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Regulation of hnRNP A2/B1 and hnRNP K by synaptic activity and BDNF in the hippocampus

Leal, Graciano
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Tese de Doutorado
Português
Relevância na Pesquisa
37.318494%
Synaptic plasticity describes the process by which connections between neurons, or synapses, change in strength. By definition, it is a functional term referring to an increase or decrease in synaptic efficacy, which is accompanied by structural changes at synapses.Long-term potentiation (LTP) is the most studied form of synaptic plasticity and it has been widely recognized that synaptic changes that underpin certain forms of learning and memory may be similar to those involved in the expression of LTP. Some of the structural, biochemical and functional modifications at the synapse associated with synaptic plasticity require activity-dependent transport and translation of dendritic-localized mRNAs, with concomitant alterations in the synaptic proteome. It is becoming evident that dendritic protein synthesis has a crucial role in several forms of synaptic plasticity, including brain-derived neurotrophic factor (BDNF)-mediated LTP. Dendritic transcripts required for local protein synthesis are transported in a repressed state along the microtubule cytoskeleton as components of large messenger ribonucleoprotein complexes (mRNPs). In order to be transported, dendritic mRNAs must contain a cis-acting element in their sequence that is recognized by specific RNA binding proteins that...

Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

LEÃO, R.M.; VON GERSDORFF, H.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
37.191045%
The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that...

Synaptic vesicle pool size, release probability and synaptic depression are sensitive to Ca2+ buffering capacity in the developing rat calyx of Held

Leão,R.M.; von Gersdorff,H.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2009 Português
Relevância na Pesquisa
37.191045%
The calyx of Held, a specialized synaptic terminal in the medial nucleus of the trapezoid body, undergoes a series of changes during postnatal development that prepares this synapse for reliable high frequency firing. These changes reduce short-term synaptic depression during tetanic stimulation and thereby prevent action potential failures during a stimulus train. We measured presynaptic membrane capacitance changes in calyces from young postnatal day 5-7 (p5-7) or older (p10-12) rat pups to examine the effect of calcium buffer capacity on vesicle pool size and the efficiency of exocytosis. Vesicle pool size was sensitive to the choice and concentration of exogenous Ca2+ buffer, and this sensitivity was much stronger in younger animals. Pool size and exocytosis efficiency in p5-7 calyces were depressed by 0.2 mM EGTA to a greater extent than with 0.05 mM BAPTA, even though BAPTA is a 100-fold faster Ca2+ buffer. However, this was not the case for p10-12 calyces. With 5 mM EGTA, exocytosis efficiency was reduced to a much larger extent in young calyces compared to older calyces. Depression of exocytosis using pairs of 10-ms depolarizations was reduced by 0.2 mM EGTA compared to 0.05 mM BAPTA to a similar extent in both age groups. These results indicate a developmentally regulated heterogeneity in the sensitivity of different vesicle pools to Ca2+ buffer capacity. We propose that...

Eye-blink conditioning is associated with changes in synaptic ultrastructure in the rabbit interpositus nuclei

Weeks, Andrew C.W.; Connor, Steve; Hinchcliff, Richard; LeBoutillier, Janelle C.; Thompson, Richard F.; Petit, Ted L.
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /06/2007 Português
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37.441597%
Eye-blink conditioning involves the pairing of a conditioned stimulus (usually a tone) to an unconditioned stimulus (air puff), and it is well established that an intact cerebellum and interpositus nucleus, in particular, are required for this form of classical conditioning. Changes in synaptic number or structure have long been proposed as a mechanism that may underlie learning and memory, but localizing these changes has been difficult. Thus, the current experiment took advantage of the large amount of research conducted on the neural circuitry that supports eye-blink conditioning by examining synaptic changes in the rabbit interpositus nucleus. Synaptic quantifications included total number of synapses per neuron, numbers of excitatory versus inhibitory synapses, synaptic curvature, synaptic perforations, and the maximum length of the synapses. No overall changes in synaptic number, shape, or perforations were observed. There was, however, a significant increase in the length of excitatory synapses in the conditioned animals. This increase in synaptic length was particularly evident in the concave-shaped synapses. These results, together with previous findings, begin to describe a sequence of synaptic change in the interpositus nuclei following eye-blink conditioning that would appear to begin with structural change and end with an increase in synaptic number.

