remote memory [keywords]
- A prospective study of cerebral, frontal lobe, and temporal lobe volumes and neuropsychological performance in children with primary brain tumors treated with cranial radiation. [JOURNAL ARTICLE]
- Cancer 2016 Aug 29.
Cranial radiation therapy (RT) is an important component in the treatment of pediatric brain tumors. However, it can result in long-term effects on the developing brain. This prospective study assessed the effects of cranial RT on cerebral, frontal lobe, and temporal lobe volumes and their correlation with higher cognitive functioning.Ten pediatric patients with primary brain tumors treated with cranial RT and 14 age- and sex-matched healthy children serving as controls were evaluated. Quantitative magnetic resonance imaging and neuropsychological assessments (language, memory, auditory and visual processing, and vocabulary) were performed at the baseline and 6, 15, and 27 months after RT. The effects of age, the time since RT, and the cerebral RT dose on brain volumes and neuropsychological performance were analyzed with linear mixed effects model analyses.Cerebral volume increased significantly with age in both groups (P = .01); this increase in volume was more pronounced in younger children. Vocabulary performance was found to be significantly associated with a greater cerebral volume (P = .05) and a lower RT dose (P = .003). No relation was observed between the RT dose and the cerebral volume. There was no difference in the corresponding neuropsychological tests between the 2 groups.This prospective study found significant relations among the RT dose, cerebral volumes, and rate of vocabulary development among children receiving RT. The results of this study provide further support for clinical trials aimed at reducing cranial RT doses in the pediatric population. Cancer 2016. © 2016 American Cancer Society.
- Training a Constitutional Dynamic Network for Effector Recognition: Storage, Recall, and Erasing of Information. [JOURNAL ARTICLE]
- J Am Chem Soc 2016 Aug 29.
Constitutional dynamic libraries (CDLs) of hydrazones, acylhydrazones, and imines undergo reorganization and adaptation in response to chemical effectors (herein metal cations) via component exchange and selection. Such CDLs can be subjected to training by exposition to given effectors and keep memory of the information stored by interaction with a specific metal ion. The long-term storage of the acquired information into the set of constituents of the system allows for fast recognition on subsequent contacts with the same effector(s). Dynamic networks of constituents were designed to adapt orthogonally to different metal cations by up- and down-regulation of specific constituents in the final distribution. The memory may be erased by component exchange between the constituents so as to regenerate the initial (statistical) distribution. The libraries described represent constitutional dynamic systems capable of acting as information storage molecular devices, in which the presence of components linked by reversible covalent bonds in slow exchange and bearing adequate coordination sites allows for the adaptation to different metal ions by constitutional variation. The system thus performs information storage, recall, and erase processes.
- [Dissociating between Enhancing and Impairing Effects of Emotion on Cognition]. [JOURNAL ARTICLE, ENGLISH ABSTRACT]
- Sante Ment Que 2016; 41(1):15-34.
Objectives Emerging evidence suggests that emotion can have both enhancing and impairing effects on various cognitive processes. These opposing effects can be identified at different levels, both within the same cognitive process and across different processes, as well as at more general levels, such as in the case of the response to stress. The aim of the present review is to discuss recent advances in the mechanisms underlying the enhancing and impairing effects of emotion on different aspects within the same process (e.g., episodic memory) and across specific cognitive processes (perception vs. episodic memory, working memory vs. episodic memory), as well as in the context of the response to stress.Emerging Evidence The available evidence points to a number of aspects that dissociate the opposing effects of emotion on cognition. (i) Opposing effects within episodic memory can be attributed to different accounts, involving dissociation at different levels: central vs. peripheral trade-off, high vs. low prioritization of information processing, and items encoding vs. the formation of complex associations. (ii) The opposing effects across cognitive processes, such as perception and episodic memory, can be linked to dissociation between immediate/impairing vs. long-term/enhancing effects, which are mediated by common and dissociable neural mechanisms, involving bottom-up and top-down processes. (iii) Finally, in the larger context of the response to stress, emotional stress can lead to opposing effects depending on the degree, context, and controllability of the stressors.Conclusions Overall, the present review highlights the need to consider the various factors that can influence enhancing or impairing effects of emotion on cognition, in studies investigating emotion-cognition interactions. These issues are important for understanding mechanisms of emotion-cognition interactions not only in healthy functioning but also in emotional disturbances, where these opposing effects of emotion are exacerbated and deleterious.
