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Different protocols of physical exercise produce different effects on synaptic and structural proteins in motor areas of the rat brain

Garcia, Priscila C.; Real, Caroline C.; Ferreira, Ana F. B.; Alouche, Sandra R.; Britto, Luiz R. G.; Pires, Raquel S.
Fonte: ELSEVIER SCIENCE BV; AMSTERDAM Publicador: ELSEVIER SCIENCE BV; AMSTERDAM
Tipo: Artigo de Revista Científica
Português
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474.18145%
The plastic brain responses generated by the training with acrobatic exercise (AE) and with treadmill exercise (TE) may be different. We evaluated the protein expression of synapsin I (SYS), synaptophysin (SYP), microtubule-associated protein 2 (MAP2) and neurofilaments (NF) by immunohistochemistry and Western blotting in the motor cortex, striatum and cerebellum of rats subjected to TE and AE. Young adult male Wistar rats were divided into 3 groups: sedentary (Sed) (n=15), TE (n=20) and AE (n=20). The rats were trained 3 days/week for 4 weeks on a treadmill at 0.6 km/h, 40 min/day (TE), or moved through a circuit of obstacles 5 times/day (AE). The rats from the TE group exhibited a significant increase of SYS and SYP in the motor cortex, of NF68, SYS and SYP in the striatum, and of MAP2, NF and SYS in the cerebellum, whereas NF was decreased in the motor cortex and the molecular layer of the cerebellar cortex. On the other hand, the rats from the AE group showed a significant increase of MAP2 and SYP in the motor cortex, of all four proteins in the striatum, and of SYS in the cerebellum. In conclusion, AE induced changes in the expression of synaptic and structural proteins mainly in the motor cortex and striatum, which may underlie part of the learning of complex motor tasks. TE...

Plasticity of resting state brain networks in recovery from stress

Marques, Fernanda; Palha, Joana Almeida; Cerqueira, João; Soares, José Miguel; Sousa, Nuno; Santos, Nadine Correia; Marques, Paulo César Gonçalves; Sampaio, Adriana; Ferreira, Luís Miguel
Fonte: Frontiers Research Foundation Publicador: Frontiers Research Foundation
Tipo: Artigo de Revista Científica
Publicado em /12/2013 Português
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479.73277%
Chronic stress has been widely reported to have deleterious impact in multiple biological systems. Specifically, structural and functional remodeling of several brain regions following prolonged stress exposure have been described; importantly, some of these changes are eventually reversible. Recently, we showed the impact of stress on resting state networks (RSNs), but nothing is known about the plasticity of RSNs after recovery from stress. Herein, we examined the "plasticity" of RSNs, both at functional and structural levels, by comparing the same individuals before and after recovery from the exposure to chronic stress; results were also contrasted with a control group. Here we show that the stressed individuals after recovery displayed a decreased resting functional connectivity in the default mode network (DMN), ventral attention network (VAN), and sensorimotor network (SMN) when compared to themselves immediately after stress; however, this functional plastic recovery was only partial as when compared with the control group, as there were still areas of increased connectivity in dorsal attention network (DAN), SMN and primary visual network (VN) in participants recovered from stress. Data also shows that participants after recovery from stress displayed increased deactivations in DMN...

COORDINATION OF SIZE AND NUMBER OF EXCITATORY AND INHIBITORY SYNAPSES RESULTS IN A BALANCED STRUCTURAL PLASTICITY ALONG MATURE HIPPOCAMPAL CA1 DENDRITES DURING LTP

Bourne, Jennifer N.; Harris, Kristen M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/2011 Português
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486.1308%
Enlargement of dendritic spines and synapses correlates with enhanced synaptic strength during long-term potentiation (LTP), especially in immature hippocampal neurons. Less clear is the nature of this structural synaptic plasticity on mature hippocampal neurons, and nothing is known about the structural plasticity of inhibitory synapses during LTP. Here the timing and extent of structural synaptic plasticity and changes in local protein synthesis evidenced by polyribosomes were systematically evaluated at both excitatory and inhibitory synapses on CA1 dendrites from mature rats following induction of LTP with theta-burst stimulation (TBS). Recent work suggests dendritic segments can act as functional units of plasticity. To test whether structural synaptic plasticity is similarly coordinated, we reconstructed from serial section transmission electron microscopy all of the spines and synapses along representative dendritic segments receiving control stimulation or TBS-LTP. At 5 min after TBS, polyribosomes were elevated in large spines suggesting an initial burst of local protein synthesis, and by 2 hr only those spines with further enlarged synapses contained polyribosomes. Rapid induction of synaptogenesis was evidenced by an elevation in asymmetric shaft synapses and stubby spines at 5 min and more nonsynaptic filopodia at 30 min. By 2 hr...

