Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus.

PubMed

Stefanescu, Roxana A; Shore, Susan E

2017-03-01

Cholinergic modulation contributes to adaptive sensory processing by controlling spontaneous and stimulus-evoked neural activity and long-term synaptic plasticity. In the dorsal cochlear nucleus (DCN), in vitro activation of muscarinic acetylcholine receptors (mAChRs) alters the spontaneous activity of DCN neurons and interacts with N -methyl-d-aspartate (NMDA) and endocannabinoid receptors to modulate the plasticity of parallel fiber synapses onto fusiform cells by converting Hebbian long-term potentiation to anti-Hebbian long-term depression. Because noise exposure and tinnitus are known to increase spontaneous activity in fusiform cells as well as alter stimulus timing-dependent plasticity (StTDP), it is important to understand the contribution of mAChRs to in vivo spontaneous activity and plasticity in fusiform cells. In the present study, we blocked mAChRs actions by infusing atropine, a mAChR antagonist, into the DCN fusiform cell layer in normal hearing guinea pigs. Atropine delivery leads to decreased spontaneous firing rates and increased synchronization of fusiform cell spiking activity. Consistent with StTDP alterations observed in tinnitus animals, atropine infusion induced a dominant pattern of inversion of StTDP mean population learning rule from a Hebbian to an anti-Hebbian profile. Units preserving their initial Hebbian learning rules shifted toward more excitatory changes in StTDP, whereas units with initial suppressive learning rules transitioned toward a Hebbian profile. Together, these results implicate muscarinic cholinergic modulation as a factor in controlling in vivo fusiform cell baseline activity and plasticity, suggesting a central role in the maladaptive plasticity associated with tinnitus pathology. NEW & NOTEWORTHY This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the dorsal cochlear nucleus coupled with simultaneous recordings of neural activity to clarify the contribution of

Emergence of network structure due to spike-timing-dependent plasticity in recurrent neuronal networks IV: structuring synaptic pathways among recurrent connections.

PubMed

Gilson, Matthieu; Burkitt, Anthony N; Grayden, David B; Thomas, Doreen A; van Hemmen, J Leo

2009-12-01

In neuronal networks, the changes of synaptic strength (or weight) performed by spike-timing-dependent plasticity (STDP) are hypothesized to give rise to functional network structure. This article investigates how this phenomenon occurs for the excitatory recurrent connections of a network with fixed input weights that is stimulated by external spike trains. We develop a theoretical framework based on the Poisson neuron model to analyze the interplay between the neuronal activity (firing rates and the spike-time correlations) and the learning dynamics, when the network is stimulated by correlated pools of homogeneous Poisson spike trains. STDP can lead to both a stabilization of all the neuron firing rates (homeostatic equilibrium) and a robust weight specialization. The pattern of specialization for the recurrent weights is determined by a relationship between the input firing-rate and correlation structures, the network topology, the STDP parameters and the synaptic response properties. We find conditions for feed-forward pathways or areas with strengthened self-feedback to emerge in an initially homogeneous recurrent network.

Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity.

PubMed

Pauly, Thorsten; Ratliff, Miriam; Pietrowski, Eweline; Neugebauer, Rainer; Schlicksupp, Andrea; Kirsch, Joachim; Kuhse, Jochen

2008-07-16

Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.

Activity-Dependent Shedding of the NMDA Receptor Glycine Binding Site by Matrix Metalloproteinase 3: A PUTATIVE Mechanism of Postsynaptic Plasticity

PubMed Central

Pietrowski, Eweline; Neugebauer, Rainer; Schlicksupp, Andrea; Kirsch, Joachim; Kuhse, Jochen

2008-01-01

Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS. PMID:18629001

Temperature dependence of plastic scintillators

NASA Astrophysics Data System (ADS)

Peralta, L.

2018-03-01

Plastic scintillator detectors have been studied as dosimeters, since they provide a cost-effective alternative to conventional ionization chambers. Several articles have reported undesired response dependencies on beam energy and temperature, which provides the motivation to determine appropriate correction factors. In this work, we studied the light yield temperature dependency of four plastic scintillators, BCF-10, BCF-60, BC-404, RP-200A and two clear fibers, BCF-98 and SK-80. Measurements were made using a 50 kVp X-ray beam to produce the scintillation and/or radioluminescence signal. The 0 to 40 °C temperature range was scanned for each scintillator, and temperature coefficients were obtained.

Activity-dependent stochastic resonance in recurrent neuronal networks

NASA Astrophysics Data System (ADS)

Volman, Vladislav

2009-03-01

An important source of noise for neuronal networks is that of the stochastic nature of synaptic transmission. In particular, there can occur spontaneous asynchronous release of neurotransmitter at a rate that is strongly dependent on the presynaptic Ca2+ concentration and hence strongly dependent on the rate of spike induced Ca2+. Here it is shown that this noise can lead to a new form of stochastic resonance for local circuits consisting of roughly 100 neurons - a ``microcolumn''- coupled via noisy plastic synapses. Furthermore, due to the plastic coupling and activity-dependent noise component, the detection of weak stimuli will also depend on the structure of the latter. In addition, the circuit can exhibit short-term memory, by which we mean that spiking will continue to occur for a transient period following removal of the stimulus. These results can be directly tested in experiments on cultured networks.

Structural Synaptic Plasticity Has High Memory Capacity and Can Explain Graded Amnesia, Catastrophic Forgetting, and the Spacing Effect

PubMed Central

Knoblauch, Andreas; Körner, Edgar; Körner, Ursula; Sommer, Friedrich T.

2014-01-01

Although already William James and, more explicitly, Donald Hebb's theory of cell assemblies have suggested that activity-dependent rewiring of neuronal networks is the substrate of learning and memory, over the last six decades most theoretical work on memory has focused on plasticity of existing synapses in prewired networks. Research in the last decade has emphasized that structural modification of synaptic connectivity is common in the adult brain and tightly correlated with learning and memory. Here we present a parsimonious computational model for learning by structural plasticity. The basic modeling units are “potential synapses” defined as locations in the network where synapses can potentially grow to connect two neurons. This model generalizes well-known previous models for associative learning based on weight plasticity. Therefore, existing theory can be applied to analyze how many memories and how much information structural plasticity can store in a synapse. Surprisingly, we find that structural plasticity largely outperforms weight plasticity and can achieve a much higher storage capacity per synapse. The effect of structural plasticity on the structure of sparsely connected networks is quite intuitive: Structural plasticity increases the “effectual network connectivity”, that is, the network wiring that specifically supports storage and recall of the memories. Further, this model of structural plasticity produces gradients of effectual connectivity in the course of learning, thereby explaining various cognitive phenomena including graded amnesia, catastrophic forgetting, and the spacing effect. PMID:24858841

Spike Train Auto-Structure Impacts Post-Synaptic Firing and Timing-Based Plasticity

PubMed Central

Scheller, Bertram; Castellano, Marta; Vicente, Raul; Pipa, Gordon

2011-01-01

Cortical neurons are typically driven by several thousand synapses. The precise spatiotemporal pattern formed by these inputs can modulate the response of a post-synaptic cell. In this work, we explore how the temporal structure of pre-synaptic inhibitory and excitatory inputs impact the post-synaptic firing of a conductance-based integrate and fire neuron. Both the excitatory and inhibitory input was modeled by renewal gamma processes with varying shape factors for modeling regular and temporally random Poisson activity. We demonstrate that the temporal structure of mutually independent inputs affects the post-synaptic firing, while the strength of the effect depends on the firing rates of both the excitatory and inhibitory inputs. In a second step, we explore the effect of temporal structure of mutually independent inputs on a simple version of Hebbian learning, i.e., hard bound spike-timing-dependent plasticity. We explore both the equilibrium weight distribution and the speed of the transient weight dynamics for different mutually independent gamma processes. We find that both the equilibrium distribution of the synaptic weights and the speed of synaptic changes are modulated by the temporal structure of the input. Finally, we highlight that the sensitivity of both the post-synaptic firing as well as the spike-timing-dependent plasticity on the auto-structure of the input of a neuron could be used to modulate the learning rate of synaptic modification. PMID:22203800

Motor Learning Enhances Use-Dependent Plasticity

PubMed Central

2017-01-01

Motor behaviors are shaped not only by current sensory signals but also by the history of recent experiences. For instance, repeated movements toward a particular target bias the subsequent movements toward that target direction. This process, called use-dependent plasticity (UDP), is considered a basic and goal-independent way of forming motor memories. Most studies consider movement history as the critical component that leads to UDP (Classen et al., 1998; Verstynen and Sabes, 2011). However, the effects of learning (i.e., improved performance) on UDP during movement repetition have not been investigated. Here, we used transcranial magnetic stimulation in two experiments to assess plasticity changes occurring in the primary motor cortex after individuals repeated reinforced and nonreinforced actions. The first experiment assessed whether learning a skill task modulates UDP. We found that a group that successfully learned the skill task showed greater UDP than a group that did not accumulate learning, but made comparable repeated actions. The second experiment aimed to understand the role of reinforcement learning in UDP while controlling for reward magnitude and action kinematics. We found that providing subjects with a binary reward without visual feedback of the cursor led to increased UDP effects. Subjects in the group that received comparable reward not associated with their actions maintained the previously induced UDP. Our findings illustrate how reinforcing consistent actions strengthens use-dependent memories and provide insight into operant mechanisms that modulate plastic changes in the motor cortex. SIGNIFICANCE STATEMENT Performing consistent motor actions induces use-dependent plastic changes in the motor cortex. This plasticity reflects one of the basic forms of human motor learning. Past studies assumed that this form of learning is exclusively affected by repetition of actions. However, here we showed that success-based reinforcement signals could

The beneficial effects of treadmill step training on activity-dependent synaptic and cellular plasticity markers after complete spinal cord injury.

PubMed

Ilha, Jocemar; Centenaro, Lígia A; Broetto Cunha, Núbia; de Souza, Daniela F; Jaeger, Mariane; do Nascimento, Patrícia S; Kolling, Janaína; Ben, Juliana; Marcuzzo, Simone; Wyse, Angela T S; Gottfried, Carmem; Achaval, Matilde

2011-06-01

Several studies have shown that treadmill training improves neurological outcomes and promotes plasticity in lumbar spinal cord of spinal animals. The morphological and biochemical mechanisms underlying these phenomena remain unclear. The purpose of this study was to provide evidence of activity-dependent plasticity in spinal cord segment (L5) below a complete spinal cord transection (SCT) at T8-9 in rats in which the lower spinal cord segments have been fully separated from supraspinal control and that subsequently underwent treadmill step training. Five days after SCT, spinal animals started a step-training program on a treadmill with partial body weight support and manual step help. Hindlimb movements were evaluated over time and scored on the basis of the open-field BBB scale and were significantly improved at post-injury weeks 8 and 10 in trained spinal animals. Treadmill training also showed normalization of withdrawal reflex in trained spinal animals, which was significantly different from the untrained animals at post-injury weeks 8 and 10. Additionally, compared to controls, spinal rats had alpha motoneuronal soma size atrophy and reduced synaptophysin protein expression and Na(+), K(+)-ATPase activity in lumbar spinal cord. Step-trained rats had motoneuronal soma size, synaptophysin expression and Na(+), K(+)-ATPase activity similar to control animals. These findings suggest that treadmill step training can promote activity-dependent neural plasticity in lumbar spinal cord, which may lead to neurological improvements without supraspinal descending control after complete spinal cord injury.

Fragile X Mental Retardation Protein and Dendritic Local Translation of the Alpha Subunit of the Calcium/Calmodulin-Dependent Kinase II Messenger RNA Are Required for the Structural Plasticity Underlying Olfactory Learning.

PubMed

Daroles, Laura; Gribaudo, Simona; Doulazmi, Mohamed; Scotto-Lomassese, Sophie; Dubacq, Caroline; Mandairon, Nathalie; Greer, Charles August; Didier, Anne; Trembleau, Alain; Caillé, Isabelle

2016-07-15

In the adult brain, structural plasticity allowing gain or loss of synapses remodels circuits to support learning. In fragile X syndrome, the absence of fragile X mental retardation protein (FMRP) leads to defects in plasticity and learning deficits. FMRP is a master regulator of local translation but its implication in learning-induced structural plasticity is unknown. Using an olfactory learning task requiring adult-born olfactory bulb neurons and cell-specific ablation of FMRP, we investigated whether learning shapes adult-born neuron morphology during their synaptic integration and its dependence on FMRP. We used alpha subunit of the calcium/calmodulin-dependent kinase II (αCaMKII) mutant mice with altered dendritic localization of αCaMKII messenger RNA, as well as a reporter of αCaMKII local translation to investigate the role of this FMRP messenger RNA target in learning-dependent structural plasticity. Learning induces profound changes in dendritic architecture and spine morphology of adult-born neurons that are prevented by ablation of FMRP in adult-born neurons and rescued by an metabotropic glutamate receptor 5 antagonist. Moreover, dendritically translated αCaMKII is necessary for learning and associated structural modifications and learning triggers an FMRP-dependent increase of αCaMKII dendritic translation in adult-born neurons. Our results strongly suggest that FMRP mediates structural plasticity of olfactory bulb adult-born neurons to support olfactory learning through αCaMKII local translation. This reveals a new role for FMRP-regulated dendritic local translation in learning-induced structural plasticity. This might be of clinical relevance for the understanding of critical periods disruption in autism spectrum disorder patients, among which fragile X syndrome is the primary monogenic cause. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Emergence of small-world structure in networks of spiking neurons through STDP plasticity.

PubMed

Basalyga, Gleb; Gleiser, Pablo M; Wennekers, Thomas

2011-01-01

In this work, we use a complex network approach to investigate how a neural network structure changes under synaptic plasticity. In particular, we consider a network of conductance-based, single-compartment integrate-and-fire excitatory and inhibitory neurons. Initially the neurons are connected randomly with uniformly distributed synaptic weights. The weights of excitatory connections can be strengthened or weakened during spiking activity by the mechanism known as spike-timing-dependent plasticity (STDP). We extract a binary directed connection matrix by thresholding the weights of the excitatory connections at every simulation step and calculate its major topological characteristics such as the network clustering coefficient, characteristic path length and small-world index. We numerically demonstrate that, under certain conditions, a nontrivial small-world structure can emerge from a random initial network subject to STDP learning.

Environment- and activity-dependent dopamine neurotransmitter plasticity in the adult substantia nigra.

PubMed

Aumann, Tim D

2016-04-01

The ability of neurons to change the amount or type of neurotransmitter they use, or 'neurotransmitter plasticity', is an emerging new form of adult brain plasticity. For example, it has recently been shown that neurons in the adult rat hypothalamus up- or down-regulate dopamine (DA) neurotransmission in response to the amount of light the animal receives (photoperiod), and that this in turn affects anxiety- and depressive-like behaviors (Dulcis et al., 2013). In this Chapter I consolidate recent evidence from my laboratory suggesting neurons in the adult mouse substantia nigra pars compacta (SNc) also undergo DA neurotransmitter plasticity in response to persistent changes in their electrical activity, including that driven by the mouse's environment or behavior. Specifically, we have shown that the amounts of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) gene promoter activity, TH mRNA and TH protein in SNc neurons increases or decreases after ∼20h of altered electrical activity. Also, infusion of ion-channel agonists or antagonists into the midbrain for 2 weeks results in ∼10% (∼500 neurons) more or fewer TH immunoreactive (TH+) SNc neurons, with no change in the total number of SNc neurons (TH+ and TH-). Targeting ion-channels mediating cell-autonomous pacemaker activity in, or synaptic input and afferent pathways to, SNc neurons are equally effective in this regard. In addition, exposing mice to different environments (sex pairing or environment enrichment) for 1-2 weeks induces ∼10% more or fewer TH+ SNc (and ventral tegmental area or VTA) neurons and this is abolished by concurrent blockade of synaptic transmission in midbrain. Although further research is required to establish SNc (and VTA) DA neurotransmitter plasticity, and to determine whether it alters brain function and behavior, it is an exciting prospect because: (1) It may play important roles in movement, motor learning, reward, motivation, memory and cognition; and (2

Repeated N-Acetylcysteine Administration Alters Plasticity-Dependent Effects of Cocaine

PubMed Central

Madayag, Aric; Lobner, Doug; Kau, Kristen S.; Mantsch, John R.; Abdulhameed, Omer; Hearing, Matthew; Grier, Mark D.; Baker, David A.

2010-01-01

Cocaine produces a persistent reduction in cystine-glutamate exchange via system xc- in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System xc- influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens which, in turn, shapes synaptic activity by stimulating group II metabotropic glutamate autoreceptors. In the present study, we tested the hypothesis that a long-term reduction in system xc- activity is part of the plasticity produced by repeated cocaine that results in the establishment of compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine was administered prior to daily cocaine to determine the impact of increased cystine-glutamate exchange on the development of plasticity-dependent cocaine seeking. Although N-acetylcysteine administered prior to cocaine did not alter the acute effects of cocaine on self-administration or locomotor activity, it prevented behaviors produced by repeated cocaine including escalation of drug intake, behavioral sensitization, and cocaine-primed reinstatement. Because sensitization or reinstatement was not evident even 2–3 weeks after the last injection of N-acetylcysteine, we examined whether N-acetylcysteine administered prior to daily cocaine also prevented the persistent reduction in system xc- activity produced by repeated cocaine. Interestingly, N-acetylcysteine pretreatment prevented cocaine-induced changes in 35S cystine transport via system xc-, basal glutamate, and cocaine-evoked glutamate in the nucleus accumbens when assessed at least three weeks after the last N-acetylcysteine pretreatment. These findings indicate that N-acetylcysteine selectively alters plasticity-dependent behaviors and that normal system xc- activity prevents pathological changes in extracellular glutamate that may be necessary for compulsive drug seeking. PMID:18094234

Emergence of Slow Collective Oscillations in Neural Networks with Spike-Timing Dependent Plasticity

NASA Astrophysics Data System (ADS)

Mikkelsen, Kaare; Imparato, Alberto; Torcini, Alessandro

2013-05-01

The collective dynamics of excitatory pulse coupled neurons with spike-timing dependent plasticity is studied. The introduction of spike-timing dependent plasticity induces persistent irregular oscillations between strongly and weakly synchronized states, reminiscent of brain activity during slow-wave sleep. We explain the oscillations by a mechanism, the Sisyphus Effect, caused by a continuous feedback between the synaptic adjustments and the coherence in the neural firing. Due to this effect, the synaptic weights have oscillating equilibrium values, and this prevents the system from relaxing into a stationary macroscopic state.

Discrete dislocation plasticity analysis of loading rate-dependent static friction.

PubMed

Song, H; Deshpande, V S; Van der Giessen, E

2016-08-01

From a microscopic point of view, the frictional force associated with the relative sliding of rough surfaces originates from deformation of the material in contact, by adhesion in the contact interface or both. We know that plastic deformation at the size scale of micrometres is not only dependent on the size of the contact, but also on the rate of deformation. Moreover, depending on its physical origin, adhesion can also be size and rate dependent, albeit different from plasticity. We present a two-dimensional model that incorporates both discrete dislocation plasticity inside a face-centred cubic crystal and adhesion in the interface to understand the rate dependence of friction caused by micrometre-size asperities. The friction strength is the outcome of the competition between adhesion and discrete dislocation plasticity. As a function of contact size, the friction strength contains two plateaus: at small contact length [Formula: see text], the onset of sliding is fully controlled by adhesion while for large contact length [Formula: see text], the friction strength approaches the size-independent plastic shear yield strength. The transition regime at intermediate contact size is a result of partial de-cohesion and size-dependent dislocation plasticity, and is determined by dislocation properties, interfacial properties as well as by the loading rate.

JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory.

PubMed

Morel, Caroline; Sherrin, Tessi; Kennedy, Norman J; Forest, Kelly H; Avcioglu Barutcu, Seda; Robles, Michael; Carpenter-Hyland, Ezekiel; Alfulaij, Naghum; Standen, Claire L; Nichols, Robert A; Benveniste, Morris; Davis, Roger J; Todorovic, Cedomir

2018-04-11

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JNK-interacting protein 1 (JIP1) scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDAR currents, increased NMDAR-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDAR-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT The results of this study demonstrate that c-Jun N-terminal kinase (JNK) activation induced by the JNK-interacting protein 1 (JIP1) scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study identifies JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDAR-dependent synaptic plasticity and memory. Copyright © 2018 the authors 0270-6474/18/383708-21$15.00/0.

Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules

PubMed Central

Frémaux, Nicolas; Gerstner, Wulfram

2016-01-01

Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide “when” to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators. PMID:26834568

Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules.

PubMed

Frémaux, Nicolas; Gerstner, Wulfram

2015-01-01

Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide "when" to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators.

Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses.

PubMed

Ocker, Gabriel Koch; Litwin-Kumar, Ashok; Doiron, Brent

2015-08-01

The synaptic connectivity of cortical networks features an overrepresentation of certain wiring motifs compared to simple random-network models. This structure is shaped, in part, by synaptic plasticity that promotes or suppresses connections between neurons depending on their joint spiking activity. Frequently, theoretical studies focus on how feedforward inputs drive plasticity to create this network structure. We study the complementary scenario of self-organized structure in a recurrent network, with spike timing-dependent plasticity driven by spontaneous dynamics. We develop a self-consistent theory for the evolution of network structure by combining fast spiking covariance with a slow evolution of synaptic weights. Through a finite-size expansion of network dynamics we obtain a low-dimensional set of nonlinear differential equations for the evolution of two-synapse connectivity motifs. With this theory in hand, we explore how the form of the plasticity rule drives the evolution of microcircuits in cortical networks. When potentiation and depression are in approximate balance, synaptic dynamics depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian STDP these motif interactions create instabilities in synaptic dynamics that either promote or suppress the initial network structure. Our work provides a consistent theoretical framework for studying how spiking activity in recurrent networks interacts with synaptic plasticity to determine network structure.

Self-Organization of Microcircuits in Networks of Spiking Neurons with Plastic Synapses

PubMed Central

Ocker, Gabriel Koch; Litwin-Kumar, Ashok; Doiron, Brent

2015-01-01

The synaptic connectivity of cortical networks features an overrepresentation of certain wiring motifs compared to simple random-network models. This structure is shaped, in part, by synaptic plasticity that promotes or suppresses connections between neurons depending on their joint spiking activity. Frequently, theoretical studies focus on how feedforward inputs drive plasticity to create this network structure. We study the complementary scenario of self-organized structure in a recurrent network, with spike timing-dependent plasticity driven by spontaneous dynamics. We develop a self-consistent theory for the evolution of network structure by combining fast spiking covariance with a slow evolution of synaptic weights. Through a finite-size expansion of network dynamics we obtain a low-dimensional set of nonlinear differential equations for the evolution of two-synapse connectivity motifs. With this theory in hand, we explore how the form of the plasticity rule drives the evolution of microcircuits in cortical networks. When potentiation and depression are in approximate balance, synaptic dynamics depend on weighted divergent, convergent, and chain motifs. For additive, Hebbian STDP these motif interactions create instabilities in synaptic dynamics that either promote or suppress the initial network structure. Our work provides a consistent theoretical framework for studying how spiking activity in recurrent networks interacts with synaptic plasticity to determine network structure. PMID:26291697

Deficient plasticity in the primary visual cortex of alpha-calcium/calmodulin-dependent protein kinase II mutant mice.

PubMed

Gordon, J A; Cioffi, D; Silva, A J; Stryker, M P

1996-09-01

The recent characterization of plasticity in the mouse visual cortex permits the use of mutant mice to investigate the cellular mechanisms underlying activity-dependent development. As calcium-dependent signaling pathways have been implicated in neuronal plasticity, we examined visual cortical plasticity in mice lacking the alpha-isoform of calcium/calmodulin-dependent protein kinase II (alpha CaMKII). In wild-type mice, brief occlusion of vision in one eye during a critical period reduces responses in the visual cortex. In half of the alpha CaMKII-deficient mice, visual cortical responses developed normally, but visual cortical plasticity was greatly diminished. After intensive training, spatial learning in the Morris water maze was severely impaired in a similar fraction of mutant animals. These data indicate that loss of alpha CaMKII results in a severe but variable defect in neuronal plasticity.

Structural Components of Synaptic Plasticity and Memory Consolidation

PubMed Central

Bailey, Craig H.; Kandel, Eric R.; Harris, Kristen M.

2015-01-01

Consolidation of implicit memory in the invertebrate Aplysia and explicit memory in the mammalian hippocampus are associated with remodeling and growth of preexisting synapses and the formation of new synapses. Here, we compare and contrast structural components of the synaptic plasticity that underlies these two distinct forms of memory. In both cases, the structural changes involve time-dependent processes. Thus, some modifications are transient and may contribute to early formative stages of long-term memory, whereas others are more stable, longer lasting, and likely to confer persistence to memory storage. In addition, we explore the possibility that trans-synaptic signaling mechanisms governing de novo synapse formation during development can be reused in the adult for the purposes of structural synaptic plasticity and memory storage. Finally, we discuss how these mechanisms set in motion structural rearrangements that prepare a synapse to strengthen the same memory and, perhaps, to allow it to take part in other memories as a basis for understanding how their anatomical representation results in the enhanced expression and storage of memories in the brain. PMID:26134321

A History of Spike-Timing-Dependent Plasticity

PubMed Central

Markram, Henry; Gerstner, Wulfram; Sjöström, Per Jesper

2011-01-01

How learning and memory is achieved in the brain is a central question in neuroscience. Key to today’s research into information storage in the brain is the concept of synaptic plasticity, a notion that has been heavily influenced by Hebb's (1949) postulate. Hebb conjectured that repeatedly and persistently co-active cells should increase connective strength among populations of interconnected neurons as a means of storing a memory trace, also known as an engram. Hebb certainly was not the first to make such a conjecture, as we show in this history. Nevertheless, literally thousands of studies into the classical frequency-dependent paradigm of cellular learning rules were directly inspired by the Hebbian postulate. But in more recent years, a novel concept in cellular learning has emerged, where temporal order instead of frequency is emphasized. This new learning paradigm – known as spike-timing-dependent plasticity (STDP) – has rapidly gained tremendous interest, perhaps because of its combination of elegant simplicity, biological plausibility, and computational power. But what are the roots of today’s STDP concept? Here, we discuss several centuries of diverse thinking, beginning with philosophers such as Aristotle, Locke, and Ribot, traversing, e.g., Lugaro’s plasticità and Rosenblatt’s perceptron, and culminating with the discovery of STDP. We highlight interactions between theoretical and experimental fields, showing how discoveries sometimes occurred in parallel, seemingly without much knowledge of the other field, and sometimes via concrete back-and-forth communication. We point out where the future directions may lie, which includes interneuron STDP, the functional impact of STDP, its mechanisms and its neuromodulatory regulation, and the linking of STDP to the developmental formation and continuous plasticity of neuronal networks. PMID:22007168

Crystal structures reveal metal-binding plasticity at the metallo-β-lactamase active site of PqqB from Pseudomonas putida

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tu, Xiongying; Latham, John A.; Klema, Valerie J.

PqqB is an enzyme involved in the biosynthesis of pyrroloquinoline quinone and a distal member of the metallo-β-lactamase (MBL) superfamily. PqqB lacks two residues in the conserved signature motif HxHxDH that makes up the key metal-chelating elements that can bind up to two metal ions at the active site of MBLs and other members of its superfamily. Here, we report crystal structures of PqqB bound to Mn2+, Mg2+, Cu2+, and Zn2+. These structures demonstrate that PqqB can still bind metal ions at the canonical MBL active site. The fact that PqqB can adapt its side chains to chelate a widemore » spectrum of metal ions with different coordination features on a uniform main chain scaffold demonstrates its metal-binding plasticity. This plasticity may provide insights into the structural basis of promiscuous activities found in ensembles of metal complexes within this superfamily. Furthermore, PqqB belongs to a small subclass of MBLs that contain an additional CxCxxC motif that binds a structural Zn2+. Our data support a key role for this motif in dimerization.« less

Ubiquitous and temperature-dependent neural plasticity in hibernators.

PubMed

von der Ohe, Christina G; Darian-Smith, Corinna; Garner, Craig C; Heller, H Craig

2006-10-11

Hibernating mammals are remarkable for surviving near-freezing brain temperatures and near cessation of neural activity for a week or more at a time. This extreme physiological state is associated with dendritic and synaptic changes in hippocampal neurons. Here, we investigate whether these changes are a ubiquitous phenomenon throughout the brain that is driven by temperature. We iontophoretically injected Lucifer yellow into several types of neurons in fixed slices from hibernating ground squirrels. We analyzed neuronal microstructure from animals at several stages of torpor at two different ambient temperatures, and during the summer. We show that neuronal cell bodies, dendrites, and spines from several cell types in hibernating ground squirrels retract on entry into torpor, change little over the course of several days, and then regrow during the 2 h return to euthermia. Similar structural changes take place in neurons from the hippocampus, cortex, and thalamus, suggesting a global phenomenon. Investigation of neural microstructure from groups of animals hibernating at different ambient temperatures revealed that there is a linear relationship between neural retraction and minimum body temperature. Despite significant temperature-dependent differences in extent of retraction during torpor, recovery reaches the same final values of cell body area, dendritic arbor complexity, and spine density. This study demonstrates large-scale and seemingly ubiquitous neural plasticity in the ground squirrel brain during torpor. It also defines a temperature-driven model of dramatic neural plasticity, which provides a unique opportunity to explore mechanisms of large-scale regrowth in adult mammals, and the effects of remodeling on learning and memory.