- Photoperiodic Regulation of Cerebral Blood Flow in White-Footed Mice (Peromyscus leucopus). [Journal Article]
- eNeuro 2016 Jul-Aug; 3(4)
Individuals living outside the tropics need to adjust their behavioral and physiological repertoires throughout the year to adapt to the changing seasons. White-footed mice (Peromyscus leucopus) reduce hippocampal volumes, hippocampal-dependent memory function, long-term potentiation, and alter neurogenesis in response to short (winter-like) day lengths (photoperiods). During winter, these mice putatively shunt energy away from the brain to maximize peripheral thermogenesis, immune function, and survival. We hypothesized that these changes in brain function are accompanied by alterations in brain vasculature. We maintained white-footed mice in short (8 h light/16 h dark) or long (16 h light/8 h dark) photoperiods for 8-9 weeks. Mice were then perfused with fluorescein isothiocyanate (FITC)-conjugated tomato (Lycopersicon esculentum) lectin to visualize the perfused cerebrovasculature. Short-day mice reduced hippocampal and cortical capillary density (FITC(+) area); vessels isolated from short day-exposed mice expressed higher mRNA levels of the gelatinase matrix metalloproteinase 2 (MMP2). Additionally, short-day mice reduced cerebral blood flow ∼15% compared with their long-day counterparts, as assessed by laser speckle flowmetry. Immunohistochemistry revealed higher levels of MMP2 in the hippocampus of mice maintained in short days compared with long days, potentially contributing to the observed vascular remodeling. These data demonstrate that a discrete environmental signal (i.e., day length) can substantially alter cerebral blood flow in adult mammals.
- Endocannabinoids in brain plasticity: cortical maturation, HPA axis function and behavior. [REVIEW, JOURNAL ARTICLE]
- Brain Res 2016 Aug 25.
Marijuana use during adolescence has reached virtually every strata of society. The general population has the perception that marijuana use is safe for mature people and therefore is also safe for developing adolescents. However, both clinical and preclinical research shows that marijuana use, particularly prior to age 16, could have long-term effects on cognition, anxiety and stress-related behaviors, mood disorders and substance abuse. These effects derive from the role of the endocannabinoid system, the endogenous cannabinoid system, in the development of cortex, amygdala, hippocampus and hypothalamus during adolescence. Endocannabinoids are necessary for normal neuronal excitation and inhibition through actions at glutamate and GABA terminals. Synaptic pruning at excitatory synapses and sparing of inhibitory synapses likely results in changes in the balance of excitation/inhibition in individual neurons and within networks; processes which are necessary for normal cortical development. The interaction between prefrontal cortex (PFC), amygdala and hippocampus is responsible for emotional memory, anxiety-related behaviors and drug abuse and all utilize the endogenous cannabinoid system to maintain homeostasis. Also, endocannabinoids are required for fast and slow feedback in the normal stress response, processes which mature during adolescence. Therefore, exogenous cannabinoids, such as marijuana, have the potential to alter the course of development of each of these major systems (limbic, hypothalamic-pituitary-adrenal (HPA) axis and neocortex) if used during the critical period of brain development, adolescence.
- An energy-efficient intrinsic functional organization of human working memory: a resting-state functional connectivity study. [JOURNAL ARTICLE]
- Behav Brain Res 2016 Aug 25.
Working memory (WM) is the active maintenance of currently relevant information that was just experienced or retrieved from long-term memory but no longer exists in the external environment; however, the intrinsic functional organization of the brain underlying human WM performance remains largely unknown. We hypothesize that the intrinsic functional organization of human WM is an energy-efficient system. We tested this hypothesis by analyzing associations between WM performance (reaction times of correct responses) at different task difficulties (2-back and 3-back tasks) and the resting-state functional connectivity density (FCD) and strength (FCS) in 282 healthy young adults. Voxel-based FCD analysis showed that the reaction times were negatively correlated with the FCD values of several brain regions known to be engaged in WM performance: the right inferior parietal lobule and inferior frontal gyrus for both the 2-back and the 3-back tasks and the right superior parietal lobule, supramarginal gyrus, left inferior parietal lobule and bilateral middle occipital gyrus for the 3-back task. Further analyses showed that the FCS values of these regions with several frontal, parietal and occipital regions were also negatively correlated with the reaction times; the 3-back task was associated with much more functional connections than the 2-back task. These findings suggest that the intrinsic working memory network is an energy-efficient and hierarchical system. A simple working memory task is controlled only by the core subsystem; however, a complex working memory task is associated with more nodes and connections of the system.
- Persistent modifications of hippocampal synaptic function during remote spatial memory. [JOURNAL ARTICLE]
- Neurobiol Learn Mem 2016 Aug 25.
