- The Demise of the Synapse As the Locus of Memory: A Looming Paradigm Shift? [Journal Article]
- FSFront Syst Neurosci 2016; 10:88
- Synaptic plasticity is widely considered to be the neurobiological basis of learning and memory by neuroscientists and researchers in adjacent fields, though diverging opinions are increasingly being...
Synaptic plasticity is widely considered to be the neurobiological basis of learning and memory by neuroscientists and researchers in adjacent fields, though diverging opinions are increasingly being recognized. From the perspective of what we might call "classical cognitive science" it has always been understood that the mind/brain is to be considered a computational-representational system. Proponents of the information-processing approach to cognitive science have long been critical of connectionist or network approaches to (neuro-)cognitive architecture, pointing to the shortcomings of the associative psychology that underlies Hebbian learning as well as to the fact that synapses are practically unfit to implement symbols. Recent work on memory has been adding fuel to the fire and current findings in neuroscience now provide first tentative neurobiological evidence for the cognitive scientists' doubts about the synapse as the (sole) locus of memory in the brain. This paper briefly considers the history and appeal of synaptic plasticity as a memory mechanism, followed by a summary of the cognitive scientists' objections regarding these assertions. Next, a variety of tentative neuroscientific evidence that appears to substantiate questioning the idea of the synapse as the locus of memory is presented. On this basis, a novel way of thinking about the role of synaptic plasticity in learning and memory is proposed.
- The Association between Physical Activity During the Day and Long-Term Memory Stability. [Journal Article]
- SRSci Rep 2016 Dec 02; 6:38148
- Despite positive associations between chronic physical activity and memory; we have little understanding of how best to incorporate physical activity during the day to facilitate the consolidation of...
Despite positive associations between chronic physical activity and memory; we have little understanding of how best to incorporate physical activity during the day to facilitate the consolidation of information into memory, nor even how time spent physically active during the day relates to memory processes. The purpose of this investigation was to examine the relation between physical activity during the day and long-term memory. Ninety-two young adults learned a list of paired-associate items and were tested on the items after a 12-hour interval during which heart rate was recorded continuously. Although the percentage of time spent active during the day was unrelated to memory, two critical physical activity periods were identified as relating to the maintenance of long-term memory. Engaging in physical activity during the period 1 to 2-hours following the encoding of information was observed to be detrimental to the maintenance of information in long-term memory. In contrast, physical activity during the period 1-hour prior to memory retrieval was associated with superior memory performance, likely due to enhanced retrieval processing. These findings provide initial evidence to suggest that long-term memory may be enhanced by more carefully attending to the relative timing of physical activity incorporated during the day.
- MPP(+) inhibits mGluR1/5-mediated long-term depression in mouse hippocampus by calpain activation. [Journal Article]
- EJEur J Pharmacol 2016 Nov 28
- Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal sy...
Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP(+) incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses. Our further findings indicated that, this blockage was reversed by pre-application of calpain inhibitor III, but not by cathepsin inhibitors. Biochemical analysis showed that MPP(+) treatment stimulated calpain activation, displayed by spectrin breakdown. Interestingly, the level and activity of protein tyrosine phosphatase 1B (PTP1B) were reduced after MPP(+) incubation and the decrease of PTP1B was prohibited by calpain inhibitor III. In addition, PTP1B inhibitor also blocked DHPG-induced LTD, mimicking the effect of MPP(+). In summary, our data implicated that MPP(+) activated calpain-dependent PTP1B degradation, which subsequently impaired hippocampal LTD. This novel effect of MPP(+) might partially explain the impairment of memory processing in the pathogenesis of PD.
- The chemotherapeutic agent paclitaxel selectively impairs learning while sparing source memory and spatial memory. [Journal Article]
- BBBehav Brain Res 2016 Nov 28
- Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that hav...
Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task.
- Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviours in aged mice. [Journal Article]
- DNDev Neurobiol 2016 Dec 1
- The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular p...
The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here we show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviours. Using both Grhl3-knockout mice (Grhl3(-/-) ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3(flox/flox) ), we performed histological expression analyses and behavioural tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety and stress. We found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain, however aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviours suggestive of decreased fear and anxiety. We conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behaviour or hyperactivity. This article is protected by copyright. All rights reserved.
- ERP Correlates of Encoding Success and Encoding Selectivity in Attention Switching. [Journal Article]
- PlosPLoS One 2016; 11(12):e0167396
- Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (...
Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures-memory selectivity and global memory-to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm-in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials-with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable.