Aβ DISRUPTED SYNAPTIC VESICLE ENDOCYTOSIS IN CULTURED HIPPOCAMPAL NEURONS

Kelly, Brent L.; Ferreira, Adriana
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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37.30603%
Neuronal death leading to gross brain atrophy is commonly seen in Alzheimer’s disease (AD) patients. Yet, it is becoming increasingly apparent that the pathogenesis of AD involves early and more discrete synaptic changes in affected brain areas. However, the molecular mechanisms that underlie such synaptic dysfunction remain largely unknown. Recently, we have identified dynamin 1, a protein that plays a critical role in synaptic vesicle endocytosis, and hence, in the signaling properties of the synapse, as a potential molecular determinant of such dysfunction in AD. In the present study, we analyzed beta-amyloid (Aβ)-induced changes in synaptic vesicle recycling in cultured hippocampal neurons. Our results showed that Aβ, the main component of senile plaques, caused ultrastructural changes indicative of impaired synaptic vesicle endocytosis in cultured hippocampal neurons that have been stimulated by depolarization with high potassium. In addition, Aβ led to the accumulation of amphiphysin in membrane fractions from stimulated hippocampal neurons. Moreover, experiments using FM1-43 showed reduced dye uptake in stimulated hippocampal neurons treated with Aβ when compared to untreated stimulated controls. Similar results were obtained using a dynamin 1 inhibitory peptide suggesting that dynamin 1 depletion caused deficiency in synaptic vesicle recycling not only in Drosophila but also in mammalian neurons. Collectively...

Receptor-associated proteins and synaptic plasticity

Bruneau, Emile G.; Esteban, Jose A.; Akaaboune, Mohammed
Fonte: The Federation of American Societies for Experimental Biology Publicador: The Federation of American Societies for Experimental Biology
Tipo: Artigo de Revista Científica
Publicado em /03/2009 Português
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37.348467%
Changes in synaptic strength are important for synaptic development and synaptic plasticity. Most directly responsible for these synaptic changes are alterations in synaptic receptor number and density. Although alterations in receptor density mediated by the insertion, lateral mobility, removal, and recycling of receptors have been extensively studied, the dynamics and regulators of intracellular scaffolding proteins have only recently begun to be illuminated. In particular, a closer look at the receptor-associated proteins, which bind to receptors and are necessary for their synaptic localization and clustering, has revealed broader functions than previously thought and some rather unexpected thematic similarities. More than just “placeholders” or members of a passive protein “scaffold,” receptor-associated proteins in every synapse studied have been shown to provide a number of signaling roles. In addition, the most recent state-of-the-art imaging has revealed that receptor-associated proteins are highly dynamic and are involved in regulating synaptic receptor density. Together, these results challenge the view that receptor-associated proteins are members of a static and stable scaffold and argue that their dynamic mobility may be essential for regulating activity-dependent changes in synaptic strength.—Bruneau...

Addictive Nicotine Alters Local Circuit Inhibition During the Induction of In Vivo Hippocampal Synaptic Potentiation

Zhang, Tao A.; Tang, Jianrong; Pidoplichko, Volodymyr I.; Dani, John A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 05/05/2010 Português
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37.21581%
The drug addiction process shares many commonalities with normal learning and memory. Addictive drugs subvert normal synaptic plasticity mechanisms, and the consequent synaptic changes underlie long-lasting modifications in behavior that accrue during the progression from drug use to addiction. Supporting this hypothesis, it was recently shown that nicotine administered to freely moving mice induces long-term synaptic potentiation of the perforant path connection to granule cells of the dentate gyrus. The perforant path carries place and spatial information that links the environment to drug taking. An example of that association is the nicotine induced synaptic potentiation of the perforant path that was found to underlie nicotine conditioned place preference. The present study examines nicotine’s influence over local GABAergic inhibition within the dentate gyrus during the drug induced synaptic potentiation. In vivo recordings from freely moving mice suggested that both feedforward and feedback inhibition onto granules cells was diminished by nicotine during the induction of synaptic potentiation. In vitro brain slice studies indicated that nicotine altered local circuit inhibition within the dentate gyrus leading to disinhibition of granule cells. These changes in local inhibition contributed to nicotine induced in vivo synaptic potentiation...

Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

Valdez, Gregorio; Tapia, Juan C.; Kang, Hyuno; Clemenson, Gregory D.; Gage, F. H.; Lichtman, Jeff W.; Sanes, Joshua R.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
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37.191045%
The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice revealed a variety of age-related structural alterations, including axonal swellings, sprouting, synaptic detachment, partial or complete withdrawal of axons from some postsynaptic sites, and fragmentation of the postsynaptic specialization. Alterations were significant by 18 mo of age and severe by 24 mo. A life-long calorie-restricted diet significantly decreased the incidence of pre- and postsynaptic abnormalities in 24-mo-old mice and attenuated age-related loss of motor neurons and turnover of muscle fibers. One month of exercise (wheel running) in 22-mo-old mice also reduced age-related synaptic changes but had no effect on motor neuron number or muscle fiber turnover. Time-lapse imaging in vivo revealed that exercise partially reversed synaptic alterations that had already occurred. These results demonstrate a critical effect of aging on synaptic structure and provide evidence that interventions capable of extending health span and lifespan can partially reverse these age-related synaptic changes.

Synaptic changes in the brain of subjects with schizophrenia

Faludi, Gábor; Mirnics, Károly
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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37.21581%
Clinical, epidemiological, neuroimaging and postmortem data all suggest schizophrenia is a neurodevelopmental disorder, and that synaptic disturbances might play a critical role in developing the disease. In 1982 Feinberg proposed that the schizophrenia might arise as a result of abnormal synaptic pruning. His hypothesis has survived 40 years of accumulated data, and we review the critical findings related to synaptic dysfunction of schizophrenia. While it is clear that synaptic disturbances are integral and important for understanding the pathophysiology of schizophrenia, it has also become obvious that synaptic disturbances cannot be studied and understood as an independent disease hallmark, but only as a part of a complex network of homeostatic events. Development, glial-neural interaction, changes in energy homeostasis, diverse genetic predisposition, neuroimmune processes and environmental influences all can tip the delicate homeostatic balance of the synaptic morphology and connectivity in a uniquely individual fashion, thus contributing to the emergence of the various symptoms of this devastating disorder. Finally, we argue that based on a predominant change in gene expression pattern we can broadly sub-stratify schizophrenia into “synaptic” “oligodendroglial”...

Calcium-based plasticity model explains sensitivity of synaptic changes to spike pattern, rate, and dendritic location

Graupner, Michael; Brunel, Nicolas
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
47.03301%
Multiple stimulation protocols have been found to be effective in changing synaptic efficacy by inducing long-term potentiation or depression. In many of those protocols, increases in postsynaptic calcium concentration have been shown to play a crucial role. However, it is still unclear whether and how the dynamics of the postsynaptic calcium alone determine the outcome of synaptic plasticity. Here, we propose a calcium-based model of a synapse in which potentiation and depression are activated above calcium thresholds. We show that this model gives rise to a large diversity of spike timing-dependent plasticity curves, most of which have been observed experimentally in different systems. It accounts quantitatively for plasticity outcomes evoked by protocols involving patterns with variable spike timing and firing rate in hippocampus and neocortex. Furthermore, it allows us to predict that differences in plasticity outcomes in different studies are due to differences in parameters defining the calcium dynamics. The model provides a mechanistic understanding of how various stimulation protocols provoke specific synaptic changes through the dynamics of calcium concentration and thresholds implementing in simplified fashion protein signaling cascades...

Distinct sensory requirements for unimodal and cross-modal homeostatic synaptic plasticity

He, Kaiwen; Petrus, Emily; Gammon, Nicholas; Lee, Hey-Kyoung
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 20/06/2012 Português
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Loss of a sensory modality elicits both unimodal changes in the deprived cortex and cross-modal alterations in the remaining sensory systems. Unimodal changes are proposed to recruit the deprived cortex for processing the remaining senses, while cross-modal changes are thought to refine processing of spared senses. Hence coordinated unimodal and cross-modal changes are likely beneficial. Despite this expectation, we report in mice that losing behaviorally relevant patterned vision is sufficient to trigger cross-modal synaptic changes in the primary somatosensory cortex barrel fields (S1BFs), but is insufficient to drive unimodal synaptic plasticity in visual cortex (V1), which requires a complete loss of visual activity. In addition, cross-modal changes depend on whisker inputs. Our results demonstrate that unimodal and cross-modal synaptic plasticity occur independently of each other and rely on distinct sensory requirements.