Multiscale Modeling of Structurally-Graded Materials Using Discrete Dislocation Plasticity Models and Continuum Crystal Plasticity Models

NASA Technical Reports Server (NTRS)

Saether, Erik; Hochhalter, Jacob D.; Glaessgen, Edward H.

2012-01-01

A multiscale modeling methodology that combines the predictive capability of discrete dislocation plasticity and the computational efficiency of continuum crystal plasticity is developed. Single crystal configurations of different grain sizes modeled with periodic boundary conditions are analyzed using discrete dislocation plasticity (DD) to obtain grain size-dependent stress-strain predictions. These relationships are mapped into crystal plasticity parameters to develop a multiscale DD/CP model for continuum level simulations. A polycrystal model of a structurally-graded microstructure is developed, analyzed and used as a benchmark for comparison between the multiscale DD/CP model and the DD predictions. The multiscale DD/CP model follows the DD predictions closely up to an initial peak stress and then follows a strain hardening path that is parallel but somewhat offset from the DD predictions. The difference is believed to be from a combination of the strain rate in the DD simulation and the inability of the DD/CP model to represent non-monotonic material response.

Origin of the spike-timing-dependent plasticity rule

NASA Astrophysics Data System (ADS)

Cho, Myoung Won; Choi, M. Y.

2016-08-01

A biological synapse changes its efficacy depending on the difference between pre- and post-synaptic spike timings. Formulating spike-timing-dependent interactions in terms of the path integral, we establish a neural-network model, which makes it possible to predict relevant quantities rigorously by means of standard methods in statistical mechanics and field theory. In particular, the biological synaptic plasticity rule is shown to emerge as the optimal form for minimizing the free energy. It is further revealed that maximization of the entropy of neural activities gives rise to the competitive behavior of biological learning. This demonstrates that statistical mechanics helps to understand rigorously key characteristic behaviors of a neural network, thus providing the possibility of physics serving as a useful and relevant framework for probing life.

Activity-Dependent Downscaling of Subthreshold Synaptic Inputs during Slow-Wave-Sleep-like Activity In Vivo.

PubMed

González-Rueda, Ana; Pedrosa, Victor; Feord, Rachael C; Clopath, Claudia; Paulsen, Ole

2018-03-21

Activity-dependent synaptic plasticity is critical for cortical circuit refinement. The synaptic homeostasis hypothesis suggests that synaptic connections are strengthened during wake and downscaled during sleep; however, it is not obvious how the same plasticity rules could explain both outcomes. Using whole-cell recordings and optogenetic stimulation of presynaptic input in urethane-anesthetized mice, which exhibit slow-wave-sleep (SWS)-like activity, we show that synaptic plasticity rules are gated by cortical dynamics in vivo. While Down states support conventional spike timing-dependent plasticity, Up states are biased toward depression such that presynaptic stimulation alone leads to synaptic depression, while connections contributing to postsynaptic spiking are protected against this synaptic weakening. We find that this novel activity-dependent and input-specific downscaling mechanism has two important computational advantages: (1) improved signal-to-noise ratio, and (2) preservation of previously stored information. Thus, these synaptic plasticity rules provide an attractive mechanism for SWS-related synaptic downscaling and circuit refinement. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

CREB at the Crossroads of Activity-Dependent Regulation of Nervous System Development and Function.

PubMed

Belgacem, Yesser H; Borodinsky, Laura N

2017-01-01

The central nervous system is a highly plastic network of cells that constantly adjusts its functions to environmental stimuli throughout life. Transcription-dependent mechanisms modify neuronal properties to respond to external stimuli regulating numerous developmental functions, such as cell survival and differentiation, and physiological functions such as learning, memory, and circadian rhythmicity. The discovery and cloning of the cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB) constituted a big step toward deciphering the molecular mechanisms underlying neuronal plasticity. CREB was first discovered in learning and memory studies as a crucial mediator of activity-dependent changes in target gene expression that in turn impose long-lasting modifications of the structure and function of neurons. In this chapter, we review the molecular and signaling mechanisms of neural activity-dependent recruitment of CREB and its cofactors. We discuss the crosstalk between signaling pathways that imprints diverse spatiotemporal patterns of CREB activation allowing for the integration of a wide variety of stimuli.

Experience-dependent plasticity in white matter microstructure: reasoning training alters structural connectivity

PubMed Central

Mackey, Allyson P.; Whitaker, Kirstie J.; Bunge, Silvia A.

2012-01-01

Diffusion tensor imaging (DTI) techniques have made it possible to investigate white matter plasticity in humans. Changes in DTI measures, principally increases in fractional anisotropy (FA), have been observed following training programs as diverse as juggling, meditation, and working memory. Here, we sought to test whether three months of reasoning training could alter white matter microstructure. We recruited participants (n = 23) who were enrolled in a course to prepare for the Law School Admission Test (LSAT), a test that places strong demands on reasoning skills, as well as age- and IQ-matched controls planning to take the LSAT in the future (n = 22). DTI data were collected at two scan sessions scheduled three months apart. In trained participants but not controls, we observed decreases in radial diffusivity (RD) in white matter connecting frontal cortices, and in mean diffusivity (MD) within frontal and parietal lobe white matter. Further, participants exhibiting larger gains on the LSAT exhibited greater decreases in MD in the right internal capsule. In summary, reasoning training altered multiple measures of white matter structure in young adults. While the cellular underpinnings are unknown, these results provide evidence of experience-dependent white matter changes that may not be limited to myelination. PMID:22936899

A model of activity-dependent changes in dendritic spine density and spine structure.

PubMed

Crook, S M; Dur-E-Ahmad, M; Baer, S M

2007-10-01

Recent evidence indicates that the morphology and density of dendritic spines are regulated during synaptic plasticity. See, for instance, a review by Hayashi and Majewska [9]. In this work, we extend previous modeling studies [27] by combining a model for activity-dependent spine density with one for calcium-mediated spine stem restructuring. The model is based on the standard dimensionless cable equation, which represents the change in the membrane potential in a passive dendrite. Additional equations characterize the change in spine density along the dendrite, the current balance equation for an individual spine head, the change in calcium concentration in the spine head, and the dynamics of spine stem resistance. We use computational studies to investigate the changes in spine density and structure for differing synaptic inputs and demonstrate the effects of these changes on the input-output properties of the dendritic branch. Moderate amounts of high-frequency synaptic activation to dendritic spines result in an increase in spine stem resistance that is correlated with spine stem elongation. In addition, the spine density increases both inside and outside the input region. The model is formulated so that this long-term potentiation-inducing stimulus eventually leads to structural stability. In contrast, a prolonged low-frequency stimulation paradigm that would typically induce long-term depression results in a decrease in stem resistance (correlated with stem shortening) and an eventual decrease in spine density.

Neuromodulatory influence of norepinephrine during developmental experience-dependent plasticity.

PubMed

Golovin, Randall M; Ward, Nicholas J

2016-07-01

Critical periods represent phases of development during which neuronal circuits and their responses can be readily shaped by stimuli. Experience-dependent plasticity that occurs within these critical periods can be influenced in many ways; however, Shepard et al. (J Neurosci 35: 2432-2437, 2015) recently singled out norepinephrine as an essential driver of this plasticity within the auditory cortex. This work provides novel insight into the mechanisms of critical period plasticity and challenges previous conceptions that a functional redundancy exists between noradrenergic and cholinergic influences on cortical plasticity. Copyright © 2016 the American Physiological Society.

Structural plasticity mediates distinct GAP-dependent GTP hydrolysis mechanisms in Rab33 and Rab5.

PubMed

Majumdar, Soneya; Acharya, Abhishek; Prakash, Balaji

2017-12-01

The classical GTP hydrolysis mechanism, as seen in Ras, employs a catalytic glutamine provided in cis by the GTPase and an arginine supplied in trans by a GTPase activating protein (GAP). The key idea emergent from a large body of research on small GTPases is that GTPases employ a variety of different hydrolysis mechanisms; evidently, these variations permit diverse rates of GTPase inactivation, crucial for temporal regulation of different biological processes. Recently, we unified these variations and argued that a steric clash between active site residues (corresponding to positions 12 and 61 of Ras) governs whether a GTPase utilizes the cis-Gln or the trans-Gln (from the GAP) for catalysis. As the cis-Gln encounters a steric clash, the Rab GTPases employ the so-called dual finger mechanism where the interacting GAP supplies a trans-Gln for catalysis. Using experimental and computational methods, we demonstrate how the cis-Gln of Rab33 overcomes the steric clash when it is stabilized by a residue in the vicinity. In effect, this demonstrates how both cis-Gln- and trans-Gln-mediated mechanisms could operate in the same GTPase in different contexts, i.e. depending on the GAP that regulates its action. Interestingly, in the case of Rab5, which possesses a higher intrinsic GTP hydrolysis rate, a similar stabilization of the cis-Gln appears to overcome the steric clash. Taken together with the mechanisms seen for Rab1, it is evident that the observed variations in Rab and their GAP partners allow structural plasticity, or in other words, the choice of different catalytic mechanisms. © 2017 Federation of European Biochemical Societies.

Gamma-band activation predicts both associative memory and cortical plasticity

PubMed Central

Headley, Drew B.; Weinberger, Norman M.

2011-01-01

Gamma-band oscillations are a ubiquitous phenomenon in the nervous system and have been implicated in multiple aspects of cognition. In particular, the strength of gamma oscillations at the time a stimulus is encoded predicts its subsequent retrieval, suggesting that gamma may reflect enhanced mnemonic processing. Likewise, activity in the gamma-band can modulate plasticity in vitro. However, it is unclear whether experience-dependent plasticity in vivo is also related to gamma-band activation. The aim of the present study is to determine whether gamma activation in primary auditory cortex modulates both the associative memory for an auditory stimulus during classical conditioning and its accompanying specific receptive field plasticity. Rats received multiple daily sessions of single tone/shock trace and two-tone discrimination conditioning, during which local field potentials and multiunit discharges were recorded from chronically implanted electrodes. We found that the strength of tone-induced gamma predicted the acquisition of associative memory 24 h later, and ceased to predict subsequent performance once asymptote was reached. Gamma activation also predicted receptive field plasticity that specifically enhanced representation of the signal tone. This concordance provides a long-sought link between gamma oscillations, cortical plasticity and the formation of new memories. PMID:21900554

Categorizing experience-based foraging plasticity in mites: age dependency, primacy effects and memory persistence

PubMed Central

Davaasambuu, Undarmaa; Saussure, Stéphanie; Christiansen, Inga C.

2018-01-01

Behavioural plasticity can be categorized into activational (also termed contextual) and developmental plasticity. Activational plasticity allows immediate contextual behavioural changes, whereas developmental plasticity is characterized by time-lagged changes based on memory of previous experiences (learning). Behavioural plasticity tends to decline with age but whether this holds true for both plasticity categories and the effects of first-in-life experiences is poorly understood. We tackled this issue by assessing the foraging plasticity of plant-inhabiting predatory mites, Amblyseius swirskii, on thrips and spider mites following age-dependent prey experience, i.e. after hatching or after reaching maturity. Juvenile and young adult predator females were alternately presented thrips and spider mites, for establishing 1st and 2nd prey-in-life experiences, and tested, as gravid females, for their foraging plasticity when offered both prey species. Prey experience by juvenile predators resulted in clear learning effects, which were evident in likelier and earlier attacks on familiar prey, and higher proportional inclusion of familiar prey in total diet. First prey-in-life experience by juvenile but not adult predators resulted in primacy effects regarding attack latency. Prey experience by adult predators resulted mainly in prey-unspecific physiological changes, with easy-to-grasp spider mites providing higher net energy gains than difficult-to-grasp thrips. Prey experience by juvenile, but not adult, predators was adaptive, which was evident in a negative correlation between attack latencies and egg production. Overall, our study provides key evidence that similar experiences by juvenile and adult predators, including first-in-life experiences, may be associated with different types of behavioural plasticity, i.e. developmental and activational plasticity. PMID:29765663

Categorizing experience-based foraging plasticity in mites: age dependency, primacy effects and memory persistence.

PubMed

Schausberger, Peter; Davaasambuu, Undarmaa; Saussure, Stéphanie; Christiansen, Inga C

2018-04-01

Behavioural plasticity can be categorized into activational (also termed contextual) and developmental plasticity. Activational plasticity allows immediate contextual behavioural changes, whereas developmental plasticity is characterized by time-lagged changes based on memory of previous experiences (learning). Behavioural plasticity tends to decline with age but whether this holds true for both plasticity categories and the effects of first-in-life experiences is poorly understood. We tackled this issue by assessing the foraging plasticity of plant-inhabiting predatory mites, Amblyseius swirskii , on thrips and spider mites following age-dependent prey experience, i.e. after hatching or after reaching maturity. Juvenile and young adult predator females were alternately presented thrips and spider mites, for establishing 1st and 2nd prey-in-life experiences, and tested, as gravid females, for their foraging plasticity when offered both prey species. Prey experience by juvenile predators resulted in clear learning effects, which were evident in likelier and earlier attacks on familiar prey, and higher proportional inclusion of familiar prey in total diet. First prey-in-life experience by juvenile but not adult predators resulted in primacy effects regarding attack latency. Prey experience by adult predators resulted mainly in prey-unspecific physiological changes, with easy-to-grasp spider mites providing higher net energy gains than difficult-to-grasp thrips. Prey experience by juvenile, but not adult, predators was adaptive, which was evident in a negative correlation between attack latencies and egg production. Overall, our study provides key evidence that similar experiences by juvenile and adult predators, including first-in-life experiences, may be associated with different types of behavioural plasticity, i.e. developmental and activational plasticity.

Hierarchical structure and physicochemical properties of plasticized chitosan.

PubMed

Meng, Qingkai; Heuzey, Marie-Claude; Carreau, Pierre J

2014-04-14

Plasticized chitosan with hierarchical structure, including multiple length scale structural units, was prepared by a "melt"-based method, that is, thermomechanical mixing, as opposed to the usual casting-evaporation procedure. Chitosan was successfully plasticized by thermomechanical mixing in the presence of concentrated lactic acid and glycerol using a batch mixer. Different plasticization formulations were compared in this study, in which concentrated lactic acid was used as protonation agent as well as plasticizer. The microstructure of thermomechanically plasticized chitosan was investigated by X-ray diffraction, scanning electron microscopy, and optical microscopy. With increasing amount of additional plasticizers (glycerol or water), the crystallinity of the plasticized chitosan decreased from 63.7% for the original chitosan powder to almost zero for the sample plasticized with additional water. Salt linkage between lactic acid molecules and amino side chains of chitosan was confirmed by FTIR spectroscopy: the lactic acid molecules expanded the space between the chitosan molecules of the crystalline phase. In the presence of other plasticizers (glycerol and water), various levels of structural units including an amorphous phase, nanofibrils, nanofibril clusters, and microfibers were produced under mechanical shear and thermal energy and identified for the first time. The thermal and thermomechanical properties of the plasticized chitosan were measured by thermogravimetric analysis, differential scanning calorimetric, and DMA. These properties were correlated with the different levels of microstructure, including multiple structural units.

Postsynaptic density 95 (PSD-95) serine 561 phosphorylation regulates a conformational switch and bidirectional dendritic spine structural plasticity.

PubMed

Wu, Qian; Sun, Miao; Bernard, Laura P; Zhang, Huaye

2017-09-29

Postsynaptic density 95 (PSD-95) is a major synaptic scaffolding protein that plays a key role in bidirectional synaptic plasticity, which is a process important for learning and memory. It is known that PSD-95 shows increased dynamics upon induction of plasticity. However, the underlying structural and functional changes in PSD-95 that mediate its role in plasticity remain unclear. Here we show that phosphorylation of PSD-95 at Ser-561 in its guanylate kinase (GK) domain, which is mediated by the partitioning-defective 1 (Par1) kinases, regulates a conformational switch and is important for bidirectional plasticity. Using a fluorescence resonance energy transfer (FRET) biosensor, we show that a phosphomimetic mutation of Ser-561 promotes an intramolecular interaction between GK and the nearby Src homology 3 (SH3) domain, leading to a closed conformation, whereas a non-phosphorylatable S561A mutation or inhibition of Par1 kinase activity decreases SH3-GK interaction, causing PSD-95 to adopt an open conformation. In addition, S561A mutation facilitates the interaction between PSD-95 and its binding partners. Fluorescence recovery after photobleaching imaging reveals that the S561A mutant shows increased stability, whereas the phosphomimetic S561D mutation increases PSD-95 dynamics at the synapse. Moreover, molecular replacement of endogenous PSD-95 with the S561A mutant blocks dendritic spine structural plasticity during chemical long-term potentiation and long-term depression. Endogenous Ser-561 phosphorylation is induced by synaptic NMDA receptor activation, and the SH3-GK domains exhibit a Ser-561 phosphorylation-dependent switch to a closed conformation during synaptic plasticity. Our results provide novel mechanistic insight into the regulation of PSD-95 in dendritic spine structural plasticity through phosphorylation-mediated regulation of protein dynamics and conformation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Myelin Associated Inhibitors: A Link Between Injury-Induced and Experience-Dependent Plasticity

PubMed Central

Akbik, Feras; Cafferty, William B. J.; Strittmatter, Stephen M.

2011-01-01

SUMMARY In the adult, both neurologic recovery and anatomical growth after a CNS injury are limited. Two classes of growth inhibitors, myelin associated inhibitors (MAIs) and extracellular matrix associated inhibitors, limit both functional recovery and anatomical rearrangements in animal models of spinal cord injury. Here we focus on how MAIs limit a wide spectrum of growth that includes regeneration, sprouting, and plasticity in both the intact and lesioned CNS. Three classic myelin associated inhibitors, Nogo-A, MAG, and OMgp, signal through their common receptors, Nogo-66 Receptor-1 (NgR1) and Paired-Immunoglobulin-like-Receptor-1 (PirB), to regulate cytoskeletal dynamics and inhibit growth. Initially described as inhibitors of axonal regeneration, subsequent work has demonstrated that MAIs also limit activity and experience-dependent plasticity in the intact, adult CNS. MAIs therefore represent a point of convergence for plasticity that limits anatomical rearrangements regardless of the inciting stimulus, blurring the distinction between injury studies and more “basic” plasticity studies. PMID:21699896

Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage.

PubMed

Pavlopoulos, Elias; Trifilieff, Pierre; Chevaleyre, Vivien; Fioriti, Luana; Zairis, Sakellarios; Pagano, Andrew; Malleret, Gaël; Kandel, Eric R

2011-12-09

The cytoplasmic polyadenylation element-binding protein 3 (CPEB3), a regulator of local protein synthesis, is the mouse homolog of ApCPEB, a functional prion protein in Aplysia. Here, we provide evidence that CPEB3 is activated by Neuralized1, an E3 ubiquitin ligase. In hippocampal cultures, CPEB3 activated by Neuralized1-mediated ubiquitination leads both to the growth of new dendritic spines and to an increase of the GluA1 and GluA2 subunits of AMPA receptors, two CPEB3 targets essential for synaptic plasticity. Conditional overexpression of Neuralized1 similarly increases GluA1 and GluA2 and the number of spines and functional synapses in the hippocampus and is reflected in enhanced hippocampal-dependent memory and synaptic plasticity. By contrast, inhibition of Neuralized1 reduces GluA1 and GluA2 levels and impairs hippocampal-dependent memory and synaptic plasticity. These results suggest a model whereby Neuralized1-dependent ubiquitination facilitates hippocampal plasticity and hippocampal-dependent memory storage by modulating the activity of CPEB3 and CPEB3-dependent protein synthesis and synapse formation. Copyright © 2011 Elsevier Inc. All rights reserved.

Neuronal plasticity and neurotrophic factors in drug responses

PubMed Central

Castrén, Eero; Antila, Hanna

2017-01-01

Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks. Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors. Several clinically available drugs directly activate neurotrophins and neuronal plasticity. In particular, antidepressant drugs rapidly activate TrkB signaling and gradually increase BDNF expression, and the behavioral effects of antidepressants are mediated by and dependent on BDNF signaling through TrkB at least in rodents. These findings indicate that antidepressants, widely used drugs, effectively act as TrkB activators. They further imply that neuronal plasticity is a central mechanism in the action of antidepressant drugs. Indeed, it was recently discovered that antidepressants reactivate a state of plasticity in the adult cerebral cortex that closely resembles the enhanced plasticity normally observed during postnatal critical periods. This state of induced plasticity, known as iPlasticity, allows environmental stimuli to beneficially reorganize networks abnormally wired during early life. iPlasticity has been observed in cortical as well as subcortical networks and is induced by several pharmacological and non-pharmacological treatments. iPlasticity is a new pharmacological principle where drug treatment and rehabilitation cooperate: the drug acts permissively to enhance plasticity and rehabilitation provides activity to guide the appropriate wiring of the plastic network. Optimization of iPlastic drug treatment with novel means of rehabilitation may help improve the efficacy of available drug treatments and expand the use of

Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways

PubMed Central

Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

2015-01-01

Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses. PMID:26241953

Activity-Dependent Bidirectional Regulation of GAD Expression in a Homeostatic Fashion Is Mediated by BDNF-Dependent and Independent Pathways.

PubMed

Hanno-Iijima, Yoko; Tanaka, Masami; Iijima, Takatoshi

2015-01-01

Homeostatic synaptic plasticity, or synaptic scaling, is a mechanism that tunes neuronal transmission to compensate for prolonged, excessive changes in neuronal activity. Both excitatory and inhibitory neurons undergo homeostatic changes based on synaptic transmission strength, which could effectively contribute to a fine-tuning of circuit activity. However, gene regulation that underlies homeostatic synaptic plasticity in GABAergic (GABA, gamma aminobutyric) neurons is still poorly understood. The present study demonstrated activity-dependent dynamic scaling in which NMDA-R (N-methyl-D-aspartic acid receptor) activity regulated the expression of GABA synthetic enzymes: glutamic acid decarboxylase 65 and 67 (GAD65 and GAD67). Results revealed that activity-regulated BDNF (brain-derived neurotrophic factor) release is necessary, but not sufficient, for activity-dependent up-scaling of these GAD isoforms. Bidirectional forms of activity-dependent GAD expression require both BDNF-dependent and BDNF-independent pathways, both triggered by NMDA-R activity. Additional results indicated that these two GAD genes differ in their responsiveness to chronic changes in neuronal activity, which could be partially caused by differential dependence on BDNF. In parallel to activity-dependent bidirectional scaling in GAD expression, the present study further observed that a chronic change in neuronal activity leads to an alteration in neurotransmitter release from GABAergic neurons in a homeostatic, bidirectional fashion. Therefore, the differential expression of GAD65 and 67 during prolonged changes in neuronal activity may be implicated in some aspects of bidirectional homeostatic plasticity within mature GABAergic presynapses.

Drosophila Fragile X Mental Retardation Protein Developmentally Regulates Activity-Dependent Axon Pruning

PubMed Central

Tessier, Charles R.; Broadie, Kendal

2014-01-01

Summary Fragile X Syndrome (FraX) is a broad-spectrum neurological disorder with symptoms ranging from hyperexcitability to mental retardation and autism. Loss of the fragile X mental retardation 1 (fmr1) gene product, the mRNA-binding translational regulator FMRP, causes structural over-elaboration of dendritic and axonal processes as well as functional alterations in synaptic plasticity at maturity. It is unclear, however, whether FraX is primarily a disease of development, a disease of plasticity or both; a distinction vital for engineering intervention strategies. To address this critical issue, we have used the Drosophila FraX model to investigate the developmental roles of Drosophila FMRP (dFMRP). dFMRP expression and regulation of chickadee/profilin coincides with a transient window of late brain development. During this time, dFMRP is positively regulated by sensory input activity, and required to limit axon growth and for efficient activity-dependent pruning of axon branches in the Mushroom Body learning/memory center. These results demonstrate that dFMRP has a primary role in activity-dependent neural circuit refinement in late brain development. PMID:18321984

Generalized continuum modeling of scale-dependent crystalline plasticity

NASA Astrophysics Data System (ADS)

Mayeur, Jason R.

The use of metallic material systems (e.g. pure metals, alloys, metal matrix composites) in a wide range of engineering applications from medical devices to electronic components to automobiles continues to motivate the development of improved constitutive models to meet increased performance demands while minimizing cost. Emerging technologies often incorporate materials in which the dominant microstructural features have characteristic dimensions reaching into the submicron and nanometer regime. Metals comprised of such fine microstructures often exhibit unique and size-dependent mechanical response, and classical approaches to constitutive model development at engineering (continuum) scales, being local in nature, are inadequate for describing such behavior. Therefore, traditional modeling frameworks must be augmented and/or reformulated to account for such phenomena. Crystal plasticity constitutive models have proven quite capable of capturing first-order microstructural effects such as grain orientation (elastic/plastic anisotropy), grain morphology, phase distribution, etc. on the deformation behavior of both single and polycrystals, yet suffer from the same limitations as other local continuum theories with regard to capturing scale-dependent mechanical response. This research is focused on the development, numerical implementation, and application of a generalized (nonlocal) theory of single crystal plasticity capable of describing the scale-dependent mechanical response of both single and polycrystalline metals that arises as a result of heterogeneous deformation. This research developed a dislocation-based theory of micropolar single crystal plasticity. The majority of nonlocal crystal plasticity theories are predicated on the connection between gradients of slip and geometrically necessary dislocations. Due to the diversity of existing nonlocal crystal plasticity theories, a review, summary, and comparison of representative model classes is presented in

Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

PubMed Central

Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

2015-01-01

Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

Two Coincidence Detectors for Spike Timing-Dependent Plasticity in Somatosensory Cortex

PubMed Central

Bender, Vanessa A.; Bender, Kevin J.; Brasier, Daniel J.; Feldman, Daniel E.

2011-01-01

Many cortical synapses exhibit spike timing-dependent plasticity (STDP) in which the precise timing of presynaptic and postsynaptic spikes induces synaptic strengthening [long-term potentiation (LTP)] or weakening [long-term depression (LTD)]. Standard models posit a single, postsynaptic, NMDA receptor-based coincidence detector for LTP and LTD components of STDP. We show instead that STDP at layer 4 to layer 2/3 synapses in somatosensory (S1) cortex involves separate calcium sources and coincidence detection mechanisms for LTP and LTD. LTP showed classical NMDA receptor dependence. LTD was independent of postsynaptic NMDA receptors and instead required group I metabotropic glutamate receptors and calcium from voltage-sensitive channels and IP3 receptor-gated stores. Downstream of postsynaptic calcium, LTD required retrograde endocannabinoid signaling, leading to presynaptic LTD expression, and also required activation of apparently presynaptic NMDA receptors. These LTP and LTD mechanisms detected firing coincidence on ~25 and ~125 ms time scales, respectively, and combined to implement the overall STDP rule. These findings indicate that STDP is not a unitary process and suggest that endocannabinoid-dependent LTD may be relevant to cortical map plasticity. PMID:16624937

The dependence of granular plasticity on particle shape

NASA Astrophysics Data System (ADS)

Murphy, Kieran; Jaeger, Heinrich

Granular materials plastically deform through reworking an intricate network of particle-particle contacts. Some particle rearrangements have only a fleeting effect before being forgotten while others set in motion global restructuring. How particle shape affects local interactions and how those, in turn, influence the nature of the aggregate's plasticity is far from clear, especially in three dimensions. Here we investigate the remarkably wide range of behaviors in the yielding regime, from quiescent flow to violent jerks, depending on particle shape. We study this complex dependence via uniaxial compression experiments on aggregates of 3D-printed particles, and complement stress-strain data with simultaneous x-ray videos and volumetric strain measurements. We find power law distributions of the slip magnitudes, and discuss their universality. Our data show that the multitude of small slips serves to gradually dilate the packing whereas the fewer large ones accompany significant compaction events. Our findings provide new insights into general features of granular materials during plastic deformation and highlight how small changes in particle shape can give rise to drastic differences in yielding behavior.

Functional Evolution of PLP-dependent Enzymes based on Active-Site Structural Similarities

PubMed Central

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-01-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5’-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the Comparison of Protein Active Site Structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. PMID:24920327

Spike-timing-dependent plasticity in the human dorso-lateral prefrontal cortex.