- Long-term persistence of immunity after hepatitis B vaccination: A fact not a fancy. [Journal Article]
- HVHum Vaccin Immunother 2016 Dec 1; :0
- On the basis of an article previously published in the journal regarding immune persistence after hepatitis B vaccination in infancy, I discuss why this persistence is a fact and not a fancy. Immune ...
On the basis of an article previously published in the journal regarding immune persistence after hepatitis B vaccination in infancy, I discuss why this persistence is a fact and not a fancy. Immune memory after a primary vaccination series has been widely demonstrated by prompt response to booster doses and the proliferation of T cells secreting IFNγ. In a large cohort of medical students, 79% of subjects were positive for anti-HBs antibodies, and only 1.9% of the subjects had serological evidence of past hepatitis B infection. To prevent severe diseases, such as hepatitis B, it is very important that the majority of the population is vaccinated, especially those employed in health care, as vaccination is the most effective weapon to hepatitis B, which is still widespread worldwide.
- Rumination and self-reflection in stress narratives and relations to psychological functioning. [Journal Article]
- MMemory 2017; 25(1):44-56
- The longitudinal study aims to expand what is known about the costs and benefits of narrating stressful experiences by exploring changes in rumination within the narrative process and comparing it to...
The longitudinal study aims to expand what is known about the costs and benefits of narrating stressful experiences by exploring changes in rumination within the narrative process and comparing it to changes in self-reflection. Rumination (e.g., brooding, self-criticism, and negative emotions) and self-reflection were measured in stress narratives of 56 college students. There were several goals: (1) examine changes in narrative rumination and narrative self-reflection over 3 days of writing, (2) examine the relations among the changes in narrative rumination variables and narrative self-reflection and (3) examine how changes in narrative rumination and narrative self-reflection relate to multiple measures of psychological functioning. Overall, individuals increased self-reflection over the 3-day writing task. Individuals who increased ruminative brooding across the 3 days of writing showed lower ego identity development (short term and long term) and self-esteem (short term), while increased self-criticism was positively correlated with identity distress (short term). Implications of the different aspects of narrative rumination, specifically in the context of stressful experiences, are discussed.
- A neural model of normal and abnormal learning and memory consolidation: adaptively timed conditioning, hippocampus, amnesia, neurotrophins, and consciousness. [Journal Article]
- CACogn Affect Behav Neurosci 2016 Nov 30
- How do the hippocampus and amygdala interact with thalamocortical systems to regulate cognitive and cognitive-emotional learning? Why do lesions of thalamus, amygdala, hippocampus, and cortex have di...
How do the hippocampus and amygdala interact with thalamocortical systems to regulate cognitive and cognitive-emotional learning? Why do lesions of thalamus, amygdala, hippocampus, and cortex have differential effects depending on the phase of learning when they occur? In particular, why is the hippocampus typically needed for trace conditioning, but not delay conditioning, and what do the exceptions reveal? Why do amygdala lesions made before or immediately after training decelerate conditioning while those made later do not? Why do thalamic or sensory cortical lesions degrade trace conditioning more than delay conditioning? Why do hippocampal lesions during trace conditioning experiments degrade recent but not temporally remote learning? Why do orbitofrontal cortical lesions degrade temporally remote but not recent or post-lesion learning? How is temporally graded amnesia caused by ablation of prefrontal cortex after memory consolidation? How are attention and consciousness linked during conditioning? How do neurotrophins, notably brain-derived neurotrophic factor (BDNF), influence memory formation and consolidation? Is there a common output path for learned performance? A neural model proposes a unified answer to these questions that overcome problems of alternative memory models.
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- Memory Transformation Enhances Reinforcement Learning in Dynamic Environments. [Journal Article]
- JNJ Neurosci 2016 Nov 30; 36(48):12228-12242
- Over the course of systems consolidation, there is a switch from a reliance on detailed episodic memories to generalized schematic memories. This switch is sometimes referred to as "memory transforma...
Over the course of systems consolidation, there is a switch from a reliance on detailed episodic memories to generalized schematic memories. This switch is sometimes referred to as "memory transformation." Here we demonstrate a previously unappreciated benefit of memory transformation, namely, its ability to enhance reinforcement learning in a dynamic environment. We developed a neural network that is trained to find rewards in a foraging task where reward locations are continuously changing. The network can use memories for specific locations (episodic memories) and statistical patterns of locations (schematic memories) to guide its search. We find that switching from an episodic to a schematic strategy over time leads to enhanced performance due to the tendency for the reward location to be highly correlated with itself in the short-term, but regress to a stable distribution in the long-term. We also show that the statistics of the environment determine the optimal utilization of both types of memory. Our work recasts the theoretical question of why memory transformation occurs, shifting the focus from the avoidance of memory interference toward the enhancement of reinforcement learning across multiple timescales.