments remain poorly understood and researched. To further characterise cognitive impairments in our frontal cortex stroke model, and to align our assessments with what is used clinically, we tested young C57BL...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2020.107355
更新日期:2021-01-01 00:00:00
abstract::The amygdala, medial hypothalamus, dorsal periaqueductal gray (dPAG), superior and inferior colliculus together constitutes the encephalic aversion system which has been considered the main neural substrate for the integration of unconditioned aversive behavioral states. Within the amygdala the basolateral nucleus (BL...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2013.03.004
更新日期:2013-05-01 00:00:00
abstract::Renewal, or reinstatement, of responding to food cues after extinction may explain the inability to resist palatable foods and change maladaptive eating habits. Previously, we found sex differences in context-dependent renewal of extinguished Pavlovian conditioned responding to food cues. Context-induced renewal invol...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2016.12.004
更新日期:2017-03-01 00:00:00
abstract::We previously identified a set of 50 genes that were differentially transcribed in the hippocampal CA1 region of aged, learning-impaired rats compared to aged, superior learning animals during a Morris water maze paradigm. In the current study, we expressed three of these genes (Pctk1, Tcf12 and Ccnd1), which had show...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2011.09.006
更新日期:2012-01-01 00:00:00
abstract::Human episodic memory refers to the recollection of an unique past experience in terms of what happened, and where and when it happened. Factoring out the issue of conscious recollection, episodic memory, even at the behavioral level, has been difficult to demonstrate in non-human mammals. Although, it was previously ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2005.07.002
更新日期:2005-11-01 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::Numerous experiments using ex vivo electrophysiology suggest that mammalian learning and memory involves regulation of voltage-gated ion channels in terms of changes in function. Yet, little is known about learning-related regulation of voltage-gated ion channels in terms of changes in expression. In two experiments, ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2017.05.009
更新日期:2017-07-01 00:00:00
abstract::Evidence is reviewed that behavioral training and neural injury can engage metaplastic processes that regulate adaptive potential. This issue is explored within a model system that examines how training affects the capacity to learn within the lower (lumbosacral) spinal cord. Response-contingent (controllable) stimula...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2018.04.007
更新日期:2018-10-01 00:00:00
abstract::Non-selective inhibition of histone deacetylases (HDACs), enzymes that remove acetyl groups from histone core proteins, enhances cognition and NMDAR-dependent long-term potentiation at hippocampal CA3-CA1 synapses. It is not known whether this is a general mechanism by which HDACs modulate plasticity at other hippocam...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2014.06.008
更新日期:2014-10-01 00:00:00
abstract::When placed in a novel environment, mice tend to explore for a period of time, and then reduce the level of exploration. This reduction in locomotor or exploratory behavior is known as habituation and can occur within a single session or across sessions, respectively, termed intrasession and intersession habituation. ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2009.02.002
更新日期:2009-09-01 00:00:00
abstract::Testosterone (T) may enhance cognitive performance. However, its mechanisms are not well understood. First, we hypothesized that if T's effects are mediated in part through actions of its 5alpha-reduced metabolites, dihydrotestosterone (DHT) and/or 3alpha-androstanediol (3alpha-diol) in the hippocampus, then T, DHT, a...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2006.07.001
更新日期:2007-01-01 00:00:00
abstract::Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically releva...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章,评审
doi:10.1016/j.nlm.2013.11.014
更新日期:2014-09-01 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::Epidemiological studies demonstrated association between head injury (HI) and the subsequent development of Alzheimer's disease (AD). Certain hallmarks of AD, e.g. amyloid-β (Aβ) containing deposits, may be found in patients following traumatic BI (TBI). Recent studies uncover the cellular prion protein, PrP(C), as a ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2013.10.019
更新日期:2014-01-01 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::An increasing number of studies using human subjects substantiate the use of transcranial direct current stimulation (tDCS) as a noninvasive approach to treat various neurological symptoms. tDCS has been tested in conditions from motor to cognition dysfunctions. Performance enhancement of healthy subjects using tDCS h...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2019.107126
更新日期:2020-01-01 00:00:00