PubMed

Casula, Elias Paolo; Pellicciari, Maria Concetta; Picazio, Silvia; Caltagirone, Carlo; Koch, Giacomo

2016-12-01

Changes in the synaptic strength of neural connections are induced by repeated coupling of activity of interconnected neurons with precise timing, a phenomenon known as spike-timing-dependent plasticity (STDP). It is debated if this mechanism exists in large-scale cortical networks in humans. We combined transcranial magnetic stimulation (TMS) with concurrent electroencephalography (EEG) to directly investigate the effects of two paired associative stimulation (PAS) protocols (fronto-parietal and parieto-frontal) of pre and post-synaptic inputs within the human fronto-parietal network. We found evidence that the dorsolateral prefrontal cortex (DLPFC) has the potential to form robust STDP. Long-term potentiation/depression of TMS-evoked cortical activity is prompted after that DLPFC stimulation is followed/preceded by posterior parietal stimulation. Such bidirectional changes are paralleled by sustained increase/decrease of high-frequency oscillatory activity, likely reflecting STDP responsivity. The current findings could be important to drive plasticity of damaged cortical circuits in patients with cognitive or psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Experience-Dependent Synaptic Plasticity in V1 Occurs without Microglial CX3CR1

PubMed Central

Stevens, Beth

2017-01-01

Brief monocular deprivation (MD) shifts ocular dominance and reduces the density of thalamic synapses in layer 4 of the mouse primary visual cortex (V1). We found that microglial lysosome content is also increased as a result of MD. Previous studies have shown that the microglial fractalkine receptor CX3CR1 is involved in synaptic development and hippocampal plasticity. We therefore tested the hypothesis that neuron-to-microglial communication via CX3CR1 is an essential component of visual cortical development and plasticity in male mice. Our data show that CX3CR1 is not required for normal development of V1 responses to visual stimulation, multiple forms of experience-dependent plasticity, or the synapse loss that accompanies MD in layer 4. By ruling out an essential role for fractalkine signaling, our study narrows the search for understanding how microglia respond to active synapse modification in the visual cortex. SIGNIFICANCE STATEMENT Microglia in the visual cortex respond to monocular deprivation with increased lysosome content, but signaling through the fractalkine receptor CX3CR1 is not an essential component in the mechanisms of visual cortical development or experience-dependent synaptic plasticity. PMID:28951447

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

PubMed

Butz, Markus; Steenbuck, Ines D; van Ooyen, Arjen

2014-01-01

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, while deafferentated neurons increased their betweenness centrality as they rewired and returned to the homeostatic range of activity. Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons. Together, our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair.

Functional evolution of PLP-dependent enzymes based on active-site structural similarities.

PubMed

Catazaro, Jonathan; Caprez, Adam; Guru, Ashu; Swanson, David; Powers, Robert

2014-10-01

Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS. © 2014 Wiley Periodicals, Inc.

Studies on the effect of storage time and plasticizers on the structural variations in thermoplastic starch.

PubMed

Schmitt, H; Guidez, A; Prashantha, K; Soulestin, J; Lacrampe, M F; Krawczak, P

2015-01-22

Starch was combined with plasticizers such as glycerol, sorbitol, glycerol/sorbitol and urea/ethanolamine blends by means of high shear extrusion process to prepare thermoplastic starch (TPS). Effect of storage time and plasticizers on the structural stability of melt processed TPS was investigated. Morphological observation, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy reveal that melt extrusion process is efficient in transforming granular starch into a plasticized starch for all plasticizer compositions. XRD analysis highlights major changes in the microstructure of plasticized starch, and dependence of crystalline type and degree of crystallinity mainly on the plasticizer composition and storage time. Dynamical mechanical analysis (DMA) yields a decrease of the peak intensity of loss factor with aging time. The effect of ageing on tensile strength also appears to be highly dependent on the plasticizer composition. Thus, through different plasticizer combinations and ageing, starch-based materials with significant differences in tensile properties can be obtained, which may be tuned to meet the requirements of a wide range of applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Learning complex temporal patterns with resource-dependent spike timing-dependent plasticity.

PubMed

Hunzinger, Jason F; Chan, Victor H; Froemke, Robert C

2012-07-01

Studies of spike timing-dependent plasticity (STDP) have revealed that long-term changes in the strength of a synapse may be modulated substantially by temporal relationships between multiple presynaptic and postsynaptic spikes. Whereas long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength have been modeled as distinct or separate functional mechanisms, here, we propose a new shared resource model. A functional consequence of our model is fast, stable, and diverse unsupervised learning of temporal multispike patterns with a biologically consistent spiking neural network. Due to interdependencies between LTP and LTD, dendritic delays, and proactive homeostatic aspects of the model, neurons are equipped to learn to decode temporally coded information within spike bursts. Moreover, neurons learn spike timing with few exposures in substantial noise and jitter. Surprisingly, despite having only one parameter, the model also accurately predicts in vitro observations of STDP in more complex multispike trains, as well as rate-dependent effects. We discuss candidate commonalities in natural long-term plasticity mechanisms.

Hebbian Wiring Plasticity Generates Efficient Network Structures for Robust Inference with Synaptic Weight Plasticity

PubMed Central

Hiratani, Naoki; Fukai, Tomoki

2016-01-01

In the adult mammalian cortex, a small fraction of spines are created and eliminated every day, and the resultant synaptic connection structure is highly nonrandom, even in local circuits. However, it remains unknown whether a particular synaptic connection structure is functionally advantageous in local circuits, and why creation and elimination of synaptic connections is necessary in addition to rich synaptic weight plasticity. To answer these questions, we studied an inference task model through theoretical and numerical analyses. We demonstrate that a robustly beneficial network structure naturally emerges by combining Hebbian-type synaptic weight plasticity and wiring plasticity. Especially in a sparsely connected network, wiring plasticity achieves reliable computation by enabling efficient information transmission. Furthermore, the proposed rule reproduces experimental observed correlation between spine dynamics and task performance. PMID:27303271

Plasticity of Neuron-Glial Transmission: Equipping Glia for Long-Term Integration of Network Activity.

PubMed

Croft, Wayne; Dobson, Katharine L; Bellamy, Tomas C

2015-01-01

The capacity of synaptic networks to express activity-dependent changes in strength and connectivity is essential for learning and memory processes. In recent years, glial cells (most notably astrocytes) have been recognized as active participants in the modulation of synaptic transmission and synaptic plasticity, implicating these electrically nonexcitable cells in information processing in the brain. While the concept of bidirectional communication between neurons and glia and the mechanisms by which gliotransmission can modulate neuronal function are well established, less attention has been focussed on the computational potential of neuron-glial transmission itself. In particular, whether neuron-glial transmission is itself subject to activity-dependent plasticity and what the computational properties of such plasticity might be has not been explored in detail. In this review, we summarize current examples of plasticity in neuron-glial transmission, in many brain regions and neurotransmitter pathways. We argue that induction of glial plasticity typically requires repetitive neuronal firing over long time periods (minutes-hours) rather than the short-lived, stereotyped trigger typical of canonical long-term potentiation. We speculate that this equips glia with a mechanism for monitoring average firing rates in the synaptic network, which is suited to the longer term roles proposed for astrocytes in neurophysiology.

Microelectrode array recordings of cultured hippocampal networks reveal a simple model for transcription and protein synthesis-dependent plasticity.

PubMed

Arnold, Fiona J L; Hofmann, Frank; Bengtson, C Peter; Wittmann, Malte; Vanhoutte, Peter; Bading, Hilmar

2005-04-01

A simplified cell culture system was developed to study neuronal plasticity. As changes in synaptic strength may alter network activity patterns, we grew hippocampal neurones on a microelectrode array (MEA) and monitored their collective behaviour with 60 electrodes simultaneously. We found that exposure of the network for 15 min to the GABA(A) receptor antagonist bicuculline induced an increase in synaptic efficacy at excitatory synapses that was associated with an increase in the frequency of miniature AMPA receptor-mediated EPSCs and a change in network activity from uncoordinated firing of neurones (lacking any recognizable pattern) to a highly organized, periodic and synchronous burst pattern. Induction of recurrent synchronous bursting was dependent on NMDA receptor activation and required extracellular signal-regulated kinase (ERK)1/2 signalling and translation of pre-existing mRNAs. Once induced, the burst pattern persisted for several days; its maintenance phase (> 4 h) was dependent on gene transcription taking place in a critical period of 120 min following induction. Thus, cultured hippocampal neurones display a simple, transcription and protein synthesis-dependent form of plasticity. The non-invasive nature of MEA recordings provides a significant advantage over traditional assays for synaptic connectivity (i.e. long-term potentiation in brain slices) and facilitates the search for activity-regulated genes critical for late-phase plasticity.

Cognitive plasticity as a moderator of functional dependency in elderly patients hospitalized for bone fractures.

PubMed

Calero-García, M J; Calero, M D; Navarro, E; Ortega, A R

2015-01-01

Bone fractures in older adults involve hospitalization and surgical intervention, aspects that have been related to loss of autonomy and independence. Several variables have been studied as moderators of how these patients recover. However, the implications of cognitive plasticity for functional recovery have not been studied to date. The present study analyzes the relationship between cognitive plasticity--defined as the capacity for learning or improved performance under conditions of training or performance optimization--and functional recovery in older adults hospitalized following a bone fracture. The study comprised 165 older adults who underwent surgery for bone fractures at a hospital in southern Spain. Participants were evaluated at different time points thereafter, with instruments that measure activities of daily life (ADL), namely the Barthel Index (BI) and the Lawton Index, as well as with a learning potential (cognitive plasticity) assessment test (Auditory Verbal Learning Test of Learning Potential, AVLT-LP). Results show that most of the participants have improved their level of independence 3 months after the intervention. However, some patients continue to have medium to high levels of dependency and this dependency is related to cognitive plasticity. The results of this study reveal the importance of the cognitive plasticity variable for evaluating older adults hospitalized for a fracture. They indicate a possible benefit to be obtained by implementing programs that reduce the degree of long-term dependency or decrease the likelihood of it arising.

Spike-timing dependent plasticity in primate corticospinal connections induced during free behavior

PubMed Central

Nishimura, Yukio; Perlmutter, Steve I.; Eaton, Ryan W.; Fetz, Eberhard E.

2014-01-01

Motor learning and functional recovery from brain damage involve changes in the strength of synaptic connections between neurons. Relevant in vivo evidence on the underlying cellular mechanisms remains limited and indirect. We found that the strength of neural connections between motor cortex and spinal cord in monkeys can be modified with an autonomous recurrent neural interface that delivers electrical stimuli in the spinal cord triggered by action potentials of corticospinal cells during free behavior. The activity-dependent stimulation modified the strength of the terminal connections of single corticomotoneuronal cells, consistent with a bidirectional spike-timing dependent plasticity rule previously derived from in vitro experiments. For some cells the changes lasted for days after the end of conditioning, but most effects eventually reverted to preconditioning levels. These results provide the first direct evidence of corticospinal synaptic plasticity in vivo at the level of single neurons induced by normal firing patterns during free behavior. PMID:24210907

Dense-body aggregates as plastic structures supporting tension in smooth muscle cells.

PubMed

Zhang, Jie; Herrera, Ana M; Paré, Peter D; Seow, Chun Y

2010-11-01

The wall of hollow organs of vertebrates is a unique structure able to generate active tension and maintain a nearly constant passive stiffness over a large volume range. These properties are predominantly attributable to the smooth muscle cells that line the organ wall. Although smooth muscle is known to possess plasticity (i.e., the ability to adapt to large changes in cell length through structural remodeling of contractile apparatus and cytoskeleton), the detailed structural basis for the plasticity is largely unknown. Dense bodies, one of the most prominent structures in smooth muscle cells, have been regarded as the anchoring sites for actin filaments, similar to the Z-disks in striated muscle. Here, we show that the dense bodies and intermediate filaments formed cable-like structures inside airway smooth muscle cells and were able to adjust the cable length according to cell length and tension. Stretching the muscle cell bundle in the relaxed state caused the cables to straighten, indicating that these intracellular structures were connected to the extracellular matrix and could support passive tension. These plastic structures may be responsible for the ability of smooth muscle to maintain a nearly constant tensile stiffness over a large length range. The finding suggests that the structural plasticity of hollow organs may originate from the dense-body cables within the smooth muscle cells.

Plastic and Large-Deflection Analysis of Nonlinear Structures

NASA Technical Reports Server (NTRS)

Thomson, R. G.; Hayduk, R. J.; Robinson, M. P.; Durling, B. J.; Pifko, A.; Levine, H. S.; Armen, H. J.; Levy, A.; Ogilvie, P.

1982-01-01

Plastic and Large Deflection Analysis of Nonlinear Structures (PLANS) system is collection of five computer programs for finite-element static-plastic and large deflection analysis of variety of nonlinear structures. System considers bending and membrane stresses, general three-dimensional bodies, and laminated composites.

The secret life of ground squirrels: accelerometry reveals sex-dependent plasticity in above-ground activity

PubMed Central

Wilsterman, Kathryn; Zhang, Victor; Moore, Jeanette; Barnes, Brian M.; Buck, C. Loren

2016-01-01

The sexes differ in how and when they allocate energy towards reproduction, but how this influences phenotypic plasticity in daily activity patterns is unclear. Here, we use collar-mounted light loggers and triaxial accelerometers to examine factors that affect time spent above ground and overall dynamic body acceleration (ODBA), an index of activity-specific energy expenditure, across the active season of free-living, semi-fossorial arctic ground squirrels (Urocitellus parryii). We found high day-to-day variability in time spent above ground and ODBA with most of the variance explained by environmental conditions known to affect thermal exchange. In both years, females spent more time below ground compared with males during parturition and early lactation; however, this difference was fourfold larger in the second year, possibly, because females were in better body condition. Daily ODBA positively correlated with time spent above ground in both sexes, but females were more active per unit time above ground. Consequently, daily ODBA did not differ between the sexes when females were early in lactation, even though females were above ground three to six fewer hours each day. Further, on top of having the additional burden of milk production, ODBA data indicate females also had fragmented rest patterns and were more active during late lactation. Our results indicate that sex differences in reproductive requirements can have a substantial influence on activity patterns, but the size of this effect may be dependent on capital resources accrued during gestation. PMID:27703706

Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

PubMed

Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

2010-09-15

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

PubMed Central

Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

2015-01-01

Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral

Emergent spatial synaptic structure from diffusive plasticity.

PubMed

Sweeney, Yann; Clopath, Claudia

2017-04-01

Some neurotransmitters can diffuse freely across cell membranes, influencing neighbouring neurons regardless of their synaptic coupling. This provides a means of neural communication, alternative to synaptic transmission, which can influence the way in which neural networks process information. Here, we ask whether diffusive neurotransmission can also influence the structure of synaptic connectivity in a network undergoing plasticity. We propose a form of Hebbian synaptic plasticity which is mediated by a diffusive neurotransmitter. Whenever a synapse is modified at an individual neuron through our proposed mechanism, similar but smaller modifications occur in synapses connecting to neighbouring neurons. The effects of this diffusive plasticity are explored in networks of rate-based neurons. This leads to the emergence of spatial structure in the synaptic connectivity of the network. We show that this spatial structure can coexist with other forms of structure in the synaptic connectivity, such as with groups of strongly interconnected neurons that form in response to correlated external drive. Finally, we explore diffusive plasticity in a simple feedforward network model of receptive field development. We show that, as widely observed across sensory cortex, the preferred stimulus identity of neurons in our network become spatially correlated due to diffusion. Our proposed mechanism of diffusive plasticity provides an efficient mechanism for generating these spatial correlations in stimulus preference which can flexibly interact with other forms of synaptic organisation. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Nogo-A regulates spatial learning as well as memory formation and modulates structural plasticity in the adult mouse hippocampus.

PubMed

Zagrebelsky, Marta; Lonnemann, Niklas; Fricke, Steffen; Kellner, Yves; Preuß, Eike; Michaelsen-Preusse, Kristin; Korte, Martin

2017-02-01

Behavioral learning has been shown to involve changes in the function and structure of synaptic connections of the central nervous system (CNS). On the other hand, the neuronal circuitry in the mature brain is characterized by a high degree of stability possibly providing a correlate for long-term storage of information. This observation indicates the requirement for a set of molecules inhibiting plasticity and promoting stability thereby providing temporal and spatial specificity to plastic processes. Indeed, signaling of Nogo-A via its receptors has been shown to play a crucial role in restricting activity-dependent functional and structural plasticity in the adult CNS. However, whether Nogo-A controls learning and memory formation and what are the cellular and molecular mechanisms underlying this function is still unclear. Here we show that Nogo-A signaling controls spatial learning and reference memory formation upon training in the Morris water maze and negatively modulates structural changes at spines in the mouse hippocampus. Learning processes and the correlated structural plasticity have been shown to involve changes in excitatory as well as in inhibitory neuronal connections. We show here that Nogo-A is highly expressed not only in excitatory, but also in inhibitory, Parvalbumin positive neurons in the adult hippocampus. By this means our current and previous data indicate that Nogo-A loss-of-function positively influences spatial learning by priming the neuronal structure to a higher plasticity level. Taken together our results link the role of Nogo-A in negatively regulating plastic processes to a physiological function in controlling learning and memory processes in the mature hippocampus and open the interesting possibility that it might mainly act by controlling the function of the hippocampal inhibitory circuitry. Copyright © 2016 Elsevier Inc. All rights reserved.

Microelectrode array recordings of cultured hippocampal networks reveal a simple model for transcription and protein synthesis-dependent plasticity

PubMed Central

Arnold, Fiona JL; Hofmann, Frank; Bengtson, C. Peter; Wittmann, Malte; Vanhoutte, Peter; Bading, Hilmar

2005-01-01

A simplified cell culture system was developed to study neuronal plasticity. As changes in synaptic strength may alter network activity patterns, we grew hippocampal neurones on a microelectrode array (MEA) and monitored their collective behaviour with 60 electrodes simultaneously. We found that exposure of the network for 15 min to the GABAA receptor antagonist bicuculline induced an increase in synaptic efficacy at excitatory synapses that was associated with an increase in the frequency of miniature AMPA receptor-mediated EPSCs and a change in network activity from uncoordinated firing of neurones (lacking any recognizable pattern) to a highly organized, periodic and synchronous burst pattern. Induction of recurrent synchronous bursting was dependent on NMDA receptor activation and required extracellular signal-regulated kinase (ERK)1/2 signalling and translation of pre-existing mRNAs. Once induced, the burst pattern persisted for several days; its maintenance phase (> 4 h) was dependent on gene transcription taking place in a critical period of 120 min following induction. Thus, cultured hippocampal neurones display a simple, transcription and protein synthesis-dependent form of plasticity. The non-invasive nature of MEA recordings provides a significant advantage over traditional assays for synaptic connectivity (i.e. long-term potentiation in brain slices) and facilitates the search for activity-regulated genes critical for late-phase plasticity. PMID:15618268

Learning-dependent plasticity in human auditory cortex during appetitive operant conditioning.

PubMed

Puschmann, Sebastian; Brechmann, André; Thiel, Christiane M

2013-11-01

Animal experiments provide evidence that learning to associate an auditory stimulus with a reward causes representational changes in auditory cortex. However, most studies did not investigate the temporal formation of learning-dependent plasticity during the task but rather compared auditory cortex receptive fields before and after conditioning. We here present a functional magnetic resonance imaging study on learning-related plasticity in the human auditory cortex during operant appetitive conditioning. Participants had to learn to associate a specific category of frequency-modulated tones with a reward. Only participants who learned this association developed learning-dependent plasticity in left auditory cortex over the course of the experiment. No differential responses to reward predicting and nonreward predicting tones were found in auditory cortex in nonlearners. In addition, learners showed similar learning-induced differential responses to reward-predicting and nonreward-predicting tones in the ventral tegmental area and the nucleus accumbens, two core regions of the dopaminergic neurotransmitter system. This may indicate a dopaminergic influence on the formation of learning-dependent plasticity in auditory cortex, as it has been suggested by previous animal studies. Copyright © 2012 Wiley Periodicals, Inc.

Intramolecular structural model for photoinduced plasticity in chalcogenide glasses

NASA Astrophysics Data System (ADS)

Yannopoulos, S. N.

2003-08-01

Selected spectral features of Raman spectra of glassy As2S3 subjected to elongation stress and sub-band-gap light illumination are analyzed and compared with polarization-dependent information obtained from the bulk glass at room temperature and near the glass transition temperature. The data are suggestive of specific structural changes which involve the transformation of atomic arrangements from realgarlike As4S4 molecules, originally present in virgin (untreated) fibers, into planar orpimentlike clusters. Implications of these atomic rearrangements to the incipient photoinduced fluidity—the onset of plastic deformation—in As2S3 glass are discussed. Kinetics of photoinduced plastic changes is compared to that of Raman spectra changes, revealing a qualitative similar behavior. An approximate estimation of the relative contribution of intermolecular rearrangements and the intramolecular structural mechanism proposed in this paper has revealed that the latter is responsible for almost 30% of the photoinduced elongation of the fiber’s length at room temperature. The proposed mechanism can as well serve as rationale for understanding the photoinduced volume expansion observed in chalcogenide glasses.

Effects of bursting dynamic features on the generation of multi-clustered structure of neural network with symmetric spike-timing-dependent plasticity learning rule.

PubMed

Liu, Hui; Song, Yongduan; Xue, Fangzheng; Li, Xiumin

2015-11-01

In this paper, the generation of multi-clustered structure of self-organized neural network with different neuronal firing patterns, i.e., bursting or spiking, has been investigated. The initially all-to-all-connected spiking neural network or bursting neural network can be self-organized into clustered structure through the symmetric spike-timing-dependent plasticity learning for both bursting and spiking neurons. However, the time consumption of this clustering procedure of the burst-based self-organized neural network (BSON) is much shorter than the spike-based self-organized neural network (SSON). Our results show that the BSON network has more obvious small-world properties, i.e., higher clustering coefficient and smaller shortest path length than the SSON network. Also, the results of larger structure entropy and activity entropy of the BSON network demonstrate that this network has higher topological complexity and dynamical diversity, which benefits for enhancing information transmission of neural circuits. Hence, we conclude that the burst firing can significantly enhance the efficiency of clustering procedure and the emergent clustered structure renders the whole network more synchronous and therefore more sensitive to weak input. This result is further confirmed from its improved performance on stochastic resonance. Therefore, we believe that the multi-clustered neural network which self-organized from the bursting dynamics has high efficiency in information processing.

Effects of bursting dynamic features on the generation of multi-clustered structure of neural network with symmetric spike-timing-dependent plasticity learning rule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Hui; Song, Yongduan; Xue, Fangzheng

In this paper, the generation of multi-clustered structure of self-organized neural network with different neuronal firing patterns, i.e., bursting or spiking, has been investigated. The initially all-to-all-connected spiking neural network or bursting neural network can be self-organized into clustered structure through the symmetric spike-timing-dependent plasticity learning for both bursting and spiking neurons. However, the time consumption of this clustering procedure of the burst-based self-organized neural network (BSON) is much shorter than the spike-based self-organized neural network (SSON). Our results show that the BSON network has more obvious small-world properties, i.e., higher clustering coefficient and smaller shortest path length than themore » SSON network. Also, the results of larger structure entropy and activity entropy of the BSON network demonstrate that this network has higher topological complexity and dynamical diversity, which benefits for enhancing information transmission of neural circuits. Hence, we conclude that the burst firing can significantly enhance the efficiency of clustering procedure and the emergent clustered structure renders the whole network more synchronous and therefore more sensitive to weak input. This result is further confirmed from its improved performance on stochastic resonance. Therefore, we believe that the multi-clustered neural network which self-organized from the bursting dynamics has high efficiency in information processing.« less

Dependence of Plastic TATB Shock-Wave Sensitivity on Temperature, Density and Technology Factors

NASA Astrophysics Data System (ADS)

Vlasov, Yu. A.; Kosolapov, V. B.; Fomicheva, L. V.; Khabarov, I. P.

1999-06-01

Mixed TATB-based HE is the most perspective because of the manufacture and exploitation safety of its items. At the same time the safety of these explosive, at high temperatures, which take place at emergencies, causes the certain anxiety. Plastic TATB shock-wave sensitivity (SWS) researches has shown that temperature as one of the important factors of external influence is not always the determining reason of SWS change. It is known that density influence on SWS significantly. At the same time density depends on temperature and technology of details manufacturing. In this connection in this work the temperature dependence of plastic TATB SWS was studied in view of convertible and irreversible changes of density (p) under heating at -50[C up to 90[C . It is shown that during these influences the dependence of threshold pressure of initiation (P) from temperature is explained, first of all, by change of HE density, caused by its thermal expansion (compression), and also by irreversible changes of p and HE structure, arising at heating. It is found also that the share of irreversible change of density depends on technology of HE details manufacturing and is explained by relaxation of residual pressure in them. The mentioned relaxation is finished after the first cycles of thermal influence. The value of density change, caused by this factor, depends on temperature and duration of heating.

Structural defects in natural plastically deformed diamonds: Evidence from EPR spectroscopy

NASA Astrophysics Data System (ADS)

Mineeva, R. M.; Titkov, S. V.; Speransky, A. V.

2009-06-01

Structural defects formed as a result of plastic deformation in natural diamond crystals have been studied by EPR spectroscopy. The spectra of brown, pink-brown, black-brown, pink-purple, and gray plastically deformed diamonds of type Ia from deposits in Yakutia and the Urals were recorded. The results of EPR spectroscopy allowed us to identify various deformation centers in the structure of natural diamonds and to show that nitrogen centers were transformed under epigenetic mechanical loading. Abundant A centers, consisting of two isomorphic nitrogen atoms located in neighboring structural sites, were destroyed as a result of this process to form a series of N1, N4, W7, M2, and M3 nitrogen centers. Such centers are characterized by an anisotropic spatial distribution and a positive charge, related to the mechanism of their formation. In addition, N2 centers (probably, deformation-produced dislocations decorated by nitrogen) were formed in all plastically deformed diamonds and W10 and W35 centers (the models have not been finally ascertained) were formed in some of them. It has been established that diamonds with various types of deformation-induced color contain characteristic associations of these deformation centers. The diversity of associations of deformation centers indicates appreciable variations in conditions of disintegration of deep-seated rocks, transfer of diamonds to the Earth’s surface, and formation of kimberlitic deposits. Depending on the conditions of mechanical loading, the diamond crystals were plastically deformed by either dislocation gliding or mechanical twinning. Characteristic features of plastic deformation by dislocation gliding are the substantial prevalence of the N2 centers over other deformation centers and the occurrence of the high-spin W10 and W35 centers. The attributes of less frequent plastic deformation by mechanical twinning are unusual localization of the M2 centers and, in some cases, the N1 centers in microtwinned

Morphofunctional Experience-Dependent Plasticity in the Honeybee Brain

ERIC Educational Resources Information Center

Andrione, Mara; Timberlake, Benjamin F.; Vallortigara, Giorgio; Antolini, Renzo; Haase, Albrecht

2017-01-01

Repeated or prolonged exposure to an odorant without any positive or negative reinforcement produces experience-dependent plasticity, which results in habituation and latent inhibition. In the honeybee ("Apis mellifera"), it has been demonstrated that, even if the absolute neural representation of an odor in the primary olfactory center,…

Functional requirements for reward-modulated spike-timing-dependent plasticity.

PubMed

Frémaux, Nicolas; Sprekeler, Henning; Gerstner, Wulfram

2010-10-06

Recent experiments have shown that spike-timing-dependent plasticity is influenced by neuromodulation. We derive theoretical conditions for successful learning of reward-related behavior for a large class of learning rules where Hebbian synaptic plasticity is conditioned on a global modulatory factor signaling reward. We show that all learning rules in this class can be separated into a term that captures the covariance of neuronal firing and reward and a second term that presents the influence of unsupervised learning. The unsupervised term, which is, in general, detrimental for reward-based learning, can be suppressed if the neuromodulatory signal encodes the difference between the reward and the expected reward-but only if the expected reward is calculated for each task and stimulus separately. If several tasks are to be learned simultaneously, the nervous system needs an internal critic that is able to predict the expected reward for arbitrary stimuli. We show that, with a critic, reward-modulated spike-timing-dependent plasticity is capable of learning motor trajectories with a temporal resolution of tens of milliseconds. The relation to temporal difference learning, the relevance of block-based learning paradigms, and the limitations of learning with a critic are discussed.

Context-dependent plasticity in the subcortical encoding of linguistic pitch patterns

PubMed Central

Lau, Joseph C. Y.; Wong, Patrick C. M.

2016-01-01

We examined the mechanics of online experience-dependent auditory plasticity by assessing the influence of prior context on the frequency-following responses (FFRs), which reflect phase-locked responses from neural ensembles within the subcortical auditory system. FFRs were elicited to a Cantonese falling lexical pitch pattern from 24 native speakers of Cantonese in a variable context, wherein the falling pitch pattern randomly occurred in the context of two other linguistic pitch patterns; in a patterned context, wherein, the falling pitch pattern was presented in a predictable sequence along with two other pitch patterns, and in a repetitive context, wherein the falling pitch pattern was presented with 100% probability. We found that neural tracking of the stimulus pitch contour was most faithful and accurate when listening context was patterned and least faithful when the listening context was variable. The patterned context elicited more robust pitch tracking relative to the repetitive context, suggesting that context-dependent plasticity is most robust when the context is predictable but not repetitive. Our study demonstrates a robust influence of prior listening context that works to enhance online neural encoding of linguistic pitch patterns. We interpret these results as indicative of an interplay between contextual processes that are responsive to predictability as well as novelty in the presentation context. NEW & NOTEWORTHY Human auditory perception in dynamic listening environments requires fine-tuning of sensory signal based on behaviorally relevant regularities in listening context, i.e., online experience-dependent plasticity. Our finding suggests what partly underlie online experience-dependent plasticity are interplaying contextual processes in the subcortical auditory system that are responsive to predictability as well as novelty in listening context. These findings add to the literature that looks to establish the neurophysiological bases of

Context-dependent plasticity in the subcortical encoding of linguistic pitch patterns.

