22 research outputs found

    Pyramid Exploration Intervention, Environmental Enrichment, Aerobic Swimming Exercise and Brain Neuroplasticity in the Kainate Rat Model of Temporal Lobe Epilepsy

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    Previous studies have shown that environmental enrichment increases neurogenesis and reverses learning and memory deficits in rats with kainate-induced seizures. We tested the hypothesis that exploring a wooden pyramid for 3h/d augments neurogenesis and attenuates the learning and memory deficits following chemical lesioning of the hippocampus and motor cortex with kainic acid (KA). A pyramid exploration intervention (PEI) was created by subjecting rats to residing in a pyramidal wooden structure of 3 h/d for 30 d. We also compared the effects on neurogenesis for PEI to those for aerobic (swimming) exercise (EX) and environmental enrichment via exploration of a rectangular-shaped wooden cage. Following KA seizures, the PEI increased brain neurogenesis. Differences in measures of neurogenesis were not significantly different than those for EX and EE. Aerobic (swimming) exercise and novel environment exposures appear to increase neural plasticity and may be considered a complementary treatment for epilepsy

    Norepinephrine Triggers Metaplasticity of LTP by Increasing Translation of Specific mRNAs

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    Norepinephrine (NE) is a key modulator of synaptic plasticity in the hippocampus, a brain structure crucially involved in memory formation. NE boosts synaptic plasticity mostly through initiation of signaling cascades downstream from beta (β)-adrenergic receptors (β-ARs). Previous studies demonstrated that a β-adrenergic receptor agonist, isoproterenol, can modify the threshold for long-term potentiation (LTP), a putative cellular mechanism for learning and memory, in a process known as “metaplasticity.” Metaplasticity is the ability of synaptic plasticity to be modified by prior experience. We asked whether NE itself could engage metaplastic mechanisms in area CA1 of mouse hippocampal slices. Using extracellular field potential recording and stimulation, we show that application of NE (10 µM), which did not alter basal synaptic strength, enhances the future maintenance of LTP elicited by subthreshold, high-frequency stimulation (HFS: 1 × 100 Hz, 1 sec). HFS applied 30 min after NE washout induced long-lasting (>4 h) LTP, which was significantly extended in duration relative to HFS alone. This NE-induced metaplasticity required β1-AR activation, as coapplication of the β1-receptor antagonist CGP-20712A (1 µM) attenuated maintenance of LTP. We also found that NE-mediated metaplasticity was translation- and transcription-dependent. Polysomal profiles of CA1 revealed increased translation rates for specific mRNAs during NE-induced metaplasticity. Thus, activation of β-ARs by NE primes synapses for future long-lasting plasticity on time scales extending beyond fast synaptic transmission; this may facilitate neural information processing and the subsequent formation of lasting memories

    Founder Effect: Breeding a Dog for the Elderly Gentleman Reveals an Animal Model of a Human Genetic Disorder

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    Animal models of genetic disorders that have risen due to selective breeding can be used as a valuable model to teach the basic concepts of population genetics. The Clumber Spaniel is a breed of dog created in the mid-1700s by the 4th Duc du Noailles. He selectively bred this dog for the elderly gentleman. This sleepy-looking breed survives today, though 1% suffer from severe exercise intolerance due to an autosomal-recessive founder mutation in the pyruvate dehydrogenase phosphatase 1 (PDP1) gene. PDP1 deficiency was long suspected to be a human metabolic disorder and described at the molecular level in 2005 by Robinson and coworkers. The Robinson group later identified a founder mutation within the PDP1 gene of the Clumber spaniel. This case clearly illustrates how a detrimental mutant allele in a small population, when selecting for phenotype, can persist in the progeny of that group. In this review, we discuss the origin of the “Founder Effect” theory and present an example of how a bottleneck that occurred during the selective breeding of the Clumber spaniel over 250 years ago led to the current genetic status of the breed. Today, genotyping can help reduce the incidence of PDP1 in the Clumber breed