Brain Region Specific Pre-Synaptic and Post-Synaptic Degeneration Are Early Components of Neuropathology in Prion Disease

Šišková, Zuzana; Reynolds, Richard A.; O’Connor, Vincent; Perry, V. Hugh
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 30/01/2013 Português
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37.23911%
Synaptic abnormalities, one of the key features of prion disease pathogenesis, gives rise to functional deficits and contributes to the devastating clinical outcome. The synaptic compartment is the first to succumb in several neurodegenerative diseases linked with protein misfolding but the mechanisms underpinning this are poorly defined. In our current study we document that a focal intrahippocampal injection of the mouse-adapted 22L scrapie strain produces a complex, region-specific pathology in the brain. Our findings reveal that early synaptic changes in the stratum radiatum of the hippocampus, identical to those observed with the ME7 strain, occur when 22L strain is introduced into the hippocampus. The pathology was defined by degenerating Type I pre-synaptic elements progressively enveloped by the post-synaptic density of the dendritic spine. In contrast, the pathology in the cerebellum suggested that dendritic disintegration rather than pre-synaptic abnormalities dominate the early degenerative changes associated with the Purkinje cells. Indeed, both of the major synaptic inputs into the cerebellum, which arise from the parallel and climbing fibers, remained intact even at late stage disease. Immunolabeling with pathway selective antibodies reinforced these findings. These observations demonstrate that neuronal vulnerability to pathological protein misfolding is strongly dependent on the structure and function of the target neurons.

Synaptic and Intrinsic Homeostatic Mechanisms Cooperate to Increase L2/3 Pyramidal Neuron Excitability During a Late Phase of Critical Period Plasticity

Lambo, Mary E.; Turrigiano, Gina G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/05/2013 Português
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37.33315%
Visual deprivation profoundly affects visual cortical response properties, but the activity-dependent plasticity mechanisms that underlie these changes are poorly understood. Monocular deprivation (MD) induces ocular dominance (OD) shifts through biphasic changes in cortical excitability, first decreasing responsiveness to the deprived eye, then slowly increasing responsiveness to both the deprived and spared eyes. It has been suggested that this slow gain of responsiveness is due to homeostatic synaptic scaling, but this prediction has not been tested directly. Here we show that, in rat monocular and binocular primary visual cortex (V1m and V1b), postsynaptic strength onto layer 2/3 (L2/3) pyramidal neurons is modulated in a biphasic manner by MD, first undergoing a net decrease after 1 and 2 days MD, increasing back to baseline after 3 days, and finally undergoing a net potentiation between 3 and 6 days. The time course and direction of these synaptic changes match well the known changes in visual responsiveness during OD plasticity. Viral-mediated delivery of the GluA2 C-tail in vivo blocked these synaptic changes, indicating that, like synaptic scaling in vitro, AMPA receptor trafficking via the GluA2 C-tail is required for the delayed increase in postsynaptic strength. Finally...

Synaptic competition in structural plasticity and cognitive function

Ramiro-Cortés, Yazmín; Hobbiss, Anna F.; Israely, Inbal
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
Publicado em 05/01/2014 Português
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37.191045%
Connections between neurons can undergo long-lasting changes in synaptic strength correlating with changes in structure. These events require the synthesis of new proteins, the availability of which can lead to cooperative and competitive interactions between synapses for the expression of plasticity. These processes can occur over limited spatial distances and temporal periods, defining dendritic regions over which activity may be integrated and could lead to the physical rewiring of synapses into functional groups. Such clustering of inputs may increase the computational power of neurons by allowing information to be combined in a greater than additive manner. The availability of new proteins may be a key modulatory step towards activity-dependent, long-term growth or elimination of spines necessary for remodelling of connections. Thus, the aberrant growth or shrinkage of dendritic spines could occur if protein levels are misregulated. Indeed, such perturbations can be seen in several mental retardation disorders, wherein either too much or too little protein translation exists, matching an observed increase or decrease in spine density, respectively. Cellular events which alter protein availability could relieve a constraint on synaptic competition and disturb synaptic clustering mechanisms. These changes may be detrimental to modifications in neural circuitry following activity.

Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction

van Huijstee, Aile N.; Mansvelder, Huibert D.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 20/01/2015 Português
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37.384849%
Addictive drugs remodel the brain’s reward circuitry, the mesocorticolimbic dopamine (DA) system, by inducing widespread adaptations of glutamatergic synapses. This drug-induced synaptic plasticity is thought to contribute to both the development and the persistence of addiction. This review highlights the synaptic modifications that are induced by in vivo exposure to addictive drugs and describes how these drug-induced synaptic changes may contribute to the different components of addictive behavior, such as compulsive drug use despite negative consequences and relapse. Initially, exposure to an addictive drug induces synaptic changes in the ventral tegmental area (VTA). This drug-induced synaptic potentiation in the VTA subsequently triggers synaptic changes in downstream areas of the mesocorticolimbic system, such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC), with further drug exposure. These glutamatergic synaptic alterations are then thought to mediate many of the behavioral symptoms that characterize addiction. The later stages of glutamatergic synaptic plasticity in the NAc and in particular in the PFC play a role in maintaining addiction and drive relapse to drug-taking induced by drug-associated cues. Remodeling of PFC glutamatergic circuits can persist into adulthood...

Tracking slow modulations in synaptic gain using dynamic causal modelling: Validation in epilepsy

Papadopoulou, Margarita; Leite, Marco; van Mierlo, Pieter; Vonck, Kristl; Lemieux, Louis; Friston, Karl; Marinazzo, Daniele
Fonte: Academic Press Publicador: Academic Press
Tipo: Artigo de Revista Científica
Publicado em 15/02/2015 Português
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37.33315%
In this work we propose a proof of principle that dynamic causal modelling can identify plausible mechanisms at the synaptic level underlying brain state changes over a timescale of seconds. As a benchmark example for validation we used intracranial electroencephalographic signals in a human subject. These data were used to infer the (effective connectivity) architecture of synaptic connections among neural populations assumed to generate seizure activity. Dynamic causal modelling allowed us to quantify empirical changes in spectral activity in terms of a trajectory in parameter space — identifying key synaptic parameters or connections that cause observed signals. Using recordings from three seizures in one patient, we considered a network of two sources (within and just outside the putative ictal zone). Bayesian model selection was used to identify the intrinsic (within-source) and extrinsic (between-source) connectivity. Having established the underlying architecture, we were able to track the evolution of key connectivity parameters (e.g., inhibitory connections to superficial pyramidal cells) and test specific hypotheses about the synaptic mechanisms involved in ictogenesis. Our key finding was that intrinsic synaptic changes were sufficient to explain seizure onset...

Learning structure of sensory inputs with synaptic plasticity leads to interference

Chrol-Cannon, Joseph; Jin, Yaochu
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 05/08/2015 Português
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37.27705%
Synaptic plasticity is often explored as a form of unsupervised adaptation in cortical microcircuits to learn the structure of complex sensory inputs and thereby improve performance of classification and prediction. The question of whether the specific structure of the input patterns is encoded in the structure of neural networks has been largely neglected. Existing studies that have analyzed input-specific structural adaptation have used simplified, synthetic inputs in contrast to complex and noisy patterns found in real-world sensory data. In this work, input-specific structural changes are analyzed for three empirically derived models of plasticity applied to three temporal sensory classification tasks that include complex, real-world visual and auditory data. Two forms of spike-timing dependent plasticity (STDP) and the Bienenstock-Cooper-Munro (BCM) plasticity rule are used to adapt the recurrent network structure during the training process before performance is tested on the pattern recognition tasks. It is shown that synaptic adaptation is highly sensitive to specific classes of input pattern. However, plasticity does not improve the performance on sensory pattern recognition tasks, partly due to synaptic interference between consecutively presented input samples. The changes in synaptic strength produced by one stimulus are reversed by the presentation of another...