PubMed

Lau, Joseph C Y; Wong, Patrick C M; Chandrasekaran, Bharath

2017-02-01

We examined the mechanics of online experience-dependent auditory plasticity by assessing the influence of prior context on the frequency-following responses (FFRs), which reflect phase-locked responses from neural ensembles within the subcortical auditory system. FFRs were elicited to a Cantonese falling lexical pitch pattern from 24 native speakers of Cantonese in a variable context, wherein the falling pitch pattern randomly occurred in the context of two other linguistic pitch patterns; in a patterned context, wherein, the falling pitch pattern was presented in a predictable sequence along with two other pitch patterns, and in a repetitive context, wherein the falling pitch pattern was presented with 100% probability. We found that neural tracking of the stimulus pitch contour was most faithful and accurate when listening context was patterned and least faithful when the listening context was variable. The patterned context elicited more robust pitch tracking relative to the repetitive context, suggesting that context-dependent plasticity is most robust when the context is predictable but not repetitive. Our study demonstrates a robust influence of prior listening context that works to enhance online neural encoding of linguistic pitch patterns. We interpret these results as indicative of an interplay between contextual processes that are responsive to predictability as well as novelty in the presentation context. Human auditory perception in dynamic listening environments requires fine-tuning of sensory signal based on behaviorally relevant regularities in listening context, i.e., online experience-dependent plasticity. Our finding suggests what partly underlie online experience-dependent plasticity are interplaying contextual processes in the subcortical auditory system that are responsive to predictability as well as novelty in listening context. These findings add to the literature that looks to establish the neurophysiological bases of auditory system

Presynaptic Ionotropic Receptors Controlling and Modulating the Rules for Spike Timing-Dependent Plasticity

PubMed Central

Verhoog, Matthijs B.; Mansvelder, Huibert D.

2011-01-01

Throughout life, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. In line with predictions made by Hebb, synapse strength can be modified depending on the millisecond timing of action potential firing (STDP). The sign of synaptic plasticity depends on the spike order of presynaptic and postsynaptic neurons. Ionotropic neurotransmitter receptors, such as NMDA receptors and nicotinic acetylcholine receptors, are intimately involved in setting the rules for synaptic strengthening and weakening. In addition, timing rules for STDP within synapses are not fixed. They can be altered by activation of ionotropic receptors located at, or close to, synapses. Here, we will highlight studies that uncovered how network actions control and modulate timing rules for STDP by activating presynaptic ionotropic receptors. Furthermore, we will discuss how interaction between different types of ionotropic receptors may create “timing” windows during which particular timing rules lead to synaptic changes. PMID:21941664

Presynaptic ionotropic receptors controlling and modulating the rules for spike timing-dependent plasticity.

PubMed

Verhoog, Matthijs B; Mansvelder, Huibert D

2011-01-01

Throughout life, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. In line with predictions made by Hebb, synapse strength can be modified depending on the millisecond timing of action potential firing (STDP). The sign of synaptic plasticity depends on the spike order of presynaptic and postsynaptic neurons. Ionotropic neurotransmitter receptors, such as NMDA receptors and nicotinic acetylcholine receptors, are intimately involved in setting the rules for synaptic strengthening and weakening. In addition, timing rules for STDP within synapses are not fixed. They can be altered by activation of ionotropic receptors located at, or close to, synapses. Here, we will highlight studies that uncovered how network actions control and modulate timing rules for STDP by activating presynaptic ionotropic receptors. Furthermore, we will discuss how interaction between different types of ionotropic receptors may create "timing" windows during which particular timing rules lead to synaptic changes.

A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons.

PubMed

Kong, Dong; Dagon, Yossi; Campbell, John N; Guo, Yikun; Yang, Zongfang; Yi, Xinchi; Aryal, Pratik; Wellenstein, Kerry; Kahn, Barbara B; Sabatini, Bernardo L; Lowell, Bradford B

2016-07-06

AMP-activated protein kinase (AMPK) plays an important role in regulating food intake. The downstream AMPK substrates and neurobiological mechanisms responsible for this, however, are ill defined. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus regulate hunger. Their firing increases with fasting, and once engaged they cause feeding. AgRP neuron activity is regulated by state-dependent synaptic plasticity: fasting increases dendritic spines and excitatory synaptic activity; feeding does the opposite. The signaling mechanisms underlying this, however, are also unknown. Using neuron-specific approaches to measure and manipulate kinase activity specifically within AgRP neurons, we establish that fasting increases AMPK activity in AgRP neurons, that increased AMPK activity in AgRP neurons is both necessary and sufficient for fasting-induced spinogenesis and excitatory synaptic activity, and that the AMPK phosphorylation target mediating this plasticity is p21-activated kinase. This provides a signaling and neurobiological basis for both AMPK regulation of energy balance and AgRP neuron state-dependent plasticity. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-dependent long-term structural and functional effects of early life seizures: evidence for a hippocampal critical period influencing plasticity in adulthood

PubMed Central

Meyerand, M.E.; Sutula, T.

2015-01-01

Neural activity promotes circuit formation in developing systems and during critical periods permanently modifies circuit organization and functional properties. These observations suggest that excessive neural activity, as occurs during seizures, might influence developing neural circuitry with long-term outcomes that depend on age at the time of seizures. We systematically examined long-term structural and functional consequences of seizures induced in rats by kainic acid, pentylenetetrazol, and hyperthermia across postnatal ages from birth through postnatal day 90 in adulthood (P90). Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and electrophysiological methods at ≥P95 following seizures induced from P1 to P90 demonstrated consistent patterns of gross atrophy, microstructural abnormalities in the corpus callosum and hippocampus, and functional alterations in hippocampal circuitry at ≥P95 that were independent of the method of seizure induction and varied systematically as a function of age at the time of seizures. Three distinct epochs were observed in which seizures resulted in distinct long-term structural and functional outcomes at ≥P95. Seizures prior to P20 resulted in DTI abnormalities in corpus callosum and hippocampus in the absence of gross cerebral atrophy, and increased paired pulse inhibition (PPI) in the dentate gyrus at ≥P95. Seizures after P30 induced a different pattern of DTI abnormalities in the fimbria and hippocampus accompanied by gross cerebral atrophy with increases in lateral ventricular volume, as well as increased PPI in the dentate gyrus at ≥P95. In contrast, seizures between P20-P30 did not result in cerebral atrophy or significant imaging abnormalities in the hippocampus or white matter, but irreversibly decreased PPI in the dentate gyrus compared to normal adult controls. These age-specific long-term structural and functional outcomes identify P20-P30 as a potential critical period in hippocampal

Temperature dependence of the plastic scintillator detector for DAMPE

NASA Astrophysics Data System (ADS)

Wang, Zhao-Min; Yu, Yu-Hong; Sun, Zhi-Yu; Yue, Ke; Yan, Duo; Zhang, Yong-Jie; Zhou, Yong; Fang, Fang; Huang, Wen-Xue; Chen, Jun-Ling

2017-01-01

The Plastic Scintillator Detector (PSD) is one of the main sub-detectors in the DArk Matter Particle Explorer (DAMPE) project. It will be operated over a large temperature range from -10 to 30 °C, so the temperature effect of the whole detection system should be studied in detail. The temperature dependence of the PSD system is mainly contributed by the three parts: the plastic scintillator bar, the photomultiplier tube (PMT), and the Front End Electronics (FEE). These three parts have been studied in detail and the contribution of each part has been obtained and discussed. The temperature coefficient of the PMT is -0.320(±0.033)%/°C, and the coefficient of the plastic scintillator bar is -0.036(±0.038)%/°C. This result means that after subtracting the FEE pedestal, the variation of the signal amplitude of the PMT-scintillator system due to temperature mainly comes from the PMT, and the plastic scintillator bar is not sensitive to temperature over the operating range. Since the temperature effect cannot be ignored, the temperature dependence of the whole PSD has been also studied and a correction has been made to minimize this effect. The correction result shows that the effect of temperature on the signal amplitude of the PSD system can be suppressed. Supported by Strategic Priority Research Program on Space Science of the Chinese Academy of Sciences (XDA04040202-3) and Youth Innovation Promotion Association, CAS

Activity-Induced Synaptic Structural Modifications by an Activator of Integrin Signaling at the Drosophila Neuromuscular Junction.

PubMed

Lee, Joo Yeun; Geng, Junhua; Lee, Juhyun; Wang, Andrew R; Chang, Karen T

2017-03-22

Activity-induced synaptic structural modification is crucial for neural development and synaptic plasticity, but the molecular players involved in this process are not well defined. Here, we report that a protein named Shriveled (Shv) regulates synaptic growth and activity-dependent synaptic remodeling at the Drosophila neuromuscular junction. Depletion of Shv causes synaptic overgrowth and an accumulation of immature boutons. We find that Shv physically and genetically interacts with βPS integrin. Furthermore, Shv is secreted during intense, but not mild, neuronal activity to acutely activate integrin signaling, induce synaptic bouton enlargement, and increase postsynaptic glutamate receptor abundance. Consequently, loss of Shv prevents activity-induced synapse maturation and abolishes post-tetanic potentiation, a form of synaptic plasticity. Our data identify Shv as a novel trans-synaptic signal secreted upon intense neuronal activity to promote synapse remodeling through integrin receptor signaling. SIGNIFICANCE STATEMENT The ability of neurons to rapidly modify synaptic structure in response to neuronal activity, a process called activity-induced structural remodeling, is crucial for neuronal development and complex brain functions. The molecular players that are important for this fundamental biological process are not well understood. Here we show that the Shriveled (Shv) protein is required during development to maintain normal synaptic growth. We further demonstrate that Shv is selectively released during intense neuronal activity, but not mild neuronal activity, to acutely activate integrin signaling and trigger structural modifications at the Drosophila neuromuscular junction. This work identifies Shv as a key modulator of activity-induced structural remodeling and suggests that neurons use distinct molecular cues to differentially modulate synaptic growth and remodeling to meet synaptic demand. Copyright © 2017 the authors 0270-6474/17/373246-18$15.00/0.

Evaluation of engineering plastic for rollover protective structure (ROPS) mounting.

PubMed

Comer, R S; Ayers, P D; Liu, J

2007-04-01

Agriculture has one of the highest fatality rates of any industry in America. Tractor rollovers are a significant contributor to the high death rate. Rollover protective structures (ROPS) have helped lower these high fatality rates on full-size tractors. However, a large number of older tractors still do not use ROPS due to the difficulty of designing and creating a mounting structure. To help reduce this difficulty, engineering plastics were evaluated for use in a ROPS mounting structure on older tractors. The use of engineering plastics around axle housings could provide a uniform mounting configuration as well as lower costs for aftermarket ROPS. Various plastics were examined through shear testing, scale model testing, and compressive strength testing. Once a material was chosen based upon strength and cost, full-scale testing of the plastic's strength on axle housings was conducted. Finally, a mounting structure was tested in static ROPS tests, and field upset tests were performed in accordance with SAE Standard J2194. Initial tests revealed that the ROPS mounting structure and axle housing combination had higher torsional strength with less twisting than the axle housing alone. An engineering plastic ROPS mounting structure was easily successful in withstanding the forces applied during the static longitudinal and lateral ROPS tests. Field upset testing revealed that the mounting structure could withstand the impact loads seen during actual upsets without a failure. During both static testing and field upset testing, no permanent twisting of the mounting structure was found. Engineering plastic could therefore be a viable option for a universal ROPS mounting structure for older tractors.

Somato-dendritic Synaptic Plasticity and Error-backpropagation in Active Dendrites

PubMed Central

Schiess, Mathieu; Urbanczik, Robert; Senn, Walter

2016-01-01

In the last decade dendrites of cortical neurons have been shown to nonlinearly combine synaptic inputs by evoking local dendritic spikes. It has been suggested that these nonlinearities raise the computational power of a single neuron, making it comparable to a 2-layer network of point neurons. But how these nonlinearities can be incorporated into the synaptic plasticity to optimally support learning remains unclear. We present a theoretically derived synaptic plasticity rule for supervised and reinforcement learning that depends on the timing of the presynaptic, the dendritic and the postsynaptic spikes. For supervised learning, the rule can be seen as a biological version of the classical error-backpropagation algorithm applied to the dendritic case. When modulated by a delayed reward signal, the same plasticity is shown to maximize the expected reward in reinforcement learning for various coding scenarios. Our framework makes specific experimental predictions and highlights the unique advantage of active dendrites for implementing powerful synaptic plasticity rules that have access to downstream information via backpropagation of action potentials. PMID:26841235

Effects of plasticization and shear stress on phase structure development and properties of soy protein blends.

PubMed

Chen, Feng; Zhang, Jinwen

2010-11-01

In this study, soy protein concentrate (SPC) was used as a plastic component to blend with poly(butylene adipate-co-terephthalate) (PBAT). Effects of SPC plasticization and blend composition on its deformation during mixing were studied in detail. Influence of using water as the major plasticizer and glycerol as the co-plasticizer on the deformation of the SPC phase during mixing was explored. The effect of shear stress, as affected by SPC loading level, on the phase structure of SPC in the blends was also investigated. Quantitative analysis of the aspect ratio of SPC particles was conducted by using ImageJ software, and an empirical model predicting the formation of percolated structure was applied. The experimental results and the model prediction showed a fairly good agreement. The experimental results and statistic analysis suggest that both SPC loading level and its water content prior to compounding had significant influences on development of the SPC phase structure and were correlated in determining the morphological structures of the resulting blends. Consequently, physical and mechanical properties of the blends greatly depended on the phase morphology and PBAT/SPC ratio of the blends.

Age-Dependent Glutamate Induction of Synaptic Plasticity in Cultured Hippocampal Neurons

ERIC Educational Resources Information Center

Ivenshitz, Miriam; Segal, Menahem; Sapoznik, Stav

2006-01-01

A common denominator for the induction of morphological and functional plasticity in cultured hippocampal neurons involves the activation of excitatory synapses. We now demonstrate massive morphological plasticity in mature cultured hippocampal neurons caused by a brief exposure to glutamate. This plasticity involves a slow, 70%-80% increase in…

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity.

PubMed

Chéreau, Ronan; Saraceno, G Ezequiel; Angibaud, Julie; Cattaert, Daniel; Nägerl, U Valentin

2017-02-07

Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.

Critical neural networks with short- and long-term plasticity.

PubMed

Michiels van Kessenich, L; Luković, M; de Arcangelis, L; Herrmann, H J

2018-03-01

In recent years self organized critical neuronal models have provided insights regarding the origin of the experimentally observed avalanching behavior of neuronal systems. It has been shown that dynamical synapses, as a form of short-term plasticity, can cause critical neuronal dynamics. Whereas long-term plasticity, such as Hebbian or activity dependent plasticity, have a crucial role in shaping the network structure and endowing neural systems with learning abilities. In this work we provide a model which combines both plasticity mechanisms, acting on two different time scales. The measured avalanche statistics are compatible with experimental results for both the avalanche size and duration distribution with biologically observed percentages of inhibitory neurons. The time series of neuronal activity exhibits temporal bursts leading to 1/f decay in the power spectrum. The presence of long-term plasticity gives the system the ability to learn binary rules such as xor, providing the foundation of future research on more complicated tasks such as pattern recognition.

Critical neural networks with short- and long-term plasticity

NASA Astrophysics Data System (ADS)

Michiels van Kessenich, L.; Luković, M.; de Arcangelis, L.; Herrmann, H. J.

2018-03-01

In recent years self organized critical neuronal models have provided insights regarding the origin of the experimentally observed avalanching behavior of neuronal systems. It has been shown that dynamical synapses, as a form of short-term plasticity, can cause critical neuronal dynamics. Whereas long-term plasticity, such as Hebbian or activity dependent plasticity, have a crucial role in shaping the network structure and endowing neural systems with learning abilities. In this work we provide a model which combines both plasticity mechanisms, acting on two different time scales. The measured avalanche statistics are compatible with experimental results for both the avalanche size and duration distribution with biologically observed percentages of inhibitory neurons. The time series of neuronal activity exhibits temporal bursts leading to 1 /f decay in the power spectrum. The presence of long-term plasticity gives the system the ability to learn binary rules such as xor, providing the foundation of future research on more complicated tasks such as pattern recognition.

An elastic-plastic contact model for line contact structures

NASA Astrophysics Data System (ADS)

Zhu, Haibin; Zhao, Yingtao; He, Zhifeng; Zhang, Ruinan; Ma, Shaopeng

2018-06-01

Although numerical simulation tools are now very powerful, the development of analytical models is very important for the prediction of the mechanical behaviour of line contact structures for deeply understanding contact problems and engineering applications. For the line contact structures widely used in the engineering field, few analytical models are available for predicting the mechanical behaviour when the structures deform plastically, as the classic Hertz's theory would be invalid. Thus, the present study proposed an elastic-plastic model for line contact structures based on the understanding of the yield mechanism. A mathematical expression describing the global relationship between load history and contact width evolution of line contact structures was obtained. The proposed model was verified through an actual line contact test and a corresponding numerical simulation. The results confirmed that this model can be used to accurately predict the elastic-plastic mechanical behaviour of a line contact structure.

Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

PubMed

Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

2012-01-01

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

Temperature-dependent plastic hysteresis in highly confined polycrystalline Nb films

NASA Astrophysics Data System (ADS)

Waheed, S.; Hao, R.; Zheng, Z.; Wheeler, J. M.; Michler, J.; Balint, D. S.; Giuliani, F.

2018-02-01

In this study, the effect of temperature on the cyclic deformation behaviour of a confined polycrystalline Nb film is investigated. Micropillars encapsulating a thin niobium interlayer are deformed under cyclic axial compression at different test temperatures. A distinct plastic hysteresis is observed for samples tested at elevated temperatures, whereas negligible plastic hysteresis is observed for samples tested at room temperature. These results are interpreted using planar discrete dislocation plasticity incorporating slip transmission across grain boundaries. The effect of temperature-dependent grain boundary energy and dislocation mobility on dislocation penetration and, consequently, the size of plastic hysteresis is simulated to correlate with the experimental results. It is found that the decrease in grain boundary energy barrier caused by the increase in temperature does not lead to any appreciable change in the cyclic response. However, dislocation mobility significantly affects the size of plastic hysteresis, with high mobilities leading to a larger hysteresis. Therefore, it is postulated that the experimental observations are predominantly caused by an increase in dislocation mobility as the temperature is increased above the critical temperature of body-centred cubic niobium.

Crash simulation of hybrid structures considering the stress and strain rate dependent material behavior of thermoplastic materials

NASA Astrophysics Data System (ADS)

Hopmann, Ch.; Schöngart, M.; Weber, M.; Klein, J.

2015-05-01

Thermoplastic materials are more and more used as a light weight replacement for metal, especially in the automotive industry. Since these materials do not provide the mechanical properties, which are required to manufacture supporting elements like an auto body or a cross bearer, plastics are combined with metals in so called hybrid structures. Normally, the plastics components are joined to the metal structures using different technologies like welding or screwing. Very often, the hybrid structures are made of flat metal parts, which are stiffened by a reinforcement structure made of thermoplastic materials. The loads on these structures are very often impulsive, for example in the crash situation of an automobile. Due to the large stiffness variation of metal and thermoplastic materials, complex states of stress and very high local strain rates occur in the contact zone under impact conditions. Since the mechanical behavior of thermoplastic materials is highly dependent on these types of load, the crash failure of metal plastic hybrid parts is very complex. The problem is that the normally used strain rate dependent elastic/plastic material models are not capable to simulate the mechanical behavior of thermoplastic materials depended on the state of stress. As part of a research project, a method to simulate the mechanical behavior of hybrid structures under impact conditions is developed at the IKV. For this purpose, a specimen for the measurement of mechanical properties dependet on the state of stress and a method for the strain rate depended characterization of thermoplastic materials were developed. In the second step impact testing is performed. A hybrid structure made from a metal sheet and a reinforcement structure of a Polybutylenterephthalat Polycarbonate blend is tested under impact conditions. The measured stress and strain rate depended material data are used to simulate the mechanical behavior of the hybrid structure under highly dynamic load with

[Structural plasticity associated with drugs addiction].

PubMed

Zhu, Jie; Cao, Guo-fen; Dang, Yong-hui; Chen, Teng

2011-12-01

An essential feature of drug addiction is that an individual continues to use drug despite the threat of severely adverse physical or psychosocial consequences. Persistent changes in behavior and psychological function that occur as a function of drugs of abuse are thought to be due to the reorganization of synaptic connections (structural plasticity) in relevant brain circuits (especially the brains reward circuits). In this paper we summarized evidence that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produced persistent changes in the structure of dendrites and dendritic spines on cells in relevant brain regions. We also approached the potential molecular mechanisms of these changes. It is suggested that structural plasticity associated with exposure to drugs of abuse reflects a reorganization of patterns of synaptic connectivity in these neural systems, a reorganization that alters their operation, thus contributing to some of the persistent sequela associated with drug use-including addiction.

Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice.

PubMed

Zhao, Yunan; Wang, Zhongli; Dai, Jianguo; Chen, Lin; Huang, Yufang; Zhan, Zhen

2012-03-17

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

Alpha6-Containing Nicotinic Acetylcholine Receptors Mediate Nicotine-Induced Structural Plasticity in Mouse and Human iPSC-Derived Dopaminergic Neurons.

PubMed

Collo, Ginetta; Cavalleri, Laura; Zoli, Michele; Maskos, Uwe; Ratti, Emiliangelo; Merlo Pich, Emilio

2018-01-01

Midbrain dopamine (DA) neurons are considered a critical substrate for the reinforcing and sensitizing effects of nicotine and tobacco dependence. While the role of the α4 and β2 subunit containing nicotinic acetylcholine receptors (α4β2 ∗ nAChRs) in mediating nicotine effects on DA release and DA neuron activity has been widely explored, less information is available on their role in the morphological adaptation of the DA system to nicotine, eventually leading to dysfunctional behaviors observed in nicotine dependence. In particular, no information is available on the role of α6 ∗ nAChRs in nicotine-induced structural plasticity in rodents and no direct evidence exists regarding the occurrence of structural plasticity in human DA neurons exposed to nicotine. To approach this problem, we used two parallel in vitro systems, mouse primary DA neuron cultures from E12.5 embryos and human DA neurons differentiated from induced pluripotent stem cells (iPSCs) of healthy donors, identified using TH + immunoreactivity. In both systems, nicotine 1-10 μM produced a dose-dependent increase of maximal dendrite length, number of primary dendrites, and soma size when measured after 3 days in culture. These effects were blocked by pretreatments with the α6 ∗ nAChR antagonists α-conotoxin MII and α-conotoxin PIA, as well as by the α4β2nAChR antagonist dihydro-β-erythroidine (DHβE) in both mouse and human DA neurons. Nicotine was also ineffective when the primary DA neurons were obtained from null mutant mice for either the α6 subunit or both the α4 and α6 subunits of nAChR. When pregnant mice were exposed to nicotine from gestational day 15, structural plasticity was also observed in the midbrain DA neurons of postnatal day 1 offspring only in wild-type mice and not in both null mutant mice. This study confirmed the critical role of α4α6 ∗ nAChRs in mediating nicotine-induced structural plasticity in both mouse and human DA neurons, supporting the

Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.

PubMed

Keck, Tara; Lillis, Kyle P; Zhou, Yu-Dong; White, John A

2008-07-16

Previous studies have demonstrated the presence of functional glycine receptors (GlyRs) in hippocampus. In this work, we examine the baseline activity and activity-dependent modulation of GlyRs in region CA1. We find that strychnine-sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting conductance is independent of the presynaptic stimulation rate; however, pairs of presynaptic and postsynaptic action potentials, repeated at frequencies above 5 Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to levels at least 20% larger than those seen with presynaptic stimulation alone. We refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine application, suggesting that a reduction in the number or sensitivity of membrane-inserted GlyRs underlies RDE. By extending the RDE induction protocol to include 500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic depression (LTD). Manipulations that lead to reduced functionality of GlyRs, either pharmacologically or through RDE, also lead to increased LTD. This result suggests that RDE contributes to long-term synaptic plasticity in the hippocampus.

Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood

PubMed Central

Levy, Aaron D.; Omar, Mitchell H.; Koleske, Anthony J.

2014-01-01

Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer’s disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults. PMID:25368556

The effects of hormones and physical exercise on hippocampal structural plasticity.

PubMed

Triviño-Paredes, Juan; Patten, Anna R; Gil-Mohapel, Joana; Christie, Brian R

2016-04-01

The hippocampus plays an integral role in certain aspects of cognition. Hippocampal structural plasticity and in particular adult hippocampal neurogenesis can be influenced by several intrinsic and extrinsic factors. Here we review how hormones (i.e., intrinsic modulators) and physical exercise (i.e., an extrinsic modulator) can differentially modulate hippocampal plasticity in general and adult hippocampal neurogenesis in particular. Specifically, we provide an overview of the effects of sex hormones, stress hormones, and metabolic hormones on hippocampal structural plasticity and adult hippocampal neurogenesis. In addition, we also discuss how physical exercise modulates these forms of hippocampal plasticity, giving particular emphasis on how this modulation can be affected by variables such as exercise regime, duration, and intensity. Understanding the neurobiological mechanisms underlying the modulation of hippocampal structural plasticity by intrinsic and extrinsic factors will impact the design of new therapeutic approaches aimed at restoring hippocampal plasticity following brain injury or neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Learning to learn – intrinsic plasticity as a metaplasticity mechanism for memory formation

PubMed Central

Sehgal, Megha; Song, Chenghui; Ehlers, Vanessa L.; Moyer, James R.

2013-01-01

“Use it or lose it” is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder. With the advancing age of our population, understanding how use-dependent plasticity changes across the lifespan may also help to promote healthy brain aging. A common misconception is that such experience-dependent plasticity (e.g., associative learning) is synonymous with synaptic plasticity. Other forms of plasticity also play a critical role in shaping adaptive changes within the nervous system, including intrinsic plasticity – a change in the intrinsic excitability of a neuron. Intrinsic plasticity can result from a change in the number, distribution or activity of various ion channels located throughout the neuron. Here, we review evidence that intrinsic plasticity is an important and evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts as a metaplasticity mechanism by lowering the threshold for synaptic changes. Thus, learning-related intrinsic changes can facilitate future synaptic plasticity and learning. Such intrinsic changes can impact the allocation of a memory trace within a brain structure, and when compromised, can contribute to cognitive decline during the aging process. This unique role of intrinsic excitability can provide insight into how memories are formed and, more interestingly, how neurons that participate in a memory trace are selected. Most importantly, modulation of intrinsic excitability can allow for regulation of learning ability – this can prevent or provide treatment for cognitive decline not only in patients with clinical

Neural plasticity and its initiating conditions in tinnitus.

PubMed

Roberts, L E

2018-03-01

Deafferentation caused by cochlear pathology (which can be hidden from the audiogram) activates forms of neural plasticity in auditory pathways, generating tinnitus and its associated conditions including hyperacusis. This article discusses tinnitus mechanisms and suggests how these mechanisms may relate to those involved in normal auditory information processing. Research findings from animal models of tinnitus and from electromagnetic imaging of tinnitus patients are reviewed which pertain to the role of deafferentation and neural plasticity in tinnitus and hyperacusis. Auditory neurons compensate for deafferentation by increasing their input/output functions (gain) at multiple levels of the auditory system. Forms of homeostatic plasticity are believed to be responsible for this neural change, which increases the spontaneous and driven activity of neurons in central auditory structures in animals expressing behavioral evidence of tinnitus. Another tinnitus correlate, increased neural synchrony among the affected neurons, is forged by spike-timing-dependent neural plasticity in auditory pathways. Slow oscillations generated by bursting thalamic neurons verified in tinnitus animals appear to modulate neural plasticity in the cortex, integrating tinnitus neural activity with information in brain regions supporting memory, emotion, and consciousness which exhibit increased metabolic activity in tinnitus patients. The latter process may be induced by transient auditory events in normal processing but it persists in tinnitus, driven by phantom signals from the auditory pathway. Several tinnitus therapies attempt to suppress tinnitus through plasticity, but repeated sessions will likely be needed to prevent tinnitus activity from returning owing to deafferentation as its initiating condition.

Matrix metalloproteinase-9 involvement in the structural plasticity of dendritic spines

PubMed Central

Stawarski, Michal; Stefaniuk, Marzena; Wlodarczyk, Jakub

2014-01-01

Dendritic spines are the locus for excitatory synaptic transmission in the brain and thus play a major role in neuronal plasticity. The ability to alter synaptic connections includes volumetric changes in dendritic spines that are driven by scaffolds created by the extracellular matrix (ECM). Here, we review the effects of the proteolytic activity of ECM proteases in physiological and pathological structural plasticity. We use matrix metalloproteinase-9 (MMP-9) as an example of an ECM modifier that has recently emerged as a key molecule in regulating the morphology and dysmorphology of dendritic spines that underlie synaptic plasticity and neurological disorders, respectively. We summarize the influence of MMP-9 on the dynamic remodeling of the ECM via the cleavage of extracellular substrates. We discuss its role in the formation, modification, and maintenance of dendritic spines in learning and memory. Finally, we review research that implicates MMP-9 in aberrant synaptic plasticity and spine dysmorphology in neurological disorders, with a focus on morphological abnormalities of dendritic protrusions that are associated with epilepsy. PMID:25071472

Sleep and protein synthesis-dependent synaptic plasticity: impacts of sleep loss and stress

PubMed Central

Grønli, Janne; Soulé, Jonathan; Bramham, Clive R.