    Norepinephrine, beyond the Synapse: Coordinating Epigenetic Codes for Memory

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    The noradrenergic system is implicated in neuropathologies contributing to major disorders of the memory, including post-traumatic stress disorder and Alzheimer’s disease. Determining the impact of norepinephrine on cellular function and plasticity is thus essential for making inroads into our understanding of these brain conditions, while expanding our capacity for treating them. Norepinephrine is a neuromodulator within the mammalian central nervous system which plays important roles in cognition and associated synaptic plasticity. Specifically, norepinephrine regulates the formation of memory through the stimulation of β-ARs, increasing the dynamic range of synaptic modifiability. The mechanisms through which NE influences neural circuit function have been extended to the level of the epigenome. This review focuses on recent insights into how the noradrenergic recruitment of epigenetic modifications, including DNA methylation and post-translational modification of histones, contribute to homo- and heterosynaptic plasticity. These advances will be placed in the context of synaptic changes associated with memory formation and linked to brain disorders and neurotherapeutic applications

    Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer’s Disease

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    Epigenetic mechanisms, which include DNA methylation, a variety of post-translational modifications of histone proteins (acetylation, phosphorylation, methylation, ubiquitination, sumoylation, serotonylation, dopaminylation), chromatin remodeling enzymes, and long non-coding RNAs, are robust regulators of activity-dependent changes in gene transcription. In the brain, many of these epigenetic modifications have been widely implicated in synaptic plasticity and memory formation. Dysregulation of epigenetic mechanisms has been reported in the aged brain and is associated with or contributes to memory decline across the lifespan. Furthermore, alterations in the epigenome have been reported in neurodegenerative disorders, including Alzheimer’s disease. Here, we review the diverse types of epigenetic modifications and their role in activity- and learning-dependent synaptic plasticity. We then discuss how these mechanisms become dysregulated across the lifespan and contribute to memory loss with age and in Alzheimer’s disease. Collectively, the evidence reviewed here strongly supports a role for diverse epigenetic mechanisms in memory formation, aging, and neurodegeneration in the brain

    Low voltage powering of on-detector electronics for HL-LHC experiments upgrades

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    All LHC experiments will be upgraded during the next LHC long shutdowns (LS2 and LS3). The increase in resolution and luminosity and the use of more advanced CMOS technology nodes typically implies higher current consumption of the on-detector electronics. In this context, and in view of limiting the cable voltage drop, point-of-load DC-DC converters will be used on detector. This will have a direct impact on the existing powering scheme, implying new AC-DC and/or DC-DC stages as well as changes in the power cabling infrastructure. This paper presents the first results obtained while evaluating different LV powering schemes and distribution layouts for HL-LHC trackers. The precise low voltage power source requirements are being assessed and understood using the CMS tracker upgrade as a use-case

    Associations of Alpha and Beta Interhemispheric EEG Coherences with Indices of Attentional Control and Academic Performance

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    Introduction. Heretofore, research on optimizing academic performance has suffered from an inability to translate what is known about an individual\u27s learning behaviors to how effectively they are able to use the critical nodes and hubs in their cerebral cortex for learning. A previous study from our laboratory suggests that lower theta-beta ratios (TBRs) measured by EEG may be associated with higher academic performance in a medical school curriculum. Methods. In this study, we tested the hypothesis that TBR and academic performance may be correlated with EEG coherence, a measure of brain connectivity. We analyzed the interhemispheric coherences of the subjects involved in our prior study. TBR and coherence measurements were made at 19 scalp electrode recording sites and 171 electrode combinations with eyes open and closed (EO, EC). Control data were acquired during a session of acclimation to the research protocol 3 d before an initial examination in anatomy-physiology (control exam) and were repeated five weeks later, 3 d before a second exam covering different anatomy-physiology topics (comparison exam). Results. Between the control and comparison exams, beta coherences increased significantly at the frontal pole, frontal, parietal, midtemporal, posterior temporal, and occipital recording sites under the EO condition and at the inferior frontal, central, midtemporal, and posterior temporal sites under the EC condition. Alpha coherences increased significantly at the same sites and under the same EO/EC conditions as found for the beta coherences. The beta coherences were negatively correlated with the TBR and were positively correlated with the comparison exam score at the midfrontal electrode site (F3-F4) but only under the EO condition. Beta and alpha coherences at the midfrontal, inferior frontal midtemporal, posterior temporal, and occipital sites were also negatively correlated with the average TBR under the EO condition. Conclusions. Lower TBR, an indicator of attentional control, was associated with higher alpha and beta interhemispheric coherences measured with eyes open at sites overlying the frontal, temporal, and occipital cortices. Changes in EEG coherences and TBRs might be useful as neurophysiological measures of neuroplasticity and the efficacy of strategies for preventing academic underachievement and treatments for improving academic performance
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