The structural plasticity of Tom71 for mitochondrial precursor translocations

Li, Jingzhi; Cui, Wenjun; Sha, Bingdong
Fonte: International Union of Crystallography Publicador: International Union of Crystallography
Tipo: Artigo de Revista Científica
Publicado em 21/08/2010 Português
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574.18145%
Tom70 family members may exhibit structural plasticity when complexed with Hsp70/Hsp90. This structural plasticity enables Tom70 to accommodate various precursor substrates for mitochondrial translocation.

Structural Plasticity and Hippocampal Function

Leuner, Benedetta; Gould, Elizabeth
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
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475.6891%
The hippocampus is a region of the mammalian brain that shows an impressive capacity for structural reorganization. Preexisting neural circuits undergo modifications in dendritic complexity and synapse number, and entirely novel neural connections are formed through the process of neurogenesis. These types of structural change were once thought to be restricted to development. However, it is now generally accepted that the hippocampus remains structurally plastic throughout life. This article reviews structural plasticity in the hippocampus over the lifespan, including how it is investigated experimentally. The modulation of structural plasticity by various experiential factors as well as the possible role it may have in hippocampal functions such as learning and memory, anxiety, and stress regulation are also considered. Although significant progress has been made in many of these areas, we highlight some of the outstanding issues that remain.

High Affinity Antigen Recognition of the Dual Specific Variants of Herceptin Is Entropy-Driven in Spite of Structural Plasticity

Bostrom, Jenny; Haber, Lauric; Koenig, Patrick; Kelley, Robert F.; Fuh, Germaine
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 22/04/2011 Português
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The antigen-binding site of Herceptin, an anti-human Epidermal Growth Factor Receptor 2 (HER2) antibody, was engineered to add a second specificity toward Vascular Endothelial Growth Factor (VEGF) to create a high affinity two-in-one antibody bH1. Crystal structures of bH1 in complex with either antigen showed that, in comparison to Herceptin, this antibody exhibited greater conformational variability, also called “structural plasticity”. Here, we analyzed the biophysical and thermodynamic properties of the dual specific variants of Herceptin to understand how a single antibody binds two unrelated protein antigens. We showed that while bH1 and the affinity-improved bH1-44, in particular, maintained many properties of Herceptin including binding affinity, kinetics and the use of residues for antigen recognition, they differed in the binding thermodynamics. The interactions of bH1 and its variants with both antigens were characterized by large favorable entropy changes whereas the Herceptin/HER2 interaction involved a large favorable enthalpy change. By dissecting the total entropy change and the energy barrier for dual interaction, we determined that the significant structural plasticity of the bH1 antibodies demanded by the dual specificity did not translate into the expected increase of entropic penalty relative to Herceptin. Clearly...

Signalling pathways underlying structural plasticity of dendritic spines

Patterson, Michael; Yasuda, Ryohei
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em /08/2011 Português
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485.04188%
Synaptic plasticity, or changes in synaptic strength, is thought to underlie learning and memory. Imaging studies, mainly in brain slices, have revealed that long-term synaptic plasticity of excitatory synapses in hippocampal neurons is coupled with structural plasticity of dendritic spines, which is thought to be essential for inducing and regulating functional plasticity. Using pharmacological and genetic manipulation, the signalling network underlying structural plasticity has been extensively studied. Furthermore, the recent advent of fluorescence resonance energy transfer (FRET) imaging techniques has provided a readout of the dynamics of signal transduction in dendritic spines undergoing structural plasticity. These studies reveal the signalling pathways relaying Ca2+ to the functional and structural plasticity of dendritic spines.

Excitatory, Inhibitory, and Structural Plasticity Produce Correlated Connectivity in Random Networks Trained to Solve Paired-Stimulus Tasks

Bourjaily, Mark A.; Miller, Paul
Fonte: Frontiers Research Foundation Publicador: Frontiers Research Foundation
Tipo: Artigo de Revista Científica
Publicado em 12/09/2011 Português
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486.901%
The pattern of connections among cortical excitatory cells with overlapping arbors is non-random. In particular, correlations among connections produce clustering – cells in cliques connect to each other with high probability, but with lower probability to cells in other spatially intertwined cliques. In this study, we model initially randomly connected sparse recurrent networks of spiking neurons with random, overlapping inputs, to investigate what functional and structural synaptic plasticity mechanisms sculpt network connections into the patterns measured in vitro. Our Hebbian implementation of structural plasticity causes a removal of connections between uncorrelated excitatory cells, followed by their random replacement. To model a biconditional discrimination task, we stimulate the network via pairs (A + B, C + D, A + D, and C + B) of four inputs (A, B, C, and D). We find networks that produce neurons most responsive to specific paired inputs – a building block of computation and essential role for cortex – contain the excessive clustering of excitatory synaptic connections observed in cortical slices. The same networks produce the best performance in a behavioral readout of the networks’ ability to complete the task. A plasticity mechanism operating on inhibitory connections...