2014-01-01

Sleep has been ascribed a critical role in cognitive functioning. Several lines of evidence implicate sleep in the consolidation of synaptic plasticity and long-term memory. Stress disrupts sleep while impairing synaptic plasticity and cognitive performance. Here, we discuss evidence linking sleep to mechanisms of protein synthesis-dependent synaptic plasticity and synaptic scaling. We then consider how disruption of sleep by acute and chronic stress may impair these mechanisms and degrade sleep function. PMID:24478645

Age-Dependent Ocular Dominance Plasticity in Adult Mice

PubMed Central

Lehmann, Konrad; Löwel, Siegrid

2008-01-01

Background Short monocular deprivation (4 days) induces a shift in the ocular dominance of binocular neurons in the juvenile mouse visual cortex but is ineffective in adults. Recently, it has been shown that an ocular dominance shift can still be elicited in young adults (around 90 days of age) by longer periods of deprivation (7 days). Whether the same is true also for fully mature animals is not yet known. Methodology/Principal Findings We therefore studied the effects of different periods of monocular deprivation (4, 7, 14 days) on ocular dominance in C57Bl/6 mice of different ages (25 days, 90–100 days, 109–158 days, 208–230 days) using optical imaging of intrinsic signals. In addition, we used a virtual optomotor system to monitor visual acuity of the open eye in the same animals during deprivation. We observed that ocular dominance plasticity after 7 days of monocular deprivation was pronounced in young adult mice (90–100 days) but significantly weaker already in the next age group (109–158 days). In animals older than 208 days, ocular dominance plasticity was absent even after 14 days of monocular deprivation. Visual acuity of the open eye increased in all age groups, but this interocular plasticity also declined with age, although to a much lesser degree than the optically detected ocular dominance shift. Conclusions/Significance These data indicate that there is an age-dependence of both ocular dominance plasticity and the enhancement of vision after monocular deprivation in mice: ocular dominance plasticity in binocular visual cortex is most pronounced in young animals, reduced but present in adolescence and absent in fully mature animals older than 110 days of age. Mice are thus not basically different in ocular dominance plasticity from cats and monkeys which is an absolutely essential prerequisite for their use as valid model systems of human visual disorders. PMID:18769674

Active listening: task-dependent plasticity of spectrotemporal receptive fields in primary auditory cortex.

PubMed

Fritz, Jonathan; Elhilali, Mounya; Shamma, Shihab

2005-08-01

Listening is an active process in which attentive focus on salient acoustic features in auditory tasks can influence receptive field properties of cortical neurons. Recent studies showing rapid task-related changes in neuronal spectrotemporal receptive fields (STRFs) in primary auditory cortex of the behaving ferret are reviewed in the context of current research on cortical plasticity. Ferrets were trained on spectral tasks, including tone detection and two-tone discrimination, and on temporal tasks, including gap detection and click-rate discrimination. STRF changes could be measured on-line during task performance and occurred within minutes of task onset. During spectral tasks, there were specific spectral changes (enhanced response to tonal target frequency in tone detection and discrimination, suppressed response to tonal reference frequency in tone discrimination). However, only in the temporal tasks, the STRF was changed along the temporal dimension by sharpening temporal dynamics. In ferrets trained on multiple tasks, distinctive and task-specific STRF changes could be observed in the same cortical neurons in successive behavioral sessions. These results suggest that rapid task-related plasticity is an ongoing process that occurs at a network and single unit level as the animal switches between different tasks and dynamically adapts cortical STRFs in response to changing acoustic demands.

Multi-layer network utilizing rewarded spike time dependent plasticity to learn a foraging task

PubMed Central

2017-01-01

Neural networks with a single plastic layer employing reward modulated spike time dependent plasticity (STDP) are capable of learning simple foraging tasks. Here we demonstrate advanced pattern discrimination and continuous learning in a network of spiking neurons with multiple plastic layers. The network utilized both reward modulated and non-reward modulated STDP and implemented multiple mechanisms for homeostatic regulation of synaptic efficacy, including heterosynaptic plasticity, gain control, output balancing, activity normalization of rewarded STDP and hard limits on synaptic strength. We found that addition of a hidden layer of neurons employing non-rewarded STDP created neurons that responded to the specific combinations of inputs and thus performed basic classification of the input patterns. When combined with a following layer of neurons implementing rewarded STDP, the network was able to learn, despite the absence of labeled training data, discrimination between rewarding patterns and the patterns designated as punishing. Synaptic noise allowed for trial-and-error learning that helped to identify the goal-oriented strategies which were effective in task solving. The study predicts a critical set of properties of the spiking neuronal network with STDP that was sufficient to solve a complex foraging task involving pattern classification and decision making. PMID:28961245

Training-Dependent Associative Learning Induced Neocortical Structural Plasticity: A Trace Eyeblink Conditioning Analysis

PubMed Central

Chau, Lily S.; Prakapenka, Alesia V.; Zendeli, Liridon; Davis, Ashley S.; Galvez, Roberto

2014-01-01

Studies utilizing general learning and memory tasks have suggested the importance of neocortical structural plasticity for memory consolidation. However, these learning tasks typically result in learning of multiple different tasks over several days of training, making it difficult to determine the synaptic time course mediating each learning event. The current study used trace-eyeblink conditioning to determine the time course for neocortical spine modification during learning. With eyeblink conditioning, subjects are presented with a neutral, conditioned stimulus (CS) paired with a salient, unconditioned stimulus (US) to elicit an unconditioned response (UR). With multiple CS-US pairings, subjects learn to associate the CS with the US and exhibit a conditioned response (CR) when presented with the CS. Trace conditioning is when there is a stimulus free interval between the CS and the US. Utilizing trace-eyeblink conditioning with whisker stimulation as the CS (whisker-trace-eyeblink: WTEB), previous findings have shown that primary somatosensory (barrel) cortex is required for both acquisition and retention of the trace-association. Additionally, prior findings demonstrated that WTEB acquisition results in an expansion of the cytochrome oxidase whisker representation and synaptic modification in layer IV of barrel cortex. To further explore these findings and determine the time course for neocortical learning-induced spine modification, the present study utilized WTEB conditioning to examine Golgi-Cox stained neurons in layer IV of barrel cortex. Findings from this study demonstrated a training-dependent spine proliferation in layer IV of barrel cortex during trace associative learning. Furthermore, findings from this study showing that filopodia-like spines exhibited a similar pattern to the overall spine density further suggests that reorganization of synaptic contacts set the foundation for learning-induced neocortical modifications through the different

ADP-ribosylation Factor 6 (ARF6) Bidirectionally Regulates Dendritic Spine Formation Depending on Neuronal Maturation and Activity*

PubMed Central

Kim, Yoonju; Lee, Sang-Eun; Park, Joohyun; Kim, Minhyung; Lee, Boyoon; Hwang, Daehee; Chang, Sunghoe

2015-01-01

Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increased the spine formation in developing neurons, whereas it decreased spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite patterns of expression of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via the phospholipase D pathway is the coincident factor in both stages, but the antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using tetrodotoxin or enhancing the activity in mature neurons using picrotoxin or chemical long term potentiation reversed the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons. PMID:25605715

Spike-Timing Dependent Plasticity in Unipolar Silicon Oxide RRAM Devices

PubMed Central

Zarudnyi, Konstantin; Mehonic, Adnan; Montesi, Luca; Buckwell, Mark; Hudziak, Stephen; Kenyon, Anthony J.

2018-01-01

Resistance switching, or Resistive RAM (RRAM) devices show considerable potential for application in hardware spiking neural networks (neuro-inspired computing) by mimicking some of the behavior of biological synapses, and hence enabling non-von Neumann computer architectures. Spike-timing dependent plasticity (STDP) is one such behavior, and one example of several classes of plasticity that are being examined with the aim of finding suitable algorithms for application in many computing tasks such as coincidence detection, classification and image recognition. In previous work we have demonstrated that the neuromorphic capabilities of silicon-rich silicon oxide (SiOx) resistance switching devices extend beyond plasticity to include thresholding, spiking, and integration. We previously demonstrated such behaviors in devices operated in the unipolar mode, opening up the question of whether we could add plasticity to the list of features exhibited by our devices. Here we demonstrate clear STDP in unipolar devices. Significantly, we show that the response of our devices is broadly similar to that of biological synapses. This work further reinforces the potential of simple two-terminal RRAM devices to mimic neuronal functionality in hardware spiking neural networks. PMID:29472837

Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process

PubMed Central

Walker, Brendan M.

2013-01-01

This article represents one of five contributions focusing on the topic “Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure” that were developed by awardees participating in the Young Investigator Award Symposium at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms. PMID:22459874

Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood

PubMed Central

Huang, Lianyan; Yang, Guang

2014-01-01

Background Recent studies in rodents suggest that repeated and prolonged anesthetic exposure at early stages of development leads to cognitive and behavioral impairments later in life. However, the underlying mechanism remains unknown. In this study, we tested whether exposure to general anesthesia during early development will disrupt the maturation of synaptic circuits and compromise learning-related synaptic plasticity later in life. Methods Mice received ketamine/xylazine (20/3 mg/kg) anesthesia for one or three times, starting at either early [postnatal day 14 (P14)] or late (P21) stages of development (n=105). Control mice received saline injections (n=34). At P30, mice were subjected to rotarod motor training and fear conditioning. Motor learning-induced synaptic remodeling was examined in vivo by repeatedly imaging fluorescently-labeled postsynaptic dendritic spines in the primary motor cortex before and after training using two-photon microscopy. Results Three exposures to ketamine/xylazine anesthesia between P14–18 impair the animals’ motor learning and learning-dependent dendritic spine plasticity [new spine formation, 8.4 ± 1.3% (mean ± SD) versus 13.4 ± 1.8%, P = 0.002] without affecting fear memory and cell apoptosis. One exposure at P14 or three exposures between P21–25 has no effects on the animals’ motor learning or spine plasticity. Finally, enriched motor experience ameliorates anesthesia-induced motor learning impairment and synaptic deficits. Conclusion Our study demonstrates that repeated exposures to ketamine/xylazine during early development impair motor learning and learning-dependent dendritic spine plasticity later in life. The reduction in synaptic structural plasticity may underlie anesthesia-induced behavioral impairment. PMID:25575163

A computer program for cyclic plasticity and structural fatigue analysis

NASA Technical Reports Server (NTRS)

Kalev, I.

1980-01-01

A computerized tool for the analysis of time independent cyclic plasticity structural response, life to crack initiation prediction, and crack growth rate prediction for metallic materials is described. Three analytical items are combined: the finite element method with its associated numerical techniques for idealization of the structural component, cyclic plasticity models for idealization of the material behavior, and damage accumulation criteria for the fatigue failure.

Diversity and Activity of Communities Inhabiting Plastic Debris in the North Pacific Gyre

PubMed Central

Bryant, Jessica A.; Clemente, Tara M.; Viviani, Donn A.; Fong, Allison A.; Thomas, Kimberley A.; Kemp, Paul; Karl, David M.; White, Angelicque E.

2016-01-01

ABSTRACT Marine plastic debris has become a significant concern in ocean ecosystems worldwide. Little is known, however, about its influence on microbial community structure and function. In 2008, we surveyed microbial communities and metabolic activities in seawater and on plastic on an oceanographic expedition through the “great Pacific garbage patch.” The concentration of plastic particles in surface seawater within different size classes (2 to 5 mm and >5 mm) ranged from 0.35 to 3.7 particles m−3 across sampling stations. These densities and the particle size distribution were consistent with previous values reported in the North Pacific Ocean. Net community oxygen production (NCP = gross primary production − community respiration) on plastic debris was positive and so net autotrophic, whereas NCP in bulk seawater was close to zero. Scanning electron microscopy and metagenomic sequencing of plastic-attached communities revealed the dominance of a few metazoan taxa and a diverse assemblage of photoautotrophic and heterotrophic protists and bacteria. Bryozoa, Cyanobacteria, Alphaproteobacteria, and Bacteroidetes dominated all plastic particles, regardless of particle size. Bacteria inhabiting plastic were taxonomically distinct from the surrounding picoplankton and appeared well adapted to a surface-associated lifestyle. Genes with significantly higher abundances among plastic-attached bacteria included che genes, secretion system genes, and nifH genes, suggesting enrichment for chemotaxis, frequent cell-to-cell interactions, and nitrogen fixation. In aggregate, our findings suggest that plastic debris forms a habitat for complex microbial assemblages that have lifestyles, metabolic pathways, and biogeochemical activities that are distinct from those of free-living planktonic microbial communities. IMPORTANCE Marine plastic debris is a growing concern that has captured the general public’s attention. While the negative impacts of plastic debris on

Diversity and Activity of Communities Inhabiting Plastic Debris in the North Pacific Gyre.

PubMed

Bryant, Jessica A; Clemente, Tara M; Viviani, Donn A; Fong, Allison A; Thomas, Kimberley A; Kemp, Paul; Karl, David M; White, Angelicque E; DeLong, Edward F

2016-01-01

Marine plastic debris has become a significant concern in ocean ecosystems worldwide. Little is known, however, about its influence on microbial community structure and function. In 2008, we surveyed microbial communities and metabolic activities in seawater and on plastic on an oceanographic expedition through the "great Pacific garbage patch." The concentration of plastic particles in surface seawater within different size classes (2 to 5 mm and >5 mm) ranged from 0.35 to 3.7 particles m -3 across sampling stations. These densities and the particle size distribution were consistent with previous values reported in the North Pacific Ocean. Net community oxygen production (NCP = gross primary production - community respiration) on plastic debris was positive and so net autotrophic, whereas NCP in bulk seawater was close to zero. Scanning electron microscopy and metagenomic sequencing of plastic-attached communities revealed the dominance of a few metazoan taxa and a diverse assemblage of photoautotrophic and heterotrophic protists and bacteria. Bryozoa , Cyanobacteria , Alphaproteobacteria , and Bacteroidetes dominated all plastic particles, regardless of particle size. Bacteria inhabiting plastic were taxonomically distinct from the surrounding picoplankton and appeared well adapted to a surface-associated lifestyle. Genes with significantly higher abundances among plastic-attached bacteria included che genes, secretion system genes, and nifH genes, suggesting enrichment for chemotaxis, frequent cell-to-cell interactions, and nitrogen fixation. In aggregate, our findings suggest that plastic debris forms a habitat for complex microbial assemblages that have lifestyles, metabolic pathways, and biogeochemical activities that are distinct from those of free-living planktonic microbial communities. IMPORTANCE Marine plastic debris is a growing concern that has captured the general public's attention. While the negative impacts of plastic debris on oceanic macrobiota

Strings on a Violin: Location Dependence of Frequency Tuning in Active Dendrites.

PubMed

Das, Anindita; Rathour, Rahul K; Narayanan, Rishikesh

2017-01-01

Strings on a violin are tuned to generate distinct sound frequencies in a manner that is firmly dependent on finger location along the fingerboard. Sound frequencies emerging from different violins could be very different based on their architecture, the nature of strings and their tuning. Analogously, active neuronal dendrites, dendrites endowed with active channel conductances, are tuned to distinct input frequencies in a manner that is dependent on the dendritic location of the synaptic inputs. Further, disparate channel expression profiles and differences in morphological characteristics could result in dendrites on different neurons of the same subtype tuned to distinct frequency ranges. Alternately, similar location-dependence along dendritic structures could be achieved through disparate combinations of channel profiles and morphological characteristics, leading to degeneracy in active dendritic spectral tuning. Akin to strings on a violin being tuned to different frequencies than those on a viola or a cello, different neuronal subtypes exhibit distinct channel profiles and disparate morphological characteristics endowing each neuronal subtype with unique location-dependent frequency selectivity. Finally, similar to the tunability of musical instruments to elicit distinct location-dependent sounds, neuronal frequency selectivity and its location-dependence are tunable through activity-dependent plasticity of ion channels and morphology. In this morceau, we explore the origins of neuronal frequency selectivity, and survey the literature on the mechanisms behind the emergence of location-dependence in distinct forms of frequency tuning. As a coda to this composition, we present some future directions for this exciting convergence of biophysical mechanisms that endow a neuron with frequency multiplexing capabilities.

Mecp2 Mediates Experience-Dependent Transcriptional Upregulation of Ryanodine Receptor Type-3

PubMed Central

Torres, Rodrigo F.; Hidalgo, Cecilia; Kerr, Bredford

2017-01-01

Mecp2 is a DNA methylation reader that plays a critical role in experience-dependent plasticity. Increasing evidence supports a role for epigenetic modifications in activity-induced gene expression. Hence, candidate genes related to such phenomena are of great interest. Ryanodine receptors are intracellular calcium channels that contribute to hippocampal synaptic plasticity, dendritic spine remodeling, and participate in learning and memory processes. Here we exposed mice to the enriched environment (EE) paradigm, which through increased stimulation induces experience dependent-plasticity, to explore a role for methyl-cytosines, and Mecp2 in directing Ryanodine receptor 3 (Ryr3) transcriptional activity. EE induced a hippocampal-specific increase in the methylation of discrete cytosines located at a Ryr3 isoform promoter; chromatin immunoprecipitation experiments revealed that EE increased Mecp2 binding to this Ryr3 isoform promoter. Interestingly, the experimental paradigm induced robust Ryr3 upregulation, accompanied by miR132-dependent suppression of p250GAP, a pathway driving synaptogenesis. In contrast to WT mice, Mecp2-null mice showed diminished levels of Ryr3 and displayed impaired EE-induced Ryr3 upregulation, compromising miR132 dependent suppression of p250GAP and experience-dependent structural plasticity. Based on these results, we propose that Mecp2 acts as a transcriptional activator of Ryr3, contributing to experience-dependent plasticity. PMID:28659760

Mecp2 Mediates Experience-Dependent Transcriptional Upregulation of Ryanodine Receptor Type-3.

PubMed

Torres, Rodrigo F; Hidalgo, Cecilia; Kerr, Bredford

2017-01-01

Mecp2 is a DNA methylation reader that plays a critical role in experience-dependent plasticity. Increasing evidence supports a role for epigenetic modifications in activity-induced gene expression. Hence, candidate genes related to such phenomena are of great interest. Ryanodine receptors are intracellular calcium channels that contribute to hippocampal synaptic plasticity, dendritic spine remodeling, and participate in learning and memory processes. Here we exposed mice to the enriched environment (EE) paradigm, which through increased stimulation induces experience dependent-plasticity, to explore a role for methyl-cytosines, and Mecp2 in directing Ryanodine receptor 3 ( Ryr3 ) transcriptional activity. EE induced a hippocampal-specific increase in the methylation of discrete cytosines located at a Ryr3 isoform promoter; chromatin immunoprecipitation experiments revealed that EE increased Mecp2 binding to this Ryr3 isoform promoter. Interestingly, the experimental paradigm induced robust Ryr3 upregulation, accompanied by miR132 -dependent suppression of p250GAP , a pathway driving synaptogenesis. In contrast to WT mice, Mecp2-null mice showed diminished levels of Ryr3 and displayed impaired EE-induced Ryr3 upregulation, compromising miR132 dependent suppression of p250GAP and experience-dependent structural plasticity. Based on these results, we propose that Mecp2 acts as a transcriptional activator of Ryr3 , contributing to experience-dependent plasticity.

The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory

PubMed Central

Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M.; Kerjaschki, Dontscho; Pollak, Daniela D.; Uhrin, Pavel; Monje, Francisco J.

2016-01-01

Abstract Introduction: Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Materials and methods: Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Results: Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. Discussion: This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology.Key messagesPodoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions.Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation.Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these

The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.

PubMed

Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M; Kerjaschki, Dontscho; Pollak, Daniela D; Uhrin, Pavel; Monje, Francisco J

2016-12-01

Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well

Drawing dependent structures, mechanical properties and cyclization behaviors of polyacrylonitrile and polyacrylonitrile/carbon nanotube composite fibers prepared by plasticized spinning.

PubMed

Li, Xiang; Qin, Aiwen; Zhao, Xinzhen; Liu, Dapeng; Wang, Haiye; He, Chunju

2015-09-14

Drawing to change the structural properties and cyclization behaviors of the polyacrylonitrile (PAN) chains in crystalline and amorphous regions is carried out on PAN and PAN/carbon nanotube (CNT) composite fibers. Various characterization methods including Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and thermal gravimetric analysis are used to monitor the structural evolution and cyclization behaviors of the fibers. With an increase of the draw ratio during the plasticized spinning process, the structural parameters of the fibers, i.e. crystallinity and planar zigzag conformation, are decreased at first, and then increased, which are associated with the heat exchange rate and the oriented-crystallization rate. A possible mechanism for plasticized spinning is proposed to explain the changing trends of crystallinity and planar zigzag conformation. PAN and PAN/CNT fibers exhibit various cyclization behaviors induced by drawing, e.g., the initiation temperature for the cyclization (Ti) of PAN fibers is increased with increasing draw ratio, while Ti of PAN/CNT fibers is decreased. Drawing also facilitates cyclization and lowers the percentage of β-amino nitrile for PAN/CNT fibers during the stabilization.

Delay selection by spike-timing-dependent plasticity in recurrent networks of spiking neurons receiving oscillatory inputs.

PubMed

Kerr, Robert R; Burkitt, Anthony N; Thomas, Doreen A; Gilson, Matthieu; Grayden, David B

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem.

Delay Selection by Spike-Timing-Dependent Plasticity in Recurrent Networks of Spiking Neurons Receiving Oscillatory Inputs

PubMed Central

Kerr, Robert R.; Burkitt, Anthony N.; Thomas, Doreen A.; Gilson, Matthieu; Grayden, David B.

2013-01-01

Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem. PMID:23408878

Dynamic Hebbian Cross-Correlation Learning Resolves the Spike Timing Dependent Plasticity Conundrum.

PubMed

Olde Scheper, Tjeerd V; Meredith, Rhiannon M; Mansvelder, Huibert D; van Pelt, Jaap; van Ooyen, Arjen

2017-01-01

Spike Timing-Dependent Plasticity has been found to assume many different forms. The classic STDP curve, with one potentiating and one depressing window, is only one of many possible curves that describe synaptic learning using the STDP mechanism. It has been shown experimentally that STDP curves may contain multiple LTP and LTD windows of variable width, and even inverted windows. The underlying STDP mechanism that is capable of producing such an extensive, and apparently incompatible, range of learning curves is still under investigation. In this paper, it is shown that STDP originates from a combination of two dynamic Hebbian cross-correlations of local activity at the synapse. The correlation of the presynaptic activity with the local postsynaptic activity is a robust and reliable indicator of the discrepancy between the presynaptic neuron and the postsynaptic neuron's activity. The second correlation is between the local postsynaptic activity with dendritic activity which is a good indicator of matching local synaptic and dendritic activity. We show that this simple time-independent learning rule can give rise to many forms of the STDP learning curve. The rule regulates synaptic strength without the need for spike matching or other supervisory learning mechanisms. Local differences in dendritic activity at the synapse greatly affect the cross-correlation difference which determines the relative contributions of different neural activity sources. Dendritic activity due to nearby synapses, action potentials, both forward and back-propagating, as well as inhibitory synapses will dynamically modify the local activity at the synapse, and the resulting STDP learning rule. The dynamic Hebbian learning rule ensures furthermore, that the resulting synaptic strength is dynamically stable, and that interactions between synapses do not result in local instabilities. The rule clearly demonstrates that synapses function as independent localized computational entities, each

Visual Cortex Plasticity: A Complex Interplay of Genetic and Environmental Influences

PubMed Central

Maya-Vetencourt, José Fernando; Origlia, Nicola

2012-01-01

The central nervous system architecture is highly dynamic and continuously modified by sensory experience through processes of neuronal plasticity. Plasticity is achieved by a complex interplay of environmental influences and physiological mechanisms that ultimately activate intracellular signal transduction pathways regulating gene expression. In addition to the remarkable variety of transcription factors and their combinatorial interaction at specific gene promoters, epigenetic mechanisms that regulate transcription have emerged as conserved processes by which the nervous system accomplishes the induction of plasticity. Experience-dependent changes of DNA methylation patterns and histone posttranslational modifications are, in fact, recruited as targets of plasticity-associated signal transduction mechanisms. Here, we shall concentrate on structural and functional consequences of early sensory deprivation in the visual system and discuss how intracellular signal transduction pathways associated with experience regulate changes of chromatin structure and gene expression patterns that underlie these plastic phenomena. Recent experimental evidence for mechanisms of cross-modal plasticity following congenital or acquired sensory deprivation both in human and animal models will be considered as well. We shall also review different experimental strategies that can be used to achieve the recovery of sensory functions after long-term deprivation in humans. PMID:22852098

Network Supervision of Adult Experience and Learning Dependent Sensory Cortical Plasticity.

PubMed

Blake, David T

2017-06-18

The brain is capable of remodeling throughout life. The sensory cortices provide a useful preparation for studying neuroplasticity both during development and thereafter. In adulthood, sensory cortices change in the cortical area activated by behaviorally relevant stimuli, by the strength of response within that activated area, and by the temporal profiles of those responses. Evidence supports forms of unsupervised, reinforcement, and fully supervised network learning rules. Studies on experience-dependent plasticity have mostly not controlled for learning, and they find support for unsupervised learning mechanisms. Changes occur with greatest ease in neurons containing α-CamKII, which are pyramidal neurons in layers II/III and layers V/VI. These changes use synaptic mechanisms including long term depression. Synaptic strengthening at NMDA-containing synapses does occur, but its weak association with activity suggests other factors also initiate changes. Studies that control learning find support of reinforcement learning rules and limited evidence of other forms of supervised learning. Behaviorally associating a stimulus with reinforcement leads to a strengthening of cortical response strength and enlarging of response area with poor selectivity. Associating a stimulus with omission of reinforcement leads to a selective weakening of responses. In some preparations in which these associations are not as clearly made, neurons with the most informative discharges are relatively stronger after training. Studies analyzing the temporal profile of responses associated with omission of reward, or of plasticity in studies with different discriminanda but statistically matched stimuli, support the existence of limited supervised network learning. © 2017 American Physiological Society. Compr Physiol 7:977-1008, 2017. Copyright © 2017 John Wiley & Sons, Inc.

From Lobster Shells to Plastic Objects: A Bioplastics Activity

ERIC Educational Resources Information Center

Hudson, Reuben; Glaisher, Samuel; Bishop, Alexandra; Katz, Jeffrey L.

2015-01-01

A multiple day activity for students to create large-scale plastic objects from the biopolymer chitin (major component of lobster, crab, and shrimp shells) is described. The plastic objects created are durable and made from benign materials, making them suitable for students to take home to play with. Since the student-created plastic objects are…

Elasto-limited plastic analysis of structures for probabilistic conditions

NASA Astrophysics Data System (ADS)

Movahedi Rad, M.

2018-06-01

With applying plastic analysis and design methods, significant saving in material can be obtained. However, as a result of this benefit excessive plastic deformations and large residual displacements might develop, which in turn might lead to unserviceability and collapse of the structure. In this study, for deterministic problem the residual deformation of structures is limited by considering a constraint on the complementary strain energy of the residual forces. For probabilistic problem the constraint for the complementary strain energy of the residual forces is given randomly and critical stresses updated during the iteration. Limit curves are presented for the plastic limit load factors. The results show that these constraints have significant effects on the load factors. The formulations of the deterministic and probabilistic problems lead to mathematical programming which are solved by the use of nonlinear algorithm.

Spontaneous Activity Drives Local Synaptic Plasticity In Vivo.

PubMed

Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, Christian

2015-07-15

Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (<12 μm) become depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an "out-of-sync, lose-your-link" fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuronal plasticity and antidepressant actions

PubMed Central

Castrén, Eero; Hen, René

2013-01-01

Antidepressant treatments enhance plasticity and increase neurogenesis in the adult brain, but it has been unclear how these effects influence mood. We propose that like environmental enrichment and exercise, antidepressant treatments enhance adaptability by increasing structural variability within the nervous system at many levels, from proliferating precursors to immature synaptic contacts. Conversely, sensory deprivation and chronic stress reduce this structural variability. Activity-dependent competition within the mood-related circuits, guided by rehabilitation, then selects for the survival and stabilization of those structures that best represent the internal or external milieu. Increased variability together with competition-mediated selection facilitates normal function, such as pattern separation within the dentate gyrus and other mood-related circuits, thereby enhancing adaptability towards novel experiences. PMID:23380665

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

PubMed Central

Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

2017-01-01

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a “maladaptive” strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke. PMID:28706475

Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System.