abstract::Down syndrome (DS) has an incidence of about 1/700 births, and is therefore the most common cause of cognitive and behavioral impairments in children. Recent studies on mouse models of DS indicate that a number of pharmacotherapies could be beneficial for restoring cognitive abilities in individuals with DS. Attention...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2014.10.002
更新日期:2014-12-01 00:00:00
abstract::Expression of immediate-early genes, like Egr-1, has been shown to be induced by activity-dependent synaptic plasticity or behavioral training and is widely thought to play an important role in long-term memory (LTM) formation. However, little is known about the role of Egr-1 in the maintenance of memory storage. Here...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2012.08.001
更新日期:2012-10-01 00:00:00
abstract::The hippocampus is important for memory and learning, being a brain site where initial memories are formed and where sharp wave - ripples (SWR) are found, which are responsible for mapping recent memories to long-term storage during sleep-related memory replay. While this conceptual schema is well established, specifi...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2018.04.018
更新日期:2019-04-01 00:00:00
abstract::Enriched environment (EE) has an important role in the development and plasticity of the brain. In this study, we investigated the maintenance of early EE exposure-induced changes of spatial sensitivity, and the possible underlying mechanisms of this maintenance. We found that, compared with the age-matched control, t...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2010.08.008
更新日期:2010-11-01 00:00:00
abstract::The study of bidirectional conditioning began more than a century ago, yet it has failed to take strong root in psychology and neuroscience. We revisit this topic by exploiting E. A. Asratyan's alternating procedure of stimulus presentation, in which both forward (e.g., A → B) and backward (e.g., B → A) training trial...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2020.107211
更新日期:2020-05-01 00:00:00
abstract::Heart rate (HR) conditioning in rabbits is a widely used model of classical conditioning of autonomic responding that is noted for being similar to the development of conditioned heart rate slowing (bradycardia) in humans. We have shown previously that in addition to HR changes to a tone conditioned stimulus (CS), the...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2012.12.011
更新日期:2013-02-01 00:00:00
abstract::Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and waterm...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2018.04.012
更新日期:2018-05-01 00:00:00
abstract::Aging is associated with cognitive decline, specifically in episodic memory. However, there are large individual differences in the extent of this decline and previous research suggests that these are associated with differences in executive functioning (EF). These EF differences, and associated differences in the enc...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2020.107251
更新日期:2020-09-01 00:00:00
abstract::We evaluated various forms of hippocampus-dependent learning and memory, and hippocampal synaptic plasticity in THY-Tau22 transgenic mice, a murine tauopathy model that expresses double-mutated 4-repeat human tau, and shows neuropathological tau hyperphosphorylation and aggregation throughout the brain. Focussing on h...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2010.12.005
更新日期:2011-03-01 00:00:00
abstract::In insects, cholinergic neurons are thought to transmit olfactory conditioned stimulus (CS) to the sites for associating the CS with unconditioned stimulus (US), but the types of acetylcholine (ACh) receptor used by neurons participating in the association have not been determined. In cockroaches, a type of nicotinic ...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2010.10.004
更新日期:2011-01-01 00:00:00
abstract::Sleep is involved in both the consolidation of discrete episodes, as well as the generalisation of acquired memories into schemata. Here, we have isolated early versus late periods of sleep in order to replicate previous behavioural findings and to demonstrate: i) that distinct sleep and sleep electroencephalography (...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2021.107384
更新日期:2021-01-15 00:00:00
abstract::Cocaine experience affects motivation structures such as the nucleus accumbens (NAc) and its major output target, the ventral pallidum (VP). Previous studies demonstrated that both NAc activity and hedonic responses change reliably as a taste cue comes to predict cocaine availability. Here we extended this investigati...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1016/j.nlm.2016.02.013
更新日期:2016-04-01 00:00:00
abstract::The present study examined the effects of posttraining ethanol administration upon retention of an appetitive task using a variety of retention behaviors associated with the task. Male C57BL/6J mice were individually trained to find a cheese pellet placed in the corner of an open field. Five behavioral measures were u...
journal_title:Neurobiology of learning and memory
pub_type: 杂志文章
doi:10.1006/nlme.2000.3960
更新日期:2001-01-01 00:00:00