Long-term changes in synaptic strength along specific intrinsic pathways in the cat visual cortex.

Hirsch, J A; Gilbert, C D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1993 Português
Relevância na Pesquisa
37.243525%
1. The dense system of horizontal connections that arise and course within the striate cortex are thought to inform single cells about stimuli arising in disparate points in visual space and to modulate responses evoked from within the receptive field. To learn whether or not the strength of the horizontal connections could vary over the long term, and if such changes could affect the integration of vertical, interlaminar inputs, we have recorded intracellularly from the superficial layers in slices of the adult cat's visual cortex. 2. The monosynaptic EPSP evoked by stimulating horizontal fibres showed long-term facilitation in twelve of the twenty cells that were conditioned by repetitively pairing synaptic responses with depolarizing pulses of current; the maximum increase observed was 200%. Strong inhibition present in the postsynaptic response usually indicated that facilitation would not occur. 3. In instances where horizontal input evoked both mono- and polysynaptic EPSPs, both early and late events showed facilitation, with the most dramatic enhancement contributed by the polysynaptic components. 4. For the twenty-eight cells whose responses to stimulation of interlaminar as well as horizontal pathways were assessed, all were found to receive non-overlapping inputs from each source. Conditioning produced long-term changes in the strength of the interlaminar inputs. 5. Changes in synaptic strength were usually confined to the conditioned pathway...

Robustness of Learning That Is Based on Covariance-Driven Synaptic Plasticity

Loewenstein, Yonatan
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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37.33257%
It is widely believed that learning is due, at least in part, to long-lasting modifications of the strengths of synapses in the brain. Theoretical studies have shown that a family of synaptic plasticity rules, in which synaptic changes are driven by covariance, is particularly useful for many forms of learning, including associative memory, gradient estimation, and operant conditioning. Covariance-based plasticity is inherently sensitive. Even a slight mistuning of the parameters of a covariance-based plasticity rule is likely to result in substantial changes in synaptic efficacies. Therefore, the biological relevance of covariance-based plasticity models is questionable. Here, we study the effects of mistuning parameters of the plasticity rule in a decision making model in which synaptic plasticity is driven by the covariance of reward and neural activity. An exact covariance plasticity rule yields Herrnstein's matching law. We show that although the effect of slight mistuning of the plasticity rule on the synaptic efficacies is large, the behavioral effect is small. Thus, matching behavior is robust to mistuning of the parameters of the covariance-based plasticity rule. Furthermore, the mistuned covariance rule results in undermatching...

Corticosterone Regulates Synaptic Input Organization of POMC and NPY/AgRP Neurons in Adult Mice

Gyengesi, Erika; Liu, Zhong-Wu; D'Agostino, Giuseppe; Gan, Geliang; Horvath, Tamas L.; Gao, Xiao-Bing; Diano, Sabrina
Fonte: The Endocrine Society Publicador: The Endocrine Society
Tipo: Artigo de Revista Científica
Português
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37.33257%
Changes in circulating hormones, such as leptin and ghrelin, induce alterations in synaptic input organization and electrophysiological properties of neurons of the arcuate nucleus of the hypothalamus. To assess whether changes in circulating glucocorticoids also alter synaptic arrangement and membrane potential properties, we studied the effect of adrenalectomy (ADX) and corticosterone replacement in mice on the proopiomelanocortin (POMC) and neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons of the hypothalamic arcuate nucleus. ADX reduced the number of symmetric, putative inhibitory synapses onto POMC neurons and the number of asymmetric, putative excitatory synapses onto NPY/AgRP neurons. Corticosterone replacement in ADX mice to levels similar to sham-operated animals restored the number of synapses onto POMC and NPY/AgRP neurons to that seen in sham-operated controls. The alterations in the synaptic arrangement in ADX mice were not due to their decrease in food intake as evidenced by the synaptic analysis of the pair-fed control animals. In line with the altered synaptic input organization, a depolarization of POMC membrane potential and a hyperpolarization of NPY/AgRP membrane potential were observed in ADX mice compared with their sham-operated controls. All of these changes reverted upon corticosterone replacement. These results reveal that the known orexigenic action of corticosteroids is mediated...