PubMed

Gennaro, Mariangela; Mattiello, Alessandro; Mazziotti, Raffaele; Antonelli, Camilla; Gherardini, Lisa; Guzzetta, Andrea; Berardi, Nicoletta; Cioni, Giovanni; Pizzorusso, Tommaso

2017-01-01

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

Avalanches and plasticity for colloids in a time dependent optical trap

DOE PAGES

Olson Reichhardt, Cynthia Jane; McDermott, Danielle Marie; Reichhardt, Charles

2015-08-25

Here, with the use of optical traps it is possible to confine assemblies of colloidal particles in two-dimensional and quasi-one-dimensional arrays. Here we examine how colloidal particles rearrange in a quasi-one-dimensional trap with a time dependent confining potential. The particle motion occurs both through slow elastic uniaxial distortions as well as through abrupt large-scale two-dimensional avalanches associated with plastic rearrangements. During the avalanches the particle velocity distributions extend over a broad range and can be fit to a power law consistent with other studies of plastic events mediated by dislocations.

Experience-dependent plasticity from eye opening enables lasting, visual cortex-dependent enhancement of motion vision.

PubMed

Prusky, Glen T; Silver, Byron D; Tschetter, Wayne W; Alam, Nazia M; Douglas, Robert M

2008-09-24

Developmentally regulated plasticity of vision has generally been associated with "sensitive" or "critical" periods in juvenile life, wherein visual deprivation leads to loss of visual function. Here we report an enabling form of visual plasticity that commences in infant rats from eye opening, in which daily threshold testing of optokinetic tracking, amid otherwise normal visual experience, stimulates enduring, visual cortex-dependent enhancement (>60%) of the spatial frequency threshold for tracking. The perceptual ability to use spatial frequency in discriminating between moving visual stimuli is also improved by the testing experience. The capacity for inducing enhancement is transitory and effectively limited to infancy; however, enhanced responses are not consolidated and maintained unless in-kind testing experience continues uninterrupted into juvenile life. The data show that selective visual experience from infancy can alone enable visual function. They also indicate that plasticity associated with visual deprivation may not be the only cause of developmental visual dysfunction, because we found that experientially inducing enhancement in late infancy, without subsequent reinforcement of the experience in early juvenile life, can lead to enduring loss of function.

Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D β-Lactamase of Acinetobacter baumannii.

PubMed

Pratap, Shivendra; Katiki, Madhusudhanarao; Gill, Preet; Kumar, Pravindra; Golemi-Kotra, Dasantila

2016-01-01

Carbapenem-hydrolyzing class D β-lactamases (CHDLs) are a subgroup of class D β-lactamases, which are enzymes that hydrolyze β-lactams. They have attracted interest due to the emergence of multidrug-resistant Acinetobacter baumannii, which is not responsive to treatment with carbapenems, the usual antibiotics of choice for this bacterium. Unlike other class D β-lactamases, these enzymes efficiently hydrolyze carbapenem antibiotics. To explore the structural requirements for the catalysis of carbapenems by these enzymes, we determined the crystal structure of the OXA-58 CHDL of A. baumannii following acylation of its active-site serine by a 6α-hydroxymethyl penicillin derivative that is a structural mimetic for a carbapenem. In addition, several point mutation variants of the active site of OXA-58, as identified by the crystal structure analysis, were characterized kinetically. These combined studies confirm the mechanistic relevance of a hydrophobic bridge formed over the active site. This structural feature is suggested to stabilize the hydrolysis-productive acyl-enzyme species formed from the carbapenem substrates of this enzyme. Furthermore, our structural studies provide strong evidence that the hydroxyethyl group of carbapenems samples different orientations in the active sites of CHDLs, and the optimum orientation for catalysis depends on the topology of the active site allowing proper closure of the active site. We propose that CHDLs use the plasticity of the active site to drive the mechanism of carbapenem hydrolysis toward efficiency. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Arc restores juvenile plasticity in adult mouse visual cortex

PubMed Central

Jenks, Kyle R.; Kim, Taekeun; Pastuzyn, Elissa D.; Okuno, Hiroyuki; Taibi, Andrew V.; Bear, Mark F.

2017-01-01

The molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here, we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild-type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation. PMID:28790183

Structural and Functional Plasticity in the Maternal Brain Circuitry

ERIC Educational Resources Information Center

Pereira, Mariana

2016-01-01

Parenting recruits a distributed network of brain structures (and neuromodulators) that coordinates caregiving responses attuned to the young's affect, needs, and developmental stage. Many of these structures and connections undergo significant structural and functional plasticity, mediated by the interplay between maternal hormones and social…

Psychedelics Promote Structural and Functional Neural Plasticity.

PubMed

Ly, Calvin; Greb, Alexandra C; Cameron, Lindsay P; Wong, Jonathan M; Barragan, Eden V; Wilson, Paige C; Burbach, Kyle F; Soltanzadeh Zarandi, Sina; Sood, Alexander; Paddy, Michael R; Duim, Whitney C; Dennis, Megan Y; McAllister, A Kimberley; Ori-McKenney, Kassandra M; Gray, John A; Olson, David E

2018-06-12

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Experience-Dependent Plasticity in Accessory Olfactory Bulb Interneurons following Male-Male Social Interaction.

PubMed

Cansler, Hillary L; Maksimova, Marina A; Meeks, Julian P

2017-07-26

Chemosensory information processing in the mouse accessory olfactory system guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC-interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe targeted electrophysiological studies of AOB inhibitory internal granule cells (IGCs), many of which upregulate the immediate-early gene Arc after male-male social experience. Following the resident-intruder paradigm, Arc -expressing IGCs in acute AOB slices from resident males displayed stronger excitation than nonexpressing neighbors when sensory inputs were stimulated. The increased excitability of Arc -expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated I H currents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident-intruder encounters. These results reveal that nonmating behaviors drive AOB inhibitory plasticity and indicate that increased MC inhibition involves intrinsic excitability changes in Arc -expressing interneurons. SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is a site of experience-dependent plasticity between excitatory mitral cells (MCs) and inhibitory internal granule cells (IGCs), but the physiological mechanisms and behavioral conditions driving this plasticity remain unclear. Here, we report studies of AOB neuronal plasticity following male-male social chemosensory encounters. We show that the plasticity

Experience-Dependent Plasticity in Accessory Olfactory Bulb Interneurons following Male–Male Social Interaction

PubMed Central

Maksimova, Marina A.

2017-01-01

Chemosensory information processing in the mouse accessory olfactory system guides the expression of social behavior. After salient chemosensory encounters, the accessory olfactory bulb (AOB) experiences changes in the balance of excitation and inhibition at reciprocal synapses between mitral cells (MCs) and local interneurons. The mechanisms underlying these changes remain controversial. Moreover, it remains unclear whether MC–interneuron plasticity is unique to specific behaviors, such as mating, or whether it is a more general feature of the AOB circuit. Here, we describe targeted electrophysiological studies of AOB inhibitory internal granule cells (IGCs), many of which upregulate the immediate-early gene Arc after male–male social experience. Following the resident–intruder paradigm, Arc-expressing IGCs in acute AOB slices from resident males displayed stronger excitation than nonexpressing neighbors when sensory inputs were stimulated. The increased excitability of Arc-expressing IGCs was not correlated with changes in the strength or number of excitatory synapses with MCs but was instead associated with increased intrinsic excitability and decreased HCN channel-mediated IH currents. Consistent with increased inhibition by IGCs, MCs responded to sensory input stimulation with decreased depolarization and spiking following resident–intruder encounters. These results reveal that nonmating behaviors drive AOB inhibitory plasticity and indicate that increased MC inhibition involves intrinsic excitability changes in Arc-expressing interneurons. SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is a site of experience-dependent plasticity between excitatory mitral cells (MCs) and inhibitory internal granule cells (IGCs), but the physiological mechanisms and behavioral conditions driving this plasticity remain unclear. Here, we report studies of AOB neuronal plasticity following male–male social chemosensory encounters. We show that the plasticity

Context-Dependent Plastic Response during Egg-Laying in a Widespread Newt Species

PubMed Central

Tóth, Zoltán

2015-01-01

Previous research on predator-induced phenotypic plasticity mostly focused on responses in morphology, developmental time and/or behaviour during early life stages, but the potential significance of anticipatory parental responses has been investigated less often. In this study I examined behavioural and maternal responses of gravid female smooth newts, Lissotriton vulgaris, in the presence of chemical cues originating from invertebrate predators, Acilius sulcatus water beetles and Aeshna cyanea dragonfly larvae. More specifically, I tested the extent of oviposition preference, plasticity in egg-wrapping behaviour and plasticity in egg size when females had the possibility to lay eggs at oviposition sites with and without predator cues during overnight trials. I found that individuals did not avoid laying eggs in the environment with predator cues; however, individuals that deposited eggs into both environments adjusted the size of the laid eggs to the perceived environment. Females deposited larger eggs earlier in the season but egg size decreased with time in the absence of predator cues, whereas individuals laid eggs of average size throughout the investigated reproductive period when such cues were present. Also, egg size was found to be positively related to hatching success. Individuals did not adjust their wrapping behaviour to the presence of predator cues, but females differed in the extent of egg-wrapping between ponds. Females’ body mass and tail depth were also different between ponds, whereas their body size was positively associated with egg size. According to these results, female smooth newts have the potential to exhibit activational plasticity and invest differently into eggs depending on temporal and environmental factors. Such an anticipatory response may contribute to the success of this caudate species under a wide range of predator regimes at its natural breeding habitats. PMID:26291328

Light reintroduction after dark exposure reactivates plasticity in adults via perisynaptic activation of MMP-9

PubMed Central

2017-01-01

The sensitivity of ocular dominance to regulation by monocular deprivation is the canonical model of plasticity confined to a critical period. However, we have previously shown that visual deprivation through dark exposure (DE) reactivates critical period plasticity in adults. Previous work assumed that the elimination of visual input was sufficient to enhance plasticity in the adult mouse visual cortex. In contrast, here we show that light reintroduction (LRx) after DE is responsible for the reactivation of plasticity. LRx triggers degradation of the ECM, which is blocked by pharmacological inhibition or genetic ablation of matrix metalloproteinase-9 (MMP-9). LRx induces an increase in MMP-9 activity that is perisynaptic and enriched at thalamo-cortical synapses. The reactivation of plasticity by LRx is absent in Mmp9−/− mice, and is rescued by hyaluronidase, an enzyme that degrades core ECM components. Thus, the LRx-induced increase in MMP-9 removes constraints on structural and functional plasticity in the mature cortex. PMID:28875930

Computational implications of activity-dependent neuronal processes

NASA Astrophysics Data System (ADS)

Goldman, Mark Steven

Synapses, the connections between neurons, often fail to transmit a large percentage of the action potentials that they receive. I describe several models of synaptic transmission at a single stochastic synapse with an activity-dependent probability of transmission and demonstrate how synaptic transmission failures may increase the efficiency with which a synapse transmits information. Spike trains in the visual cortex of freely viewing monkeys have positive auto correlations that are indicative of a redundant representation of the information they contain. I show how a synapse with activity-dependent transmission failures modeled after those occurring in visual cortical synapses can remove this redundancy by transmitting a decorrelated subset of the spike trains it receives. I suggest that redundancy reduction at individual synapses saves synaptic resources while increasing the sensitivity of the postsynaptic neuron to information arriving along many inputs. For a neuron receiving input from many decorrelating synapses, my analysis leads to a prediction of the number of visual inputs to a neuron and the cross-correlations between these inputs and suggests that the time scale of synaptic dynamics observed in sensory areas corresponds to a fundamental time scale for processing sensory information. Systems with activity-dependent changes in their parameters, or plasticity, often display a wide variability in their individual components that belies the stability of their function, Motivated by experiments demonstrating that identified neurons with stereotyped function can have a large variability in the densities of their ion channels, or ionic conductances, I build a conductance-based model of a single neuron. The neuron's firing activity is relatively insensitive to changes in certain combinations of conductances, but markedly sensitive to changes in other combinations. Using a combined modeling and experimental approach, I show that neuromodulators and regulatory

Impaired activity-dependent FMRP translation and enhanced mGluR-dependent LTD in Fragile X premutation mice

PubMed Central

Iliff, Adam J.; Renoux, Abigail J.; Krans, Amy; Usdin, Karen; Sutton, Michael A.; Todd, Peter K.

2013-01-01

Fragile X premutation-associated disorders, including Fragile X-associated Tremor Ataxia Syndrome, result from unmethylated CGG repeat expansions in the 5′ untranslated region (UTR) of the FMR1 gene. Premutation-sized repeats increase FMR1 transcription but impair rapid translation of the Fragile X mental retardation protein (FMRP), which is absent in Fragile X Syndrome (FXS). Normally, FMRP binds to RNA and regulates metabotropic glutamate receptor (mGluR)-mediated synaptic translation, allowing for dendritic synthesis of several proteins. FMRP itself is also synthesized at synapses in response to mGluR activation. However, the role of activity-dependent translation of FMRP in synaptic plasticity and Fragile X-premutation-associated disorders is unknown. To investigate this question, we utilized a CGG knock-in mouse model of the Fragile X premutation with 120–150 CGG repeats in the mouse Fmr1 5′ UTR. These mice exhibit increased Fmr1 mRNA production but impaired FMRP translational efficiency, leading to a modest reduction in basal FMRP expression. Cultured hippocampal neurons and synaptoneurosomes derived from CGG KI mice demonstrate impaired FMRP translation in response to the group I mGluR agonist 3,5-dihydroxyphenylglycine. Electrophysiological analysis reveals enhanced mGluR-mediated long-term depression (mGluR-LTD) at CA3–CA1 synapses in acute hippocampal slices prepared from CGG KI mice relative to wild-type littermates, similar to Fmr1 knockout mice. However, unlike mGluR-LTD in mice completely lacking FMRP, mGluR-LTD in CGG knock-in mice remains dependent on new protein synthesis. These studies demonstrate partially overlapping synaptic plasticity phenotypes in mouse models of FXS and Fragile X premutation disorders and support a role for activity-dependent synthesis of FMRP in enduring forms of synaptic plasticity. PMID:23250915

[Physical activity: positive impact on brain plasticity].

PubMed

Achiron, Anat; Kalron, Alon

2008-03-01

The central nervous system has a unique capability of plasticity that enables a single neuron or a group of neurons to undergo functional and constructional changes that are important to learning processes and for compensation of brain damage. The current review aims to summarize recent data related to the effects of physical activity on brain plasticity. In the last decade it was reported that physical activity can affect and manipulate neuronal connections, synaptic activity and adaptation to new neuronal environment following brain injury. One of the most significant neurotrophic factors that is critical for synaptic re-organization and is influenced by physical activity is brain-derived neurotrophic factor (BDNF). The frequency of physical activity and the intensity of exercises are of importance to brain remodeling, support neuronal survival and positively affect rehabilitation therapy. Physical activity should be employed as a tool to improve neural function in healthy subjects and in patients suffering from neurological damage.

Structure-dependent binding and activation of perfluorinated compounds on human peroxisome proliferator-activated receptor γ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Lianying; College of Life Science, Dezhou University, Dezhou 253023; Ren, Xiao-Min

2014-09-15

Perfluorinated compounds (PFCs) have been shown to disrupt lipid metabolism and even induce cancer in rodents through activation of peroxisome proliferator-activated receptors (PPARs). Lines of evidence showed that PPARα was activated by PFCs. However, the information on the binding interactions between PPARγ and PFCs and subsequent alteration of PPARγ activity is still limited and sometimes inconsistent. In the present study, in vitro binding of 16 PFCs to human PPARγ ligand binding domain (hPPARγ-LBD) and their activity on the receptor in cells were investigated. The results showed that the binding affinity was strongly dependent on their carbon number and functional group.more » For the eleven perfluorinated carboxylic acids (PFCAs), the binding affinity increased with their carbon number from 4 to 11, and then decreased slightly. The binding affinity of the three perfluorinated sulfonic acids (PFSAs) was stronger than their PFCA counterparts. No binding was detected for the two fluorotelomer alcohols (FTOHs). Circular dichroim spectroscopy showed that PFC binding induced distinctive structural change of the receptor. In dual luciferase reporter assays using transiently transfected Hep G2 cells, PFCs acted as hPPARγ agonists, and their potency correlated with their binding affinity with hPPARγ-LBD. Molecular docking showed that PFCs with different chain length bind with the receptor in different geometry, which may contribute to their differences in binding affinity and transcriptional activity. - Highlights: • Binding affinity between PFCs and PPARγ was evaluated for the first time. • The binding strength was dependent on fluorinated carbon chain and functional group. • PFC binding induced distinctive structural change of the receptor. • PFCs could act as hPPARγ agonists in Hep G2 cells.« less

Probing elastically or plastically induced structural heterogeneities in bulk metallic glasses by nanoindentation pop-in tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Tingkun; Gao, Yanfei; Bei, Hongbin

Shear banding dynamics in bulk metallic glasses (BMGs) is manifested by the spatiotemporal evolution of strain fields which in turn depend on structural heterogeneities. The spacing of these heterogeneities, as a characteristic length scale, was determined from the analysis of nanoindentation pop-in tests using a stochastic model. Furthermore, the pre-stress by elastic bending and residual stress by plastic bending of BMG plates were found to dramatically decrease such spacings, thus increasing heterogeneity density and mechanically rejuvenating the glass structure.

Probing elastically or plastically induced structural heterogeneities in bulk metallic glasses by nanoindentation pop-in tests

DOE PAGES

Liu, Tingkun; Gao, Yanfei; Bei, Hongbin

2017-07-21

Shear banding dynamics in bulk metallic glasses (BMGs) is manifested by the spatiotemporal evolution of strain fields which in turn depend on structural heterogeneities. The spacing of these heterogeneities, as a characteristic length scale, was determined from the analysis of nanoindentation pop-in tests using a stochastic model. Furthermore, the pre-stress by elastic bending and residual stress by plastic bending of BMG plates were found to dramatically decrease such spacings, thus increasing heterogeneity density and mechanically rejuvenating the glass structure.

Computational modeling of neural plasticity for self-organization of neural networks.

PubMed

Chrol-Cannon, Joseph; Jin, Yaochu

2014-11-01

Self-organization in biological nervous systems during the lifetime is known to largely occur through a process of plasticity that is dependent upon the spike-timing activity in connected neurons. In the field of computational neuroscience, much effort has been dedicated to building up computational models of neural plasticity to replicate experimental data. Most recently, increasing attention has been paid to understanding the role of neural plasticity in functional and structural neural self-organization, as well as its influence on the learning performance of neural networks for accomplishing machine learning tasks such as classification and regression. Although many ideas and hypothesis have been suggested, the relationship between the structure, dynamics and learning performance of neural networks remains elusive. The purpose of this article is to review the most important computational models for neural plasticity and discuss various ideas about neural plasticity's role. Finally, we suggest a few promising research directions, in particular those along the line that combines findings in computational neuroscience and systems biology, and their synergetic roles in understanding learning, memory and cognition, thereby bridging the gap between computational neuroscience, systems biology and computational intelligence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Learning-Dependent Plasticity of the Barrel Cortex Is Impaired by Restricting GABA-Ergic Transmission.

PubMed

Posluszny, Anna; Liguz-Lecznar, Monika; Turzynska, Danuta; Zakrzewska, Renata; Bielecki, Maksymilian; Kossut, Malgorzata

2015-01-01

Experience-induced plastic changes in the cerebral cortex are accompanied by alterations in excitatory and inhibitory transmission. Increased excitatory drive, necessary for plasticity, precedes the occurrence of plastic change, while decreased inhibitory signaling often facilitates plasticity. However, an increase of inhibitory interactions was noted in some instances of experience-dependent changes. We previously reported an increase in the number of inhibitory markers in the barrel cortex of mice after fear conditioning engaging vibrissae, observed concurrently with enlargement of the cortical representational area of the row of vibrissae receiving conditioned stimulus (CS). We also observed that an increase of GABA level accompanied the conditioning. Here, to find whether unaltered GABAergic signaling is necessary for learning-dependent rewiring in the murine barrel cortex, we locally decreased GABA production in the barrel cortex or reduced transmission through GABAA receptors (GABAARs) at the time of the conditioning. Injections of 3-mercaptopropionic acid (3-MPA), an inhibitor of glutamic acid decarboxylase (GAD), into the barrel cortex prevented learning-induced enlargement of the conditioned vibrissae representation. A similar effect was observed after injection of gabazine, an antagonist of GABAARs. At the behavioral level, consistent conditioned response (cessation of head movements in response to CS) was impaired. These results show that appropriate functioning of the GABAergic system is required for both manifestation of functional cortical representation plasticity and for the development of a conditioned response.

Novel Experience Induces Persistent Sleep-Dependent Plasticity in the Cortex but not in the Hippocampus

PubMed Central

Ribeiro, Sidarta; Shi, Xinwu; Engelhard, Matthew; Zhou, Yi; Zhang, Hao; Gervasoni, Damien; Lin, Shi-Chieh; Wada, Kazuhiro; Lemos, Nelson A.M.

2007-01-01

Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS) and rapid eye movement (REM) sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP), and expression levels of plasticity-related immediate-early genes (IEG) arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours) than in the hippocampus (minutes). During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10–14 Hz) but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time. PMID:18982118

Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

PubMed

Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

2015-11-01

The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

Endocrine mediated phenotypic plasticity: condition-dependent effects of juvenile hormone on dominance and fertility of wasp queens.

PubMed

Tibbetts, Elizabeth A; Izzo, Amanda S

2009-11-01

There has been increasing interest in the mechanisms that mediate behavioral and physiological plasticity across individuals with similar genotypes. Some of the most dramatic plasticity is found within and between social insect castes. For example, Polistes wasp queens can nest alone, dominate a group of cooperative queens, or act as worker-like subordinates who rarely reproduce. Previous work suggests that condition-dependent endocrine responses may play a role in plasticity between castes in the hymenoptera. Here, we test whether condition-dependent endocrine responses influence plasticity within castes in the wasp Polistes dominulus. We experimentally manipulate juvenile hormone (JH) titers in nest-founding queens and assess whether JH mediates variation in behavior and physiology. JH generally increased dominance and fertility of queens, but JH's effects were not uniform across individuals. JH had a stronger effect on the dominance and fertility of large individuals and individuals with facial patterns advertising high quality than on the dominance and fertility of small individuals and those advertising low quality. These results demonstrate that JH has condition-dependent effects. As such, they clarify how JH can mediate different behaviors in well nourished queens and poorly nourished workers. Many Polistes queens nest cooperatively with other queens, so condition-dependent hormonal responses provide a mechanism for queens to adaptively allocate energy based on their probability of successfully becoming the dominant queen. Research on the endocrine basis of plasticity often focuses on variation in endocrine titers alone. However, differential endocrine responses are likely to be a widespread mechanism mediating behavioral and physiological plasticity.

Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity

PubMed Central

Smith, Milo R.; Burman, Poromendro

2016-01-01

Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders. PMID:28101530

Bidirectional synaptic structural plasticity after chronic cocaine administration occurs through Rap1 small GTPase signaling

PubMed Central

Cahill, Michael E.; Bagot, Rosemary C.; Gancarz, Amy M.; Walker, Deena M.; Sun, HaoSheng; Wang, Zi-Jun; Heller, Elizabeth A.; Feng, Jian; Kennedy, Pamela J.; Koo, Ja Wook; Cates, Hannah M.; Neve, Rachael L.; Shen, Li; Dietz, David M.

2016-01-01

Summary Dendritic spines are the sites of most excitatory synapses in the CNS, and opposing alterations in the synaptic structure of medium spiny neurons (MSNs) of the nucleus accumbens, a primary brain reward region, are seen at early vs. late time points after cocaine administration. Here we investigate the time-dependent molecular and biochemical processes that regulate this bidirectional synaptic structural plasticity of NAc MSNs and associated changes in cocaine reward in response to chronic cocaine exposure. Our findings reveal key roles for the bidirectional synaptic expression of the Rap1b small GTPase and an associated local-synaptic protein translation network in this process. The transcriptional mechanisms and pathway-specific inputs to NAc that regulate Rap1b expression are also characterized. Collectively, these findings provide a precise mechanism by which nuclear to synaptic interactions induce “metaplasticity” in NAc MSNs, and we reveal the specific effects of this plasticity on reward behavior in a brain circuit-specific manner. PMID:26844834

CX3CR1 Deficiency Alters Hippocampal-Dependent Plasticity Phenomena Blunting the Effects of Enriched Environment

PubMed Central

Maggi, Laura; Scianni, Maria; Branchi, Igor; D’Andrea, Ivana; Lauro, Clotilde; Limatola, Cristina

2011-01-01

In recent years several evidence demonstrated that some features of hippocampal biology, like neurogenesis, synaptic transmission, learning, and memory performances are deeply modulated by social, motor, and sensorial experiences. Fractalkine/CX3CL1 is a transmembrane chemokine abundantly expressed in the brain by neurons, where it modulates glutamatergic transmission and long-term plasticity processes regulating the intercellular communication between glia and neurons, being its specific receptor CX3CR1 expressed by microglia. In this paper we investigated the role of CX3CL1/CX3CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX3CR1GFP/GFP mice were exposed to long-lasting-enriched environment (EE) and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG). We found that CX3CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE. In contrast, exposure to EE increased the number and migration of neural progenitors in the DG of both wt and CX3CR1GFP/GFP mice. These data indicate that CX3CL1/CX3CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions. PMID:22025910

Myelination: an overlooked mechanism of synaptic plasticity?

PubMed

Fields, R Douglas

2005-12-01

Myelination of the brain continues through childhood into adolescence and early adulthood--the question is, Why? Two new articles provide intriguing evidence that myelination may be an underappreciated mechanism of activity-dependent nervous system plasticity: one study reported increased myelination associated with extensive piano playing, another indicated that rats have increased myelination of the corpus callosum when raised in environments providing increased social interaction and cognitive stimulation. These articles make it clear that activity-dependent effects on myelination cannot be considered strictly a developmental event. They raise the question of whether myelination is an overlooked mechanism of activity-dependent plasticity, extending in humans until at least age 30. It has been argued that regulating the speed of conduction across long fiber tracts would have a major influence on synaptic response, by coordinating the timing of afferent input to maximize temporal summation. The increase in synaptic amplitude could be as large as neurotransmitter-based mechanisms of plasticity, such as LTP. These new findings raise a larger question: How did the oligodendrocytes know they were practicing the piano or that their environment was socially complex?

Neuromodulation, development and synaptic plasticity.

PubMed

Foehring, R C; Lorenzon, N M

1999-03-01

We discuss parallels in the mechanisms underlying use-dependent synaptic plasticity during development and long-term potentiation (LTP) and long-term depression (LTD) in neocortical synapses. Neuromodulators, such as norepinephrine, serotonin, and acetylcholine have also been implicated in regulating both developmental plasticity and LTP/LTD. There are many potential levels of interaction between neuromodulators and plasticity. Ion channels are substrates for modulation in many cell types. We discuss examples of modulation of voltage-gated Ca2+ channels and Ca(2+)-dependent K+ channels and the consequences for neocortical pyramidal cell firing behaviour. At the time when developmental plasticity is most evident in rat cortex, the substrate for modulation is changing as the densities and relative proportions of various ion channels types are altered during ontogeny. We discuss examples of changes in K+ and Ca2+ channels and the consequence for modulation of neuronal activity.

Histone methyltransferase Ash1L mediates activity-dependent repression of neurexin-1α

PubMed Central

Zhu, Τao; Liang, Chen; Li, Dongdong; Tian, Miaomiao; Liu, Sanxiong; Gao, Guanjun; Guan, Ji-Song

2016-01-01

Activity-dependent transcription is critical for the regulation of long-term synaptic plasticity and plastic rewiring in the brain. Here, we report that the transcription of neurexin1α (nrxn1α), a presynaptic adhesion molecule for synaptic formation, is regulated by transient neuronal activation. We showed that 10 minutes of firing at 50 Hz in neurons repressed the expression of nrxn1α for 24 hours in a primary cortical neuron culture through a transcriptional repression mechanism. By performing a screening assay using a synthetic zinc finger protein (ZFP) to pull down the proteins enriched near the nrxn1α promoter region in vivo, we identified that Ash1L, a histone methyltransferase, is enriched in the nrxn1α promoter. Neuronal activity triggered binding of Ash1L to the promoter and enriched the histone marker H3K36me2 at the nrxn1α promoter region. Knockout of Ash1L in mice completely abolished the activity-dependent repression of nrxn1α. Taken together, our results reveal that a novel process of activity-dependent transcriptional repression exists in neurons and that Ash1L mediates the long-term repression of nrxn1α, thus implicating an important role for epigenetic modification in brain functioning. PMID:27229316

Sustained neuronal activity generated by glial plasticity

PubMed Central

Pirttimaki, Tiina M.; Hall, Stephen D.; Parri, H. Rheinallt

2011-01-01

Astrocytes release gliotransmitters, notably glutamate, that can affect neuronal and synaptic activity. In particular, astrocytic glutamate release results in the generation of N-methyl D-aspartate receptor (NMDA-R) mediated slow inward currents (SICs) in neurons. However, factors underlying the emergence of SICs, and their physiological roles are largely unknown. Here we show that, in acute slices of rat somatosensory thalamus, stimulation of Lemniscal or cortical afferents results in a sustained increase of SICs in thalamocortical (TC) neurons that outlasts the duration of the stimulus by an hour. This long term enhancement (LTE) of astrocytic glutamate release is induced by group I metabotropic glutamate receptors (mGluRs), and is dependent on astrocytic intracellular calcium ([Ca2+]i). Neuronal SICs are mediated by extrasynaptic NR2B subunit-containing NMDA-Rs and are capable of eliciting bursts. These are distinct from T-type Ca2+ channel dependent bursts of action potentials, and are synchronized in neighboring TC neurons. These findings describe a previously unrecognized form of excitatory, non-synaptic plasticity in the central nervous system (CNS) that feeds forward to generate local neuronal firing long after stimulus termination. PMID:21613477

The strain path dependence of plastic deformation response of AA5754: Experiment and modeling

NASA Astrophysics Data System (ADS)

Pham, Minh-Son; Hu, Lin; Iadicola, Mark; Creuziger, Adam; Rollett, Anthony D.