Stress and anxiety: Structural plasticity and epigenetic regulation as a consequence of stress

McEwen, Bruce S.; Eiland, Lisa; Hunter, Richard G.; Miller, Melinda M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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477.4909%
The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor. The adult, as well as developing brain, possess a remarkable ability to show reversible structural and functional plasticity in response to stressful and other experiences, including neuronal replacement, dendritic remodeling, and synapse turnover. This is particularly evident in the hippocampus, where all three types of structural plasticity have been recognized and investigated, using a combination of morphological, molecular, pharmacological, electrophysiological and behavioral approaches. The amygdala and the prefrontal cortex, brain regions involved in anxiety and fear, mood, cognitive function and behavioral control, also show structural plasticity. Acute and chronic stress cause an imbalance of neural circuitry subserving cognition, decision making, anxiety and mood that can increase or decrease expression of those behaviors and behavioral states. In the short term, such as for increased fearful vigilance and anxiety in a threatening environment, these changes may be adaptive; but, if the danger passes and the behavioral state persists along with the changes in neural circuitry...

Spike-Timing Dependence of Structural Plasticity Explains Cooperative Synapse Formation in the Neocortex

Deger, Moritz; Helias, Moritz; Rotter, Stefan; Diesmann, Markus
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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477.4909%
Structural plasticity governs the long-term development of synaptic connections in the neocortex. While the underlying processes at the synapses are not fully understood, there is strong evidence that a process of random, independent formation and pruning of excitatory synapses can be ruled out. Instead, there must be some cooperation between the synaptic contacts connecting a single pre- and postsynaptic neuron pair. So far, the mechanism of cooperation is not known. Here we demonstrate that local correlation detection at the postsynaptic dendritic spine suffices to explain the synaptic cooperation effect, without assuming any hypothetical direct interaction pathway between the synaptic contacts. Candidate biomolecular mechanisms for dendritic correlation detection have been identified previously, as well as for structural plasticity based thereon. By analyzing and fitting of a simple model, we show that spike-timing correlation dependent structural plasticity, without additional mechanisms of cross-synapse interaction, can reproduce the experimentally observed distributions of numbers of synaptic contacts between pairs of neurons in the neocortex. Furthermore, the model yields a first explanation for the existence of both transient and persistent dendritic spines and allows to make predictions for future experiments.

Mechanisms of Psychostimulant-Induced Structural Plasticity

Golden, Sam A.; Russo, Scott J.
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /10/2012 Português
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Psychostimulants robustly induce alterations in neuronal structural plasticity throughout brain reward circuits. However, despite our extensive understanding of how these circuits modulate motivated behavior, it is still unclear whether structural plasticity within these regions drives pathological behavioral responses in addiction. Although these structural changes have been subjected to an exhaustive phenomenological characterization, we still have a limited understanding of the molecular mechanisms regulating their induction and the functional relevance of such changes in mediating addiction-like behavior. Here we have highlighted the known molecular pathways and intracellular signaling cascades that regulate psychostimulant-induced changes in neuronal morphology and synaptic restructuring, and we discuss them in the larger context of addiction behavior.

Bidirectional influence of sodium channel activation on NMDA receptor–dependent cerebrocortical neuron structural plasticity

George, Joju; Baden, Daniel G.; Gerwick, William H.; Murray, Thomas F.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
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475.50965%
Neuronal activity regulates brain development and synaptic plasticity through N-methyl-d-aspartate receptors (NMDARs) and calcium-dependent signaling pathways. Intracellular sodium ([Na+]i) also exerts a regulatory influence on NMDAR channel activity, and [Na+]i may, therefore, function as a signaling molecule. In an attempt to mimic the influence of neuronal activity on synaptic plasticity, we used brevetoxin-2 (PbTx-2), a voltage-gated sodium channel (VGSC) gating modifier, to manipulate [Na+]i in cerebrocortical neurons. The acute application of PbTx-2 produced concentration-dependent increments in both intracellular [Na+] and [Ca2+]. Pharmacological evaluation showed that PbTx-2–induced Ca2+ influx primarily involved VGSC activation and NMDAR-mediated entry. Additionally, PbTx-2 robustly potentiated NMDA-induced Ca2+ influx. PbTx-2–exposed neurons showed enhanced neurite outgrowth, increased dendritic arbor complexity, and increased dendritic filopodia density. The appearance of spontaneous calcium oscillations, reflecting synchronous neuronal activity, was accelerated by PbTx-2 treatment. Parallel to this response, PbTx-2 increased cerebrocortical neuron synaptic density. PbTx-2 stimulation of neurite outgrowth, dendritic arborization...