A widely accepted notion for a process underlying memory formation is that learning changes the efficacy of synapses by the mechanism of synaptic plasticity. While there is compelling evidence of changes in synaptic efficacy observed after learning, demonstration of persistent synaptic changes accompanying memory has been elusive. We report that acquisition of a hippocampus and long-term potentiation dependent memory for places persistently changes the function of CA1 synapses. Using extracellular recordings we measured CA3-CA1 and EC-CA1 synaptic responses and found robust changes in the CA3-CA1 pathway after memory training. Crucially, these changes in synaptic function lasted at least a month and coincided with the persistence of long-term place memories; the changes were only observed in animals that expressed robust memory, and not in animals with poor memory recall. Interestingly, our findings were observed at the level of populations of synapses; suggesting that memory formation recruits widespread synaptic circuits and persistently reorganizes their function to store information.
- Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation. [JOURNAL ARTICLE]
- Sleep 2016 Aug 19.
Sleep is important for consolidation of hippocampus-dependent memories. It is hypothesized that the temporal sequence of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep is critical for the weakening of nonadaptive memories and the subsequent transfer of memories temporarily stored in the hippocampus to more permanent memories in the neocortex. A great body of evidence supporting this hypothesis relies on behavioral, pharmacological, neural, and/or genetic manipulations that induce sleep deprivation or stage-specific sleep deprivation.We exploit an experimental model of circadian desynchrony in which intact animals are not deprived of any sleep stage but show fragmentation of REM and NREM sleep within nonfragmented sleep bouts. We test the hypothesis that the shortening of NREM and REM sleep durations posttraining will impair memory consolidation irrespective of total sleep duration.When circadian-desynchronized animals are trained in a hippocampus-dependent contextual fear-conditioning task they show normal short-term memory but impaired long-term memory consolidation. This impairment in memory consolidation is positively associated with the posttraining fragmentation of REM and NREM sleep but is not significantly associated with the fragmentation of total sleep or the total amount of delta activity. We also show that the sleep stage fragmentation resulting from circadian desynchrony has no effect on hippocampus-dependent spatial memory and no effect on hippocampus-independent cued fear-conditioning memory.Our findings in an intact animal model, in which sleep deprivation is not a confounding factor, support the hypothesis that the stereotypic sequence and duration of sleep stages play a specific role in long-term hippocampus-dependent fear memory consolidation.
- Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior. [JOURNAL ARTICLE]
- Curr Biol 2016 Aug 24.
Memories become labile and malleable to modification when recalled . Fear-conditioning experiments in both rodents and humans indicate that amygdala-localized short-term fear memories can be attenuated by disruption of their reconsolidation with extinction training soon after memory activation [2-7]. However, this may not be true for natural long-term fears. Studies in rodents indicate that although it is possible to disrupt the reconsolidation of older memories [8-11], they appear to be more resistant [1, 3, 9, 12, 13]. In humans, 1-week-old conditioned fear memories have been attenuated by behaviorally induced disruption of reconsolidation , but it remains to be seen whether this is possible for naturally occurring long-term fears and whether the underlying neural mechanisms are similar to those found in experimental fear-conditioning paradigms. Using functional brain imaging in individuals with a lifelong fear of spiders, we show that fear memory activation followed by repeated exposure to feared cues after 10 min, which disrupts reconsolidation, attenuates activity in the basolateral amygdala at re-exposure 24 hr later. In contrast, repeated exposure 6 hr after fear memory activation, which allows for reconsolidation, did not attenuate amygdala activity. Disrupted, but not undisrupted, reconsolidation facilitated approach behavior to feared cues, and approach behavior was inversely related to amygdala activity during re-exposure. We conclude that memory activation immediately preceding exposure attenuates the neural and behavioral expression of decades-old fear memories and that, similar to experimentally induced fear memories, the basolateral amygdala is crucially involved in this process.
- Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function. [JOURNAL ARTICLE]
- Cell Rep 2016 Aug 24.
Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/-) mice have enhanced long-term potentiation in the CA1 area of the hippocampus. In translationally oriented studies, we found that small-molecule HDAC inhibitors normalized hippocampal LTP and memory recall. A comprehensive set of next-generation sequencing experiments of hippocampal mRNA and methylated DNA isolated from Tcf4-deficient and WT mice before or shortly after experiential learning, with or without administration of vorinostat, identified "memory-associated" genes modulated by HDAC inhibition and dysregulated by Tcf4 haploinsufficiency. Finally, we observed that Hdac2 isoform-selective knockdown was sufficient to rescue memory deficits in Tcf4(+/-) mice.