2013-12-01

This work presents modeling of experiments on a balanced biaxial (BB) pre-strained AA5754 alloy, subsequently reloaded uniaxially along the rolling direction and transverse direction. The material exhibits a complex plastic deformation response during the change in strain path due to 1) crystallographic texture, 2) aging (interactions between dislocations and Mg atoms) and 3) recovery (annihilation and re-arrangement of dislocations). With a BB prestrain of about 5 %, the aging process is dominant, and the yield strength for uniaxially deformed samples is observed to be higher than the flow stress during BB straining. The strain hardening rate after changing path is, however, lower than that for pre-straining. Higher degrees of pre-straining make the dynamic recovery more active. The dynamic recovery at higher strain levels compensates for the aging effect, and results in: 1) a reduction of the yield strength, and 2) an increase in the hardening rate of re-strained specimens along other directions. The yield strength of deformed samples is further reduced if these samples are left at room temperature to let static recovery occur. The synergistic influences of texture condition, aging and recovery processes on the material response make the modeling of strain path dependence of mechanical behavior of AA5754 challenging. In this study, the influence of crystallographic texture is taken into account by incorporating the latent hardening into a visco-plastic self-consistent model. Different strengths of dislocation glide interaction models in 24 slip systems are used to represent the latent hardening. Moreover, the aging and recovery effects are also included into the latent hardening model by considering strong interactions between dislocations and dissolved atom Mg and the microstructural evolution. These microstructural considerations provide a powerful capability to successfully describe the strain path dependence of plastic deformation behavior of AA5754.

Bayesian Computation Emerges in Generic Cortical Microcircuits through Spike-Timing-Dependent Plasticity

PubMed Central

Nessler, Bernhard; Pfeiffer, Michael; Buesing, Lars; Maass, Wolfgang

2013-01-01

The principles by which networks of neurons compute, and how spike-timing dependent plasticity (STDP) of synaptic weights generates and maintains their computational function, are unknown. Preceding work has shown that soft winner-take-all (WTA) circuits, where pyramidal neurons inhibit each other via interneurons, are a common motif of cortical microcircuits. We show through theoretical analysis and computer simulations that Bayesian computation is induced in these network motifs through STDP in combination with activity-dependent changes in the excitability of neurons. The fundamental components of this emergent Bayesian computation are priors that result from adaptation of neuronal excitability and implicit generative models for hidden causes that are created in the synaptic weights through STDP. In fact, a surprising result is that STDP is able to approximate a powerful principle for fitting such implicit generative models to high-dimensional spike inputs: Expectation Maximization. Our results suggest that the experimentally observed spontaneous activity and trial-to-trial variability of cortical neurons are essential features of their information processing capability, since their functional role is to represent probability distributions rather than static neural codes. Furthermore it suggests networks of Bayesian computation modules as a new model for distributed information processing in the cortex. PMID:23633941

Analysis of fluid-structure interaction in a frame pipe undergoing plastic deformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khamlichi, A.; Jezequel, L.; Jacques, Y.

1995-11-01

Water hammer pressure waves of sufficiently large magnitude can cause plastic flexural deformations in a frame pipe. In this study, the authors propose a modelization of this problem based on plane wave approximation for the fluid equations and approximation of the structure motion by a single-degree-of-freedom elastic-plastic oscillator. Direct analytical integration of elastic-plastic equations through pipe sections, then over the pipe length is performed in order to identify the oscillator parameters. Comparison of the global load-displacement relationship obtained with the finite element solution was considered and has shown good agreement. Fluid-structure coupling is achieved by assuming elbows to act likemore » plane monopole sources, where localized jumps of fluid velocity occur and where net pressure forces are exerted on the structure. The authors have applied this method to analyze the fluid-structure interaction in this range of deformations. Energy exchange between the fluid and the structure and energy dissipation are quantified.« less

Structural basis of divergent cyclin-dependent kinase activation by Spy1/RINGO proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGrath, Denise A.; Fifield, Bre‐Anne; Marceau, Aimee H.

Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. Spy1/RINGO (Spy1) proteins bind and activate Cdk but are resistant to canonical regulatory mechanisms that establish cell-cycle checkpoints. Cancer cells exploit Spy1 to stimulate proliferation through inappropriate activation of Cdks, yet the mechanism is unknown. We have determined crystal structures of the Cdk2-Spy1 and p27-Cdk2-Spy1 complexes that reveal how Spy1 activates Cdk. We find that Spy1 confers structural changesmore » to Cdk2 that obviate the requirement of Cdk activation loop phosphorylation. Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. We identify mutations in Spy1 that ablate its ability to activate Cdk2 and to proliferate cells. Our structural description of Spy1 provides important mechanistic insights that may be utilized for targeting upregulated Spy1 in cancer.« less

Biomolecule-assisted construction of cadmium sulfide hollow spheres with structure-dependent photocatalytic activity.

PubMed

Wei, Chengzhen; Zang, Wenzhe; Yin, Jingzhou; Lu, Qingyi; Chen, Qun; Liu, Rongmei; Gao, Feng

2013-02-25

In this study, we report the synthesis of monodispersive solid and hollow CdS spheres with structure-dependent photocatalytic abilities for dye photodegradation. The monodispersive CdS nanospheres were constructed with the assistance of the soulcarboxymthyi chitosan biopolymer under hydrothermal conditions. The solid CdS spheres were corroded by ammonia to form hollow CdS nanospheres through a dissolution-reprecipitation mechanism. Their visible-light photocatalytic activities were investigated, and the results show that both the solid and the hollow CdS spheres have visible-light photocatalytic abilities for the photodegradation of dyes. The photocatalytic properties of the CdS spheres were demonstrated to be structure dependent. Although the nanoparticles comprising the hollow spheres have larger sizes than those comprising the solid spheres, the hollow CdS spheres have better photocatalytic performances than the solid CdS spheres, which can be attributed to the special hollow structure. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Semantic modeling of the structural and process entities during plastic deformation of crystals and rocks

NASA Astrophysics Data System (ADS)

Babaie, Hassan; Davarpanah, Armita

2016-04-01

, spatial, temporal, statistical, and thermodynamical. The dynamical properties, categorized under the Dynamical_Rate_Property and Dynamical_State_Property classes, subsume different classes of properties (e.g., Fluid_Flow_Rate, Temperature, Chemical_Potential, Displacement, Electrical_Charge) based on the physical domain (e.g., fluid, heat, chemical, solid, electrical). The properties are related to the objects under the Physical_Entity class through diverse object type (e.g., physicalPropertyOf) and data type (e.g., Fluid_Pressure unit 'MPa') properties. The changes of the dynamical properties of the physical entities, described by the empirical laws (equations) modeled by experimental structural geologists, are modeled through the Physical_Property_Dependency class that subsumes the more specialized constitutive, kinetic, and thermodynamic expressions of the relationships among the dynamic properties. Annotation based on the PDO will make it possible to integrate and reuse experimental plastic deformation data, knowledge, and simulation models, and conduct semantic-based search of the source data originating from different rock testing laboratories.

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity

PubMed Central

Bennett, James E. M.; Bair, Wyeth

2015-01-01

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli. PMID:26308406

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity.

PubMed

Bennett, James E M; Bair, Wyeth

2015-08-01

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli.

Active-matrix OLED using 150°C a-Si TFT backplane built on flexible plastic substrate

NASA Astrophysics Data System (ADS)

Sarma, Kalluri R.; Chanley, Charles; Dodd, Sonia R.; Roush, Jared; Schmidt, John; Srdanov, Gordana; Stevenson, Matthew; Wessel, Ralf; Innocenzo, Jeffrey; Yu, Gang; O'Regan, Marie B.; MacDonald, W. A.; Eveson, R.; Long, Ke; Gleskova, Helena; Wagner, Sigurd; Sturm, James C.

2003-09-01

Flexible displays fabricated using plastic substrates have a potential for being very thin, light weight, highly rugged with greatly minimized propensity for breakage, roll-to-roll manufacturing and lower cost. The emerging OLED display media offers the advantage of being a solid state and rugged structure for flexible displays in addition to the many potential advantages of an AM OLED over the currently dominant AM LCD. The current high level of interest in flexible displays is facilitating the development of the required enabling technologies which include development of plastic substrates, low temperature active matrix device and backplane fabrication, and display packaging. In the following we will first discuss our development efforts in the PEN based plastic substrates, active matrix backplane technology, low temperature (150°C) a-Si TFT devices and an AM OLED test chip used for evaluating various candidate designs. We will then describe the design, fabrication and successful evaluation and demonstration of a 64x64 pixel AM OLED test display using a-Si TFT backplane fabricated at 150°C on the flexible plastic substrate.

NR2B-dependent plasticity of adult-born granule cells is necessary for context discrimination.

PubMed

Kheirbek, Mazen A; Tannenholz, Lindsay; Hen, René

2012-06-20

Adult-generated granule cells (GCs) in the dentate gyrus (DG) exhibit a period of heightened plasticity 4-6 weeks postmitosis. However, the functional contribution of this critical window of plasticity to hippocampal neurogenesis and behavior remains unknown. Here, we show that deletion of NR2B-containing NMDA receptors from adult-born GCs impairs a neurogenesis-dependent form of LTP in the DG and reduces dendritic complexity of adult-born GCs, but does not impact their survival. Mice in which the NR2B-containing NMDA receptor was deleted from adult-born GCs did not differ from controls in baseline anxiety-like behavior or discrimination of very different contexts, but were impaired in discrimination of highly similar contexts. These results indicate that NR2B-dependent plasticity of adult-born GCs is necessary for fine contextual discrimination and is consistent with their proposed role in pattern separation.

Structural Mechanism for the Temperature-Dependent Activation of the Hyperthermophilic Pf2001 Esterase.

PubMed

Varejão, Nathalia; De-Andrade, Rafael A; Almeida, Rodrigo V; Anobom, Cristiane D; Foguel, Debora; Reverter, David

2018-02-06

Lipases and esterases constitute a group of enzymes that catalyze the hydrolysis or synthesis of ester bonds. A major biotechnological interest corresponds to thermophilic esterases, due to their intrinsic stability at high temperatures. The Pf2001 esterase from Pyrococcus furiosus reaches its optimal activity between 70°C and 80°C. The crystal structure of the Pf2001 esterase shows two different conformations: monomer and dimer. The structures reveal important rearrangements in the "cap" subdomain between monomer and dimer, by the formation of an extensive intertwined helical interface. Moreover, the dimer interface is essential for the formation of the hydrophobic channel for substrate selectivity, as confirmed by mutagenesis and kinetic analysis. We also provide evidence for dimer formation at high temperatures, a process that correlates with its enzymatic activation. Thus, we propose a temperature-dependent activation mechanism of the Pf2001 esterase via dimerization that is necessary for the substrate channel formation in the active-site cleft. Copyright © 2017 Elsevier Ltd. All rights reserved.

Filopodia: A Rapid Structural Plasticity Substrate for Fast Learning

PubMed Central

Ozcan, Ahmet S.

2017-01-01

Formation of new synapses between neurons is an essential mechanism for learning and encoding memories. The vast majority of excitatory synapses occur on dendritic spines, therefore, the growth dynamics of spines is strongly related to the plasticity timescales. Especially in the early stages of the developing brain, there is an abundant number of long, thin and motile protrusions (i.e., filopodia), which develop in timescales of seconds and minutes. Because of their unique morphology and motility, it has been suggested that filopodia can have a dual role in both spinogenesis and environmental sampling of potential axonal partners. I propose that filopodia can lower the threshold and reduce the time to form new dendritic spines and synapses, providing a substrate for fast learning. Based on this proposition, the functional role of filopodia during brain development is discussed in relation to learning and memory. Specifically, it is hypothesized that the postnatal brain starts with a single-stage memory system with filopodia playing a significant role in rapid structural plasticity along with the stability provided by the mushroom-shaped spines. Following the maturation of the hippocampus, this highly-plastic unitary system transitions to a two-stage memory system, which consists of a plastic temporary store and a long-term stable store. In alignment with these architectural changes, it is posited that after brain maturation, filopodia-based structural plasticity will be preserved in specific areas, which are involved in fast learning (e.g., hippocampus in relation to episodic memory). These propositions aim to introduce a unifying framework for a diversity of phenomena in the brain such as synaptogenesis, pruning and memory consolidation. PMID:28676753

76 FR 175 - Continental Structural Plastics Including On-Site Leased Workers From Kelly Services and Time...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-03

... Plastics Including On-Site Leased Workers From Kelly Services and Time Staffing; North Baltimore, OH... Adjustment Assistance on December 31, 2008, applicable to workers of Continental Structural Plastics, North... Baltimore, Ohio location of Continental Structural Plastics. The Department has determined that these...

Ultrasound Velocity Measurements in High-Chromium Steel Under Plastic Deformation

NASA Astrophysics Data System (ADS)

Lunev, Aleksey; Bochkareva, Anna; Barannikova, Svetlana; Zuev, Lev

2016-04-01

In the present study, the variation of the propagation velocity of ultrasound in the plastic deformation of corrosion-resistant high-chromium steel 40X13 with ferrite-carbide (delivery status), martensitic (quenched) and sorbitol (after high-temperature tempering) structures have beem studied/ It is found that each state shows its view of the loading curve. In the delivery state diagram loading is substantially parabolic throughout, while in the martensitic state contains only linear strain hardening step and in the sorbitol state the plastic flow curve is three-step. The velocity of ultrasonic surface waves (Rayleigh waves) was measured simultaneously with the registration of the loading curve in the investigated steel in tension. It is shown that the dependence of the velocity of ultrasound in active loading is determined by the law of plastic flow, that is, the staging of the corresponding diagram of loading. Structural state of the investigated steel is not only changing the type of the deformation curve under uniaxial tension, but also changes the nature of ultrasound speed of deformation.

Glutamatergic plasticity and alcohol dependence-induced alterations in reward, affect and cognition.

PubMed

Burnett, Elizabeth J; Chandler, L Judson; Trantham-Davidson, Heather

2016-02-04

Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence. To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition. Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure. In particular, up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, this observation as well as other glutamatergic neuroadaptations are often circuit and cell-type specific. Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests that they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction. While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover novel, possibly circuit

A Novel, Simplified Scheme for Plastics Identification: "JCE" Classroom Activity 104

ERIC Educational Resources Information Center

Harris, Mary E.; Walker, Barbara

2010-01-01

In this Activity, students identify samples of seven types of recyclable plastic by using a flowchart scheme. The flowchart procedure includes making density comparisons of the plastic samples in water and alcohol and observing physical changes of plastic samples subjected to boiling water temperatures and exposure to acetone. This scheme is…

Presynaptic Active Zone Density during Development and Synaptic Plasticity.

PubMed

Clarke, Gwenaëlle L; Chen, Jie; Nishimune, Hiroshi

2012-01-01

Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated.

Presynaptic Active Zone Density during Development and Synaptic Plasticity

PubMed Central

Clarke, Gwenaëlle L.; Chen, Jie; Nishimune, Hiroshi

2012-01-01

Neural circuits transmit information through synapses, and the efficiency of synaptic transmission is closely related to the density of presynaptic active zones, where synaptic vesicles are released. The goal of this review is to highlight recent insights into the molecular mechanisms that control the number of active zones per presynaptic terminal (active zone density) during developmental and stimulus-dependent changes in synaptic efficacy. At the neuromuscular junctions (NMJs), the active zone density is preserved across species, remains constant during development, and is the same between synapses with different activities. However, the NMJ active zones are not always stable, as exemplified by the change in active zone density during acute experimental manipulation or as a result of aging. Therefore, a mechanism must exist to maintain its density. In the central nervous system (CNS), active zones have restricted maximal size, exist in multiple numbers in larger presynaptic terminals, and maintain a constant density during development. These findings suggest that active zone density in the CNS is also controlled. However, in contrast to the NMJ, active zone density in the CNS can also be increased, as observed in hippocampal synapses in response to synaptic plasticity. Although the numbers of known active zone proteins and protein interactions have increased, less is known about the mechanism that controls the number or spacing of active zones. The following molecules are known to control active zone density and will be discussed herein: extracellular matrix laminins and voltage-dependent calcium channels, amyloid precursor proteins, the small GTPase Rab3, an endocytosis mechanism including synaptojanin, cytoskeleton protein spectrins and β-adducin, and a presynaptic web including spectrins. The molecular mechanisms that organize the active zone density are just beginning to be elucidated. PMID:22438837

Learning Probabilistic Inference through Spike-Timing-Dependent Plasticity.

PubMed

Pecevski, Dejan; Maass, Wolfgang

2016-01-01

Numerous experimental data show that the brain is able to extract information from complex, uncertain, and often ambiguous experiences. Furthermore, it can use such learnt information for decision making through probabilistic inference. Several models have been proposed that aim at explaining how probabilistic inference could be performed by networks of neurons in the brain. We propose here a model that can also explain how such neural network could acquire the necessary information for that from examples. We show that spike-timing-dependent plasticity in combination with intrinsic plasticity generates in ensembles of pyramidal cells with lateral inhibition a fundamental building block for that: probabilistic associations between neurons that represent through their firing current values of random variables. Furthermore, by combining such adaptive network motifs in a recursive manner the resulting network is enabled to extract statistical information from complex input streams, and to build an internal model for the distribution p (*) that generates the examples it receives. This holds even if p (*) contains higher-order moments. The analysis of this learning process is supported by a rigorous theoretical foundation. Furthermore, we show that the network can use the learnt internal model immediately for prediction, decision making, and other types of probabilistic inference.

Structures of apicomplexan calcium-dependent protein kinases reveal mechanism of activation by calcium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wernimont, Amy K; Artz, Jennifer D.; Jr, Patrick Finerty

2010-09-21

Calcium-dependent protein kinases (CDPKs) have pivotal roles in the calcium-signaling pathway in plants, ciliates and apicomplexan parasites and comprise a calmodulin-dependent kinase (CaMK)-like kinase domain regulated by a calcium-binding domain in the C terminus. To understand this intramolecular mechanism of activation, we solved the structures of the autoinhibited (apo) and activated (calcium-bound) conformations of CDPKs from the apicomplexan parasites Toxoplasma gondii and Cryptosporidium parvum. In the apo form, the C-terminal CDPK activation domain (CAD) resembles a calmodulin protein with an unexpected long helix in the N terminus that inhibits the kinase domain in the same manner as CaMKII. Calcium bindingmore » triggers the reorganization of the CAD into a highly intricate fold, leading to its relocation around the base of the kinase domain to a site remote from the substrate binding site. This large conformational change constitutes a distinct mechanism in calcium signal-transduction pathways.« less

Plastics as structural materials for aircraft

NASA Technical Reports Server (NTRS)

Kline, G M

1937-01-01

The purpose here is to consider the mechanical characteristics of reinforced phenol-formaldehyde resin as related to its use as structural material for aircraft. Data and graphs that have appeared in the literature are reproduced to illustrate the comparative behavior of plastics and materials commonly used in aircraft construction. Materials are characterized as to density, static strength, modulus of elasticity, resistance to long-time loading, strength under repeated impact, energy absorption, corrosion resistance, and ease of fabrication.

76 FR 13227 - Continental Structural Plastics, Including On-Site Leased Workers From Kelly Services and Doepker...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-10

... Plastics, Including On-Site Leased Workers From Kelly Services and Doepker Group, Inc., Formerly Known As... Continental Structural Plastics, North Baltimore, Ohio. The workers produce exterior body panels and under... to TA-W-64,458 is hereby issued as follows: All workers of Continental Structural Plastics, including...

Structural and synaptic plasticity in stress-related disorders

PubMed Central

Christoffel, Daniel J.; Golden, Sam A.; Russo, Scott J.

2011-01-01

Stress can have a lasting impact on the structure and function of brain circuitry that results in long-lasting changes in the behavior of an organism. Synaptic plasticity is the mechanism by which information is stored and maintained within individual synapses, neurons, and neuronal circuits to guide the behavior of an organism. Although these mechanisms allow the organism to adapt to its constantly evolving environment, not all of these adaptations are beneficial. Under prolonged bouts of physical or psychological stress, these mechanisms become dysregulated, and the connectivity between brain regions becomes unbalanced, resulting in pathological behaviors. In this review, we highlight the effects of stress on the structure and function of neurons within the mesocorticolimbic brain systems known to regulate mood and motivation. We then discuss the implications of these spine adaptations on neuronal activity and pathological behaviors implicated in mood disorders. Finally, we end by discussing recent brain imaging studies in human depression within the context of these basic findings to provide insight into the underlying mechanisms leading to neural dysfunction in depression. PMID:21967517

Dissolved organic carbon leaching from plastics stimulates microbial activity in the ocean.

PubMed

Romera-Castillo, Cristina; Pinto, Maria; Langer, Teresa M; Álvarez-Salgado, Xosé Antón; Herndl, Gerhard J

2018-04-12

Approximately 5.25 trillion plastic pieces are floating at the sea surface. The impact of plastic pollution on the lowest trophic levels of the food web, however, remains unknown. Here we show that plastics release dissolved organic carbon (DOC) into the ambient seawater stimulating the activity of heterotrophic microbes. Our estimates indicate that globally up to 23,600 metric tons of DOC are leaching from marine plastics annually. About 60% of it is available to microbial utilization in less than 5 days. If exposed to solar radiation, however, this DOC becomes less labile. Thus, plastic pollution of marine surface waters likely alters the composition and activity of the base of the marine food webs. It is predicted that plastic waste entering the ocean will increase by a factor of ten within the next decade, resulting in an increase in plastic-derived DOC that might have unaccounted consequences for marine microbes and for the ocean system.

Epigenetic Basis of Neuronal and Synaptic Plasticity.

PubMed

Karpova, Nina N; Sales, Amanda J; Joca, Samia R

2017-01-01

Neuronal network and plasticity change as a function of experience. Altered neural connectivity leads to distinct transcriptional programs of neuronal plasticity-related genes. The environmental challenges throughout life may promote long-lasting reprogramming of gene expression and the development of brain disorders. The modifications in neuronal epigenome mediate gene-environmental interactions and are required for activity-dependent regulation of neuronal differentiation, maturation and plasticity. Here, we highlight the latest advances in understanding the role of the main players of epigenetic machinery (DNA methylation and demethylation, histone modifications, chromatin-remodeling enzymes, transposons, and non-coding RNAs) in activity-dependent and long- term neural and synaptic plasticity. The review focuses on both the transcriptional and post-transcriptional regulation of gene expression levels, including the processes of promoter activation, alternative splicing, regulation of stability of gene transcripts by natural antisense RNAs, and alternative polyadenylation. Further, we discuss the epigenetic aspects of impaired neuronal plasticity and the pathogenesis of neurodevelopmental (Rett syndrome, Fragile X Syndrome, genomic imprinting disorders, schizophrenia, and others), stressrelated (mood disorders) and neurodegenerative Alzheimer's, Parkinson's and Huntington's disorders. The review also highlights the pharmacological compounds that modulate epigenetic programming of gene expression, the potential treatment strategies of discussed brain disorders, and the questions that should be addressed during the development of effective and safe approaches for the treatment of brain disorders.

Background sounds contribute to spectrotemporal plasticity in primary auditory cortex.

PubMed

Moucha, Raluca; Pandya, Pritesh K; Engineer, Navzer D; Rathbun, Daniel L; Kilgard, Michael P

2005-05-01

The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8-4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity.

Background sounds contribute to spectrotemporal plasticity in primary auditory cortex

PubMed Central

Moucha, Raluca; Pandya, Pritesh K.; Engineer, Navzer D.; Rathbun, Daniel L.

2010-01-01

The mammalian auditory system evolved to extract meaningful information from complex acoustic environments. Spectrotemporal selectivity of auditory neurons provides a potential mechanism to represent natural sounds. Experience-dependent plasticity mechanisms can remodel the spectrotemporal selectivity of neurons in primary auditory cortex (A1). Electrical stimulation of the cholinergic nucleus basalis (NB) enables plasticity in A1 that parallels natural learning and is specific to acoustic features associated with NB activity. In this study, we used NB stimulation to explore how cortical networks reorganize after experience with frequency-modulated (FM) sweeps, and how background stimuli contribute to spectrotemporal plasticity in rat auditory cortex. Pairing an 8–4 kHz FM sweep with NB stimulation 300 times per day for 20 days decreased tone thresholds, frequency selectivity, and response latency of A1 neurons in the region of the tonotopic map activated by the sound. In an attempt to modify neuronal response properties across all of A1 the same NB activation was paired in a second group of rats with five downward FM sweeps, each spanning a different octave. No changes in FM selectivity or receptive field (RF) structure were observed when the neural activation was distributed across the cortical surface. However, the addition of unpaired background sweeps of different rates or direction was sufficient to alter RF characteristics across the tonotopic map in a third group of rats. These results extend earlier observations that cortical neurons can develop stimulus specific plasticity and indicate that background conditions can strongly influence cortical plasticity PMID:15616812

Neuronal avalanches of a self-organized neural network with active-neuron-dominant structure.

PubMed

Li, Xiumin; Small, Michael

2012-06-01

Neuronal avalanche is a spontaneous neuronal activity which obeys a power-law distribution of population event sizes with an exponent of -3/2. It has been observed in the superficial layers of cortex both in vivo and in vitro. In this paper, we analyze the information transmission of a novel self-organized neural network with active-neuron-dominant structure. Neuronal avalanches can be observed in this network with appropriate input intensity. We find that the process of network learning via spike-timing dependent plasticity dramatically increases the complexity of network structure, which is finally self-organized to be active-neuron-dominant connectivity. Both the entropy of activity patterns and the complexity of their resulting post-synaptic inputs are maximized when the network dynamics are propagated as neuronal avalanches. This emergent topology is beneficial for information transmission with high efficiency and also could be responsible for the large information capacity of this network compared with alternative archetypal networks with different neural connectivity.

Mirror trends of plasticity and stability indicators in primate prefrontal cortex.

PubMed

García-Cabezas, Miguel Á; Joyce, Mary Kate P; John, Yohan J; Zikopoulos, Basilis; Barbas, Helen

2017-10-01

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here, we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity-related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

PubMed Central

Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

2012-01-01

Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID

Principles of Experience-Dependent Neural Plasticity: Implications for Rehabilitation after Brain Damage

ERIC Educational Resources Information Center

Kleim, Jeffrey A.; Jones, Theresa A.

2008-01-01

Purpose: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. Method: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the…

PLCγ-activated signalling is essential for TrkB mediated sensory neuron structural plasticity

PubMed Central

2010-01-01

Background The vestibular system provides the primary input of our sense of balance and spatial orientation. Dysfunction of the vestibular system can severely affect a person's quality of life. Therefore, understanding the molecular basis of vestibular neuron survival, maintenance, and innervation of the target sensory epithelia is fundamental. Results Here we report that a point mutation at the phospholipase Cγ (PLCγ) docking site in the mouse neurotrophin tyrosine kinase receptor TrkB (Ntrk2) specifically impairs fiber guidance inside the vestibular sensory epithelia, but has limited effects on the survival of vestibular sensory neurons and growth of afferent processes toward the sensory epithelia. We also show that expression of the TRPC3 cation calcium channel, whose activity is known to be required for nerve-growth cone guidance induced by brain-derived neurotrophic factor (BDNF), is altered in these animals. In addition, we find that absence of the PLCγ mediated TrkB signalling interferes with the transformation of bouton type afferent terminals of vestibular dendrites into calyces (the largest synaptic contact of dendrites known in the mammalian nervous system) on type I vestibular hair cells; the latter are normally distributed in these mutants as revealed by an unaltered expression pattern of the potassium channel KCNQ4 in these cells. Conclusions These results demonstrate a crucial involvement of the TrkB/PLCγ-mediated intracellular signalling in structural aspects of sensory neuron plasticity. PMID:20932311

Significance of Objective Structured Clinical Examinations to Plastic Surgery Residency Training.

PubMed

Simmons, Brian J; Zoghbi, Yasmina; Askari, Morad; Birnbach, David J; Shekhter, Ilya; Thaller, Seth R

2017-09-01

Objective structured clinical examinations (OSCEs) have proven to be a powerful tool. They possess more than a 30-year track record in assessing the competency of medical students, residents, and fellows. Objective structured clinical examinations have been used successfully in a variety of medical specialties, including surgery. They have recently found their way into the subspecialty of plastic surgery. This article uses a systematic review of the available literature on OSCEs and their recent use in plastic surgery. It incorporates survey results assessing program directors' views on the use of OSCEs. Approximately 40% of programs surveyed use OSCEs to assess the Accreditation Council for Graduate Medical Education core competencies. We found that 40% use OSCEs to evaluate specific plastic surgery milestones. Objective structured clinical examinations are usually performed annually. They cost anywhere between $100 and more than $1000 per resident. Four milestones giving residents the most difficulties on OSCEs were congenital anomalies, noncancer breast surgery, breast reconstruction, and practice-based learning and improvement. It was determined that challenges with milestones were due to lack of adequate general knowledge and surgical ward patient care, as well as deficits in professionalism and system-based problems. Programs were able to remediate weakness found by OSCEs using a variety of methods. Objective structured clinical examinations offer a unique tool to objectively assess the proficiency of residents in key areas of the Accreditation Council for Graduate Medical Education core competencies. In addition, they can be used to assess the specific milestones that plastic surgery residents must meet. This allows programs to identify and improve identified areas of weakness.