Homeostatic structural plasticity can account for topology changes following deafferentation and focal stroke

Butz, Markus; Steenbuck, Ines D.; van Ooyen, Arjen
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 16/10/2014 Português
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481.24043%
After brain lesions caused by tumors or stroke, or after lasting loss of input (deafferentation), inter- and intra-regional brain networks respond with complex changes in topology. Not only areas directly affected by the lesion but also regions remote from the lesion may alter their connectivity—a phenomenon known as diaschisis. Changes in network topology after brain lesions can lead to cognitive decline and increasing functional disability. However, the principles governing changes in network topology are poorly understood. Here, we investigated whether homeostatic structural plasticity can account for changes in network topology after deafferentation and brain lesions. Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low. Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology. In accordance with experimental and clinical data, we found that after partial deafferentation, the network as a whole became more random, although it maintained its small-world topology...

Shaping inhibition: activity dependent structural plasticity of GABAergic synapses

Flores, Carmen E.; Méndez, Pablo
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 27/10/2014 Português
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477.4909%
Inhibitory transmission through the neurotransmitter γ-aminobutyric acid (GABA) shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons.

Structural plasticity: mechanisms and contribution to developmental psychiatric disorders

Bernardinelli, Yann; Nikonenko, Irina; Muller, Dominique
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 03/11/2014 Português
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Synaptic plasticity mechanisms are usually discussed in terms of changes in synaptic strength. The capacity of excitatory synapses to rapidly modify the membrane expression of glutamate receptors in an activity-dependent manner plays a critical role in learning and memory processes by re-distributing activity within neuronal networks. Recent work has however also shown that functional plasticity properties are associated with a rewiring of synaptic connections and a selective stabilization of activated synapses. These structural aspects of plasticity have the potential to continuously modify the organization of synaptic networks and thereby introduce specificity in the wiring diagram of cortical circuits. Recent work has started to unravel some of the molecular mechanisms that underlie these properties of structural plasticity, highlighting an important role of signaling pathways that are also major candidates for contributing to developmental psychiatric disorders. We review here some of these recent advances and discuss the hypothesis that alterations of structural plasticity could represent a common mechanism contributing to the cognitive and functional defects observed in diseases such as intellectual disability, autism spectrum disorders and schizophrenia.

Structural plasticity in mesencephalic dopaminergic neurons produced by drugs of abuse: critical role of BDNF and dopamine

Collo, Ginetta; Cavalleri, Laura; Spano, PierFranco
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 25/11/2014 Português
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483.94844%
Mesencephalic dopaminergic neurons were suggested to be a critical physiopathology substrate for addiction disorders. Among neuroadaptive processes to addictive drugs, structural plasticity has attracted attention. While structural plasticity occurs at both pre- and post-synaptic levels in the mesolimbic dopaminergic system, the present review focuses only on dopaminergic neurons. Exposures to addictive drugs determine two opposite structural responses, hypothrophic plasticity produced by opioids and cannabinoids (in particular during the early withdrawal phase) and hypertrophic plasticity, mostly driven by psychostimulants and nicotine. In vitro and in vivo studies identified BDNF and extracellular dopamine as two critical factors in determining structural plasticity, the two molecules sharing similar intracellular pathways involved in cell soma and dendrite growth, the MEK-ERK1/2 and the PI3K-Akt-mTOR, via preferential activation of TrkB and dopamine D3 receptors, respectively. At present information regarding specific structural changes associated to the various stages of the addiction cycle is incomplete. Encouraging neuroimaging data in humans indirectly support the preclinical evidence of hypotrophic and hypertrophic effects...

Role of Synaptic Structural Plasticity in Impairments of Spatial Learning and Memory Induced by Developmental Lead Exposure in Wistar Rats

Xiao, Yongmei; Fu, Hongjun; Han, Xiaojie; Hu, Xiaoxia; Gu, Huaiyu; Chen, Yilin; Wei, Qing; Hu, Qiansheng
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 23/12/2014 Português
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481.24043%
Lead (Pb) is found to impair cognitive function. Synaptic structural plasticity is considered to be the physiological basis of synaptic functional plasticity and has been recently found to play important roles in learning and memory. To study the effect of Pb on spatial learning and memory at different developmental stages, and its relationship with alterations of synaptic structural plasticity, postnatal rats were randomly divided into three groups: Control; Pre-weaning Pb (Parents were exposed to 2 mM PbCl2 3 weeks before mating until weaning of pups); Post-weaning Pb (Weaned pups were exposed to 2 mM PbCl2 for 9 weeks). The spatial learning and memory of rats was measured by Morris water maze (MWM) on PND 85–90. Rat pups in Pre-weaning Pb and Post-weaning Pb groups performed significantly worse than those in Control group (p<0.05). However, there was no significant difference in the performance of MWM between the two Pb-exposure groups. Before MWM (PND 84), the number of neurons and synapses significantly decreased in Pre-weaning Pb group, but not in Post-weaning Pb group. After MWM (PND 91), the number of synapses in Pre-weaning Pb group increased significantly, but it was still less than that of Control group (p<0.05); the number of synapses in Post-weaning Pb group was also less than that of Control group (p<0.05)...

Structural plasticity of dendritic spines

Bosch, Miquel; Hayashi, Yasunori
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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475.26527%
Dendritic spines are small mushroom-like protrusions arising from neurons where most excitatory synapses reside. Their peculiar shape suggests that spines can serve as an autonomous postsynaptic compartment that isolates chemical and electrical signaling. How neuronal activity modifies the morphology of the spine and how these modifications affect synaptic transmission and plasticity are intriguing issues. Indeed, the induction of long-term potentiation (LTP) or depression (LTD) is associated with the enlargement or shrinkage of the spine, respectively. This structural plasticity is mainly controlled by actin filaments, the principal cytoskeletal component of the spine. Here we review the pioneering microscopic studies examining the structural plasticity of spines and propose how changes in actin treadmilling might regulate spine morphology.

Diffusion MRI of Structural Brain Plasticity Induced by a Learning and Memory Task

Blumenfeld-Katzir, Tamar; Dagan, Michael; Assaf, Yaniv; Pasternak, Ofer
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
475.6891%
Background: Activity-induced structural remodeling of dendritic spines and glial cells was recently proposed as an important factor in neuroplasticity and suggested to accompany the induction of long-term potentiation (LTP). Although T1 and diffusion MRI have been used to study structural changes resulting from long-term training, the cellular basis of the findings obtained and their relationship to neuroplasticity are poorly understood. Methodology/Principal Finding: Here we used diffusion tensor imaging (DTI) to examine the microstructural manifestations of neuroplasticity in rats that performed a spatial navigation task. We found that DTI can be used to define the selective localization of neuroplasticity induced by different tasks and that this process is age-dependent in cingulate cortex and corpus callosum and age-independent in the dentate gyrus. Conclusion/Significance: We relate the observed DTI changes to the structural plasticity that occurs in astrocytes and discuss the potential of MRI for probing structural neuroplasticity and hence indirectly localizing LTP.

Long-term activity-induced changes in the brain : a study of translational regulation and structural plasticity

Govindarajan, Arvind
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 154 leaves; 9248211 bytes; 9256714 bytes; application/pdf; application/pdf
Português
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Long-lasting changes must take place in the brain to store the skills and memories that have been learned by the organism throughout its history. Long-term memory (LTM), and its cellular correlate, the late-phase of long-term potentiation (L-LTP), require protein synthesis. It has generally been assumed that the regulation of transcription underlies L-LTM and LTM. Chapter 2 of this thesis demonstrates that transgenic mice with inhibited ERK MAP Kinase pathway activity in the cortex and CA1 region of the hippocampus show inhibited LTM and L-LTP. Moreover, the L-LTP phenotype resembles a deficit in translation and not transcription. Experiments using hippocampal cultured cells demonstrate that neuronal activity induces translation of a large number of mRNAs in an ERK MAP Kinase pathway-dependent manner via phosphorylation of the translation factors S6, elF4E and 4E-BP1. Increased phosphorylation of translation factors was observed along with increased translation after the induction of L-LTP; lastly, LTM formation occurred concomitantly with ERK MAP Kinase pathway-dependent phosphorylation of S6 and elF4E. Chapter 3 extends these findings to demonstrate that other stimuli that cause protein synthesis-dependent forms of plasticity also upregulate protein synthesis via the same mechanisms.; (cont.) As some of these stimuli cause L-LTP and others cause L-LTD...