Structural plasticity in the language system related to increased second language proficiency.

PubMed

Stein, Maria; Federspiel, Andrea; Koenig, Thomas; Wirth, Miranka; Strik, Werner; Wiest, Roland; Brandeis, Daniel; Dierks, Thomas

2012-04-01

While functional changes linked to second language learning have been subject to extensive investigation, the issue of learning-dependent structural plasticity in the fields of bilingualism and language comprehension has so far received less notice. In the present study we used voxel-based morphometry to monitor structural changes occurring within five months of second language learning. Native English-speaking exchange students learning German in Switzerland were examined once at the beginning of their stay and once about five months later, when their German language skills had significantly increased. We show that structural changes in the left inferior frontal gyrus are correlated with the increase in second language proficiency as measured by a paper-and-pencil language test. Contrary to the increase in proficiency and grey matter, the absolute values of grey matter density and second language proficiency did not correlate (neither on first nor on second measurement). This indicates that the individual amount of learning is reflected in brain structure changes, regardless of absolute proficiency. Copyright © 2010 Elsevier Srl. All rights reserved.

Repeated Structural Imaging Reveals Nonlinear Progression of Experience-Dependent Volume Changes in Human Motor Cortex.

PubMed

Wenger, Elisabeth; Kühn, Simone; Verrel, Julius; Mårtensson, Johan; Bodammer, Nils Christian; Lindenberger, Ulman; Lövdén, Martin

2017-05-01

Evidence for experience-dependent structural brain change in adult humans is accumulating. However, its time course is not well understood, as intervention studies typically consist of only 2 imaging sessions (before vs. after training). We acquired up to 18 structural magnetic resonance images over a 7-week period while 15 right-handed participants practiced left-hand writing and drawing. After 4 weeks, we observed increases in gray matter of both left and right primary motor cortices relative to a control group; 3 weeks later, these differences were no longer reliable. Time-series analyses revealed that gray matter in the primary motor cortices expanded during the first 4 weeks and then partially renormalized, in particular in the right hemisphere, despite continued practice and increasing task proficiency. Similar patterns of expansion followed by partial renormalization are also found in synaptogenesis, cortical map plasticity, and maturation, and may qualify as a general principle of structural plasticity. Research on human brain plasticity needs to encompass more than 2 measurement occasions to capture expansion and potential renormalization processes over time. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

High-Aspect-Ratio Ridge Structures Induced by Plastic Deformation as a Novel Microfabrication Technique.

PubMed

Takei, Atsushi; Jin, Lihua; Fujita, Hiroyuki; Takei, A; Fujita, H; Jin, Lihua

2016-09-14

Wrinkles on thin film/elastomer bilayer systems provide functional surfaces. The aspect ratio of these wrinkles is critical to their functionality. Much effort has been dedicated to creating high-aspect-ratio structures on the surface of bilayer systems. A highly prestretched elastomer attached to a thin film has recently been shown to form a high-aspect-ratio structure, called a ridge structure, due to a large strain induced in the elastomer. However, the prestretch requirements of the elastomer during thin film attachment are not compatible with conventional thin film deposition methods, such as spin coating, dip coating, and chemical vapor deposition (CVD). Thus, the fabrication method is complex, and ridge structure formation is limited to planar surfaces. This paper presents a new and simple method for constructing ridge structures on a nonplanar surface using a plastic thin film/elastomer bilayer system. A plastic thin film is attached to a stress-free elastomer, and the resulting bilayer system is highly stretched one- or two-dimensionally. Upon the release of the stretch load, the deformation of the elastomer is reversible, while the plastically deformed thin film stays elongated. The combination of the length mismatch and the large strain induced in the elastomer generates ridge structures. The morphology of the plastic thin film/elastomer bilayer system is experimentally studied by varying the physical parameters, and the functionality and the applicability to a nonplanar surface are demonstrated. Finally, we simulate the effect of plasticity on morphology. This study presents a new technique for generating microscale high-aspect-ratio structures and its potential for functional surfaces.

Application of an Elastic-Plastic Methodology to Structural Integrity Evaluation,

DTIC Science & Technology

The elastic plastic fracture mechanics ( EPFM ) technology has advanced to the point where it can be used to make a realistic assessment of the...concepts of EPFM into a structural stability evaluation. The structure is modeled as a cracked test specimen either in series or parallel with a spring

Model-Driven Analysis of Eyeblink Classical Conditioning Reveals the Underlying Structure of Cerebellar Plasticity and Neuronal Activity.

PubMed

Antonietti, Alberto; Casellato, Claudia; D'Angelo, Egidio; Pedrocchi, Alessandra

The cerebellum plays a critical role in sensorimotor control. However, how the specific circuits and plastic mechanisms of the cerebellum are engaged in closed-loop processing is still unclear. We developed an artificial sensorimotor control system embedding a detailed spiking cerebellar microcircuit with three bidirectional plasticity sites. This proved able to reproduce a cerebellar-driven associative paradigm, the eyeblink classical conditioning (EBCC), in which a precise time relationship between an unconditioned stimulus (US) and a conditioned stimulus (CS) is established. We challenged the spiking model to fit an experimental data set from human subjects. Two subsequent sessions of EBCC acquisition and extinction were recorded and transcranial magnetic stimulation (TMS) was applied on the cerebellum to alter circuit function and plasticity. Evolutionary algorithms were used to find the near-optimal model parameters to reproduce the behaviors of subjects in the different sessions of the protocol. The main finding is that the optimized cerebellar model was able to learn to anticipate (predict) conditioned responses with accurate timing and success rate, demonstrating fast acquisition, memory stabilization, rapid extinction, and faster reacquisition as in EBCC in humans. The firing of Purkinje cells (PCs) and deep cerebellar nuclei (DCN) changed during learning under the control of synaptic plasticity, which evolved at different rates, with a faster acquisition in the cerebellar cortex than in DCN synapses. Eventually, a reduced PC activity released DCN discharge just after the CS, precisely anticipating the US and causing the eyeblink. Moreover, a specific alteration in cortical plasticity explained the EBCC changes induced by cerebellar TMS in humans. In this paper, for the first time, it is shown how closed-loop simulations, using detailed cerebellar microcircuit models, can be successfully used to fit real experimental data sets. Thus, the changes of the

Fusion activity of HIV gp41 fusion domain is related to its secondary structure and depth of membrane insertion in a cholesterol-dependent fashion.

PubMed

Lai, Alex L; Moorthy, Anna Eswara; Li, Yinling; Tamm, Lukas K

2012-04-20

The human immunodeficiency virus (HIV) gp41 fusion domain plays a critical role in membrane fusion during viral entry. A thorough understanding of the relationship between the structure and the activity of the fusion domain in different lipid environments helps to formulate mechanistic models on how it might function in mediating membrane fusion. The secondary structure of the fusion domain in small liposomes composed of different lipid mixtures was investigated by circular dichroism spectroscopy.  The fusion domain formed an α-helix in membranes containing less than 30 mol% cholesterol and  formed β-sheet secondary structure in membranes containing ≥30 mol% cholesterol. EPR spectra of spin-labeled fusion domains also indicated different conformations in membranes with and without cholesterol. Power saturation EPR data were further used to determine the orientation and depth of α-helical fusion domains in lipid bilayers. Fusion and membrane perturbation activities of the gp41 fusion domain were measured by lipid mixing and contents leakage. The fusion domain fused membranes in both its helical form and its β-sheet form. High cholesterol, which induced β-sheets, promoted fusion; however, acidic lipids, which promoted relatively deep membrane insertion as an α-helix, also induced fusion. The results indicate that the structure of the HIV gp41 fusion domain is plastic and depends critically on the lipid environment. Provided that their membrane insertion is deep, α-helical and β-sheet conformations contribute to membrane fusion. Copyright © 2012 Elsevier Ltd. All rights reserved.

Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity

PubMed Central

Admon, Roee; Lubin, Gad; Stern, Orit; Rosenberg, Keren; Sela, Lee; Ben-Ami, Haim; Hendler, Talma

2009-01-01

Variations in people's vulnerability to stressful life events may rise from a predated neural sensitivity as well as from differential neural modifications in response to the event. Because the occurrence of a stressful life event cannot be foreseen, characterizing the temporal trajectory of its neural manifestations in humans has been a real challenge. The current prospective study examined the emotional experience and brain responses of 50 a priori healthy new recruits to the Israeli Defense Forces at 2 time points: before they entered their mandatory military service and after their subsequent exposure to stressful events while deployed in combat units. Over time, soldiers reported on increase in stress symptoms that was correlated with greater amygdala and hippocampus responsiveness to stress-related content. However, these closely situated core limbic regions exhibited different temporal trajectories with regard to the stress effect; whereas amygdala's reactivity before stress predicted the increase in stress symptoms, the hippocampal change in activation over time correlated with the increase in such symptoms. Hippocampal plasticity was also reflected by a modification over time of its functional coupling with the ventromedial prefrontal cortex, and this coupling magnitude was again predicted by predated amygdala reactivity. Together, these findings suggest that variations in human's likelihood to develop symptomatic phenomena following stressful life events may depend on a balanced interplay between their amygdala's predisposing reactivity and hippocampal posteriori intra- and interregional plasticity. Accordingly, an individually tailored therapeutic approach for trauma survivors should target these 2 neural probes while considering their unique temporal prints. PMID:19666562

Structural Transformations in Metallic Materials During Plastic Deformation

NASA Astrophysics Data System (ADS)

Zasimchuk, E.; Turchak, T.; Baskova, A.; Chausov, N.; Hutsaylyuk, V.

2017-03-01

In this paper, the structure formation during the plastic deformation of polycrystalline nickel and aluminum based alloy 2024-T3 is investigated. The possibility of the relaxation and synergetic structure formation is examined. It is shown the deformation softening to be due to the crystallization of the amorphous structure of hydrodynamics flow channels (synergetic structure) HC as micrograins and their subsequent growth. The possible mechanism of micrograins' growth is proposed. The deformation processes change the phase composition of the multiphase alloy 2024-T3. It is shown by the quantitative analysis of the structures which were deformed in different regimes of the alloy samples. A method for increasing of the fatigue life through a dynamic pre-deformation is suggested.

Synaptic Scaling in Combination with Many Generic Plasticity Mechanisms Stabilizes Circuit Connectivity

PubMed Central

Tetzlaff, Christian; Kolodziejski, Christoph; Timme, Marc; Wörgötter, Florentin

2011-01-01

Synaptic scaling is a slow process that modifies synapses, keeping the firing rate of neural circuits in specific regimes. Together with other processes, such as conventional synaptic plasticity in the form of long term depression and potentiation, synaptic scaling changes the synaptic patterns in a network, ensuring diverse, functionally relevant, stable, and input-dependent connectivity. How synaptic patterns are generated and stabilized, however, is largely unknown. Here we formally describe and analyze synaptic scaling based on results from experimental studies and demonstrate that the combination of different conventional plasticity mechanisms and synaptic scaling provides a powerful general framework for regulating network connectivity. In addition, we design several simple models that reproduce experimentally observed synaptic distributions as well as the observed synaptic modifications during sustained activity changes. These models predict that the combination of plasticity with scaling generates globally stable, input-controlled synaptic patterns, also in recurrent networks. Thus, in combination with other forms of plasticity, synaptic scaling can robustly yield neuronal circuits with high synaptic diversity, which potentially enables robust dynamic storage of complex activation patterns. This mechanism is even more pronounced when considering networks with a realistic degree of inhibition. Synaptic scaling combined with plasticity could thus be the basis for learning structured behavior even in initially random networks. PMID:22203799

Mechanical and time-dependent behavior of wood-plastic composites subjected to bending

Treesearch

S. E. Hamel; John Hermanson; S. M. Cramer

2015-01-01

The most popular use of wood–plastic composite (WPC) members in the United States has been as outdoor decking material in residential construction. If the use of these products expands into more structural applications, such as beams and joists, it is imperative that the material’s mechanical behavior be understood. Since most of the potential structural uses of this...

Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury

PubMed Central

McPherson, Jacob G.; Miller, Robert R.; Perlmutter, Steve I.

2015-01-01

Use-dependent movement therapies can lead to partial recovery of motor function after neurological injury. We attempted to improve recovery by developing a neuroprosthetic intervention that enhances movement therapy by directing spike timing-dependent plasticity in spared motor pathways. Using a recurrent neural–computer interface in rats with a cervical contusion of the spinal cord, we synchronized intraspinal microstimulation below the injury with the arrival of functionally related volitional motor commands signaled by muscle activity in the impaired forelimb. Stimulation was delivered during physical retraining of a forelimb behavior and throughout the day for 3 mo. Rats receiving this targeted, activity-dependent spinal stimulation (TADSS) exhibited markedly enhanced recovery compared with animals receiving targeted but open-loop spinal stimulation and rats receiving physical retraining alone. On a forelimb reach and grasp task, TADSS animals recovered 63% of their preinjury ability, more than two times the performance level achieved by the other therapy groups. Therapeutic gains were maintained for 3 additional wk without stimulation. The results suggest that activity-dependent spinal stimulation can induce neural plasticity that improves behavioral recovery after spinal cord injury. PMID:26371306

Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model.

PubMed

Lim, Chae-Seok; Hoang, Elizabeth T; Viar, Kenneth E; Stornetta, Ruth L; Scott, Michael M; Zhu, J Julius

2014-02-01

Fragile X syndrome, caused by the loss of Fmr1 gene function, is the most common form of inherited mental retardation, with no effective treatment. Using a tractable animal model, we investigated mechanisms of action of a few FDA-approved psychoactive drugs that modestly benefit the cognitive performance in fragile X patients. Here we report that compounds activating serotonin (5HT) subtype 2B receptors (5HT2B-Rs) or dopamine (DA) subtype 1-like receptors (D1-Rs) and/or those inhibiting 5HT2A-Rs or D2-Rs moderately enhance Ras-PI3K/PKB signaling input, GluA1-dependent synaptic plasticity, and learning in Fmr1 knockout mice. Unexpectedly, combinations of these 5HT and DA compounds at low doses synergistically stimulate Ras-PI3K/PKB signal transduction and GluA1-dependent synaptic plasticity and remarkably restore normal learning in Fmr1 knockout mice without causing anxiety-related side effects. These findings suggest that properly dosed and combined FDA-approved psychoactive drugs may effectively treat the cognitive impairment associated with fragile X syndrome.

Nonlinear dielectric spectroscopy in a fragile plastic crystal

NASA Astrophysics Data System (ADS)

Michl, M.; Bauer, Th.; Lunkenheimer, P.; Loidl, A.

2016-03-01

In this work we provide a thorough examination of the nonlinear dielectric properties of a succinonitrile-glutaronitrile mixture, representing one of the rare examples of a plastic crystal with fragile glassy dynamics. The detected alteration of the complex dielectric permittivity under high fields can be explained considering the heterogeneous nature of glassy dynamics and a field-induced variation of entropy. While the first mechanism was also found in structural glass formers, the latter effect seems to be more pronounced in plastic crystals. Moreover, the third harmonic component of the dielectric susceptibility is reported, revealing a hump-like spectral shape as predicted, e.g., within a model considering cooperative molecular dynamics. If assuming the validity of this model, one can deduce the temperature dependence of the number of correlated molecules Ncorr from these data. In accord with the fragile nature of the glass transition in this plastic crystal, we obtain a relatively strong temperature dependence of Ncorr, in contrast to the much weaker temperature dependence in plastic-crystalline cyclo-octanol, whose glass transition is of strong nature.

Plastics in Our Environment: A Jigsaw Learning Activity

ERIC Educational Resources Information Center

Hampton, Elaine; Wallace, Mary Ann; Lee, Wen-Yee

2009-01-01

In this lesson, a ready-to-teach cooperative reading activity, students learn about the effects of plastics in our environment, specifically that certain petrochemicals act as artificial estrogens and impact hormonal activities. Much of the content in this lesson was synthesized from recent medical research about the impact of xenoestrogens and…

Demonstrating the Effects of Processing on the Structure and Physical Properties of Plastic Using Disposable PETE Cups

ERIC Educational Resources Information Center

Erk, Kendra A.; Rhein, Morgan; Krafcik, Matthew J.; Ydstie, Sophie

2015-01-01

An educational activity is described in which the structure and physical properties of disposable plastic cups were directly related to the method of processing. The mechanical properties of specimens cut from the walls of poly(ethylene terephthalate) (PETE) cups, oriented parallel and perpendicular to the thermoforming direction, were measured in…

Myosin IIb-dependent Regulation of Actin Dynamics Is Required for N-Methyl-D-aspartate Receptor Trafficking during Synaptic Plasticity.

PubMed

Bu, Yunfei; Wang, Ning; Wang, Shaoli; Sheng, Tao; Tian, Tian; Chen, Linlin; Pan, Weiwei; Zhu, Minsheng; Luo, Jianhong; Lu, Wei

2015-10-16

N-Methyl-d-aspartate receptor (NMDAR) synaptic incorporation changes the number of NMDARs at synapses and is thus critical to various NMDAR-dependent brain functions. To date, the molecules involved in NMDAR trafficking and the underlying mechanisms are poorly understood. Here, we report that myosin IIb is an essential molecule in NMDAR synaptic incorporation during PKC- or θ burst stimulation-induced synaptic plasticity. Moreover, we demonstrate that myosin light chain kinase (MLCK)-dependent actin reorganization contributes to NMDAR trafficking. The findings from additional mutual occlusion experiments demonstrate that PKC and MLCK share a common signaling pathway in NMDAR-mediated synaptic regulation. Because myosin IIb is the primary substrate of MLCK and can regulate actin dynamics during synaptic plasticity, we propose that the MLCK- and myosin IIb-dependent regulation of actin dynamics is required for NMDAR trafficking during synaptic plasticity. This study provides important insights into a mechanical framework for understanding NMDAR trafficking associated with synaptic plasticity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Evidence for structural plasticity in humans: comment on Thomas and Baker (2012).

PubMed

Erickson, Kirk I

2013-06-01

Thomas and Baker (2012) have provided a balanced and critical review of the scientific evidence claiming that training interventions have the capacity to alter the structural morphology of the brain. Here I provide some additional considerations when reading and interpreting both the review and the original empirical articles. Research proposing to examine the capacity for structural brain plasticity needs to contemplate methodological issues and factors that could moderate or mask potentially interesting effects. Overall, although this area of research is in need of circumspection, it also could have transformative implications if structural brain plasticity in humans is possible. Copyright © 2012 Elsevier Inc. All rights reserved.

The expression of plasticity-related genes in an acute model of stress is modulated by chronic desipramine in a time-dependent manner within medial prefrontal cortex.

PubMed

Nava, Nicoletta; Treccani, Giulia; Müller, Heidi Kaastrup; Popoli, Maurizio; Wegener, Gregers; Elfving, Betina

2017-01-01

It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI). In the present study we evaluated the effects of acute Foot-shock (FS)-stress and pre-treatment with the traditional antidepressant DMI on the gene expression of key regulators of synaptic plasticity and structure. Expression of Homer, Shank, Spinophilin, Densin-180, and the small RhoGTPase related gene Rac1 and downstream target genes, Limk1, Cofilin1 and Rock1 were investigated 1 day (1d), 7 d and 14d after FS-stress exposure. We found that DMI specifically increases the short-term expression of Spinophilin, as well as Homer and Shank family genes, and that both acute stress and DMI exert significant long-term effects on mRNA levels of genes involved in spine plasticity. These findings support the knowledge that acute FS stress and antidepressant treatment induce both rapid and sustained time-dependent alterations in structural components of synaptic plasticity in rodent medial PFC. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Phyllosphere yeasts rapidly break down biodegradable plastics

PubMed Central

2011-01-01

The use of biodegradable plastics can reduce the accumulation of environmentally persistent plastic wastes. The rate of degradation of biodegradable plastics depends on environmental conditions and is highly variable. Techniques for achieving more consistent degradation are needed. However, only a few microorganisms involved in the degradation process have been isolated so far from the environment. Here, we show that Pseudozyma spp. yeasts, which are common in the phyllosphere and are easily isolated from plant surfaces, displayed strong degradation activity on films made from poly-butylene succinate or poly-butylene succinate-co-adipate. Strains of P. antarctica isolated from leaves and husks of paddy rice displayed strong degradation activity on these films at 30°C. The type strain, P. antarctica JCM 10317, and Pseudozyma spp. strains from phyllosphere secreted a biodegradable plastic-degrading enzyme with a molecular mass of about 22 kDa. Reliable source of biodegradable plastic-degrading microorganisms are now in our hands. PMID:22126328

Phyllosphere yeasts rapidly break down biodegradable plastics.

PubMed

Kitamoto, Hiroko K; Shinozaki, Yukiko; Cao, Xiao-Hong; Morita, Tomotake; Konishi, Masaaki; Tago, Kanako; Kajiwara, Hideyuki; Koitabashi, Motoo; Yoshida, Shigenobu; Watanabe, Takashi; Sameshima-Yamashita, Yuka; Nakajima-Kambe, Toshiaki; Tsushima, Seiya

2011-11-29

The use of biodegradable plastics can reduce the accumulation of environmentally persistent plastic wastes. The rate of degradation of biodegradable plastics depends on environmental conditions and is highly variable. Techniques for achieving more consistent degradation are needed. However, only a few microorganisms involved in the degradation process have been isolated so far from the environment. Here, we show that Pseudozyma spp. yeasts, which are common in the phyllosphere and are easily isolated from plant surfaces, displayed strong degradation activity on films made from poly-butylene succinate or poly-butylene succinate-co-adipate. Strains of P. antarctica isolated from leaves and husks of paddy rice displayed strong degradation activity on these films at 30°C. The type strain, P. antarctica JCM 10317, and Pseudozyma spp. strains from phyllosphere secreted a biodegradable plastic-degrading enzyme with a molecular mass of about 22 kDa. Reliable source of biodegradable plastic-degrading microorganisms are now in our hands.

Gap junction plasticity as a mechanism to regulate network-wide oscillations

PubMed Central

Nicola, Wilten; Clopath, Claudia

2018-01-01

Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex. We developed a computational model of gap junction plasticity in a recurrent cortical network based on recent experimental findings. We showed that gap junction plasticity can serve as a homeostatic mechanism for oscillations by maintaining a tight balance between two network states: asynchronous irregular activity and synchronized oscillations. This homeostatic mechanism allows for robust communication between neuronal assemblies through two different mechanisms: transient oscillations and frequency modulation. This implies a direct functional role for gap junction plasticity in information transmission in cortex. PMID:29529034

Study on Collision of Ship Side Structure by Simplified Plastic Analysis Method

NASA Astrophysics Data System (ADS)

Sun, C. J.; Zhou, J. H.; Wu, W.

2017-10-01

During its lifetime, a ship may encounter collision or grounding and sustain permanent damage after these types of accidents. Crashworthiness has been based on two kinds of main methods: simplified plastic analysis and numerical simulation. A simplified plastic analysis method is presented in this paper. Numerical methods using the non-linear finite-element software LS-DYNA are conducted to validate the method. The results show that, as for the accuracy of calculation results, the simplified plasticity analysis are in good agreement with the finite element simulation, which reveals that the simplified plasticity analysis method can quickly and accurately estimate the crashworthiness of the side structure during the collision process and can be used as a reliable risk assessment method.

SorCS2 is required for BDNF-dependent plasticity in the hippocampus.

PubMed

Glerup, S; Bolcho, U; Mølgaard, S; Bøggild, S; Vaegter, C B; Smith, A H; Nieto-Gonzalez, J L; Ovesen, P L; Pedersen, L F; Fjorback, A N; Kjolby, M; Login, H; Holm, M M; Andersen, O M; Nyengaard, J R; Willnow, T E; Jensen, K; Nykjaer, A

2016-12-01

SorCS2 is a member of the Vps10p-domain receptor gene family receptors with critical roles in the control of neuronal viability and function. Several genetic studies have suggested SORCS2 to confer risk of bipolar disorder, schizophrenia and attention deficit-hyperactivity disorder. Here we report that hippocampal N-methyl-d-aspartate receptor-dependent synaptic plasticity is eliminated in SorCS2-deficient mice. This defect was traced to the ability of SorCS2 to form complexes with the neurotrophin receptor p75 NTR , required for pro-brain-derived neurotrophic factor (BDNF) to induce long-term depression, and with the BDNF receptor tyrosine kinase TrkB to elicit long-term potentiation. Although the interaction with p75 NTR was static, SorCS2 bound to TrkB in an activity-dependent manner to facilitate its translocation to postsynaptic densities for synaptic tagging and maintenance of synaptic potentiation. Neurons lacking SorCS2 failed to respond to BDNF by TrkB autophosphorylation, and activation of downstream signaling cascades, impacting neurite outgrowth and spine formation. Accordingly, Sorcs2 -/- mice displayed impaired formation of long-term memory, increased risk taking and stimulus seeking behavior, enhanced susceptibility to stress and impaired prepulse inhibition. Our results identify SorCS2 as an indispensable coreceptor for p75 NTR and TrkB in hippocampal neurons and suggest SORCS2 as the link between proBDNF/BDNF signaling and mental disorders.

Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

PubMed Central

Phan, Mimi L.; Bieszczad, Kasia M.

2016-01-01

Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded. PMID:26881129

Enabling Functional Neural Circuit Simulations with Distributed Computing of Neuromodulated Plasticity

PubMed Central

Potjans, Wiebke; Morrison, Abigail; Diesmann, Markus

2010-01-01

A major puzzle in the field of computational neuroscience is how to relate system-level learning in higher organisms to synaptic plasticity. Recently, plasticity rules depending not only on pre- and post-synaptic activity but also on a third, non-local neuromodulatory signal have emerged as key candidates to bridge the gap between the macroscopic and the microscopic level of learning. Crucial insights into this topic are expected to be gained from simulations of neural systems, as these allow the simultaneous study of the multiple spatial and temporal scales that are involved in the problem. In particular, synaptic plasticity can be studied during the whole learning process, i.e., on a time scale of minutes to hours and across multiple brain areas. Implementing neuromodulated plasticity in large-scale network simulations where the neuromodulatory signal is dynamically generated by the network itself is challenging, because the network structure is commonly defined purely by the connectivity graph without explicit reference to the embedding of the nodes in physical space. Furthermore, the simulation of networks with realistic connectivity entails the use of distributed computing. A neuromodulated synapse must therefore be informed in an efficient way about the neuromodulatory signal, which is typically generated by a population of neurons located on different machines than either the pre- or post-synaptic neuron. Here, we develop a general framework to solve the problem of implementing neuromodulated plasticity in a time-driven distributed simulation, without reference to a particular implementation language, neuromodulator, or neuromodulated plasticity mechanism. We implement our framework in the simulator NEST and demonstrate excellent scaling up to 1024 processors for simulations of a recurrent network incorporating neuromodulated spike-timing dependent plasticity. PMID:21151370

Metabolic plasticity during mammalian development is directionally dependent on early nutritional status.

PubMed

Gluckman, Peter D; Lillycrop, Karen A; Vickers, Mark H; Pleasants, Anthony B; Phillips, Emma S; Beedle, Alan S; Burdge, Graham C; Hanson, Mark A

2007-07-31

Developmental plasticity in response to environmental cues can take the form of polyphenism, as for the discrete morphs of some insects, or of an apparently continuous spectrum of phenotype, as for most mammalian traits. The metabolic phenotype of adult rats, including the propensity to obesity, hyperinsulinemia, and hyperphagia, shows plasticity in response to prenatal nutrition and to neonatal administration of the adipokine leptin. Here, we report that the effects of neonatal leptin on hepatic gene expression and epigenetic status in adulthood are directionally dependent on the animal's nutritional status in utero. These results demonstrate that, during mammalian development, the direction of the response to one cue can be determined by previous exposure to another, suggesting the potential for a discontinuous distribution of environmentally induced phenotypes, analogous to the phenomenon of polyphenism.

Unravelling the physics of size-dependent dislocation-mediated plasticity

NASA Astrophysics Data System (ADS)

El-Awady, Jaafar A.

2015-01-01

Size-affected dislocation-mediated plasticity is important in a wide range of materials and technologies. Here we develop a generalized size-dependent dislocation-based model that predicts strength as a function of crystal/grain size and the dislocation density. Three-dimensional (3D) discrete dislocation dynamics (DDD) simulations reveal the existence of a well-defined relationship between strength and dislocation microstructure at all length scales for both single crystals and polycrystalline materials. The results predict a transition from dislocation-source strengthening to forest-dominated strengthening at a size-dependent critical dislocation density. It is also shown that the Hall-Petch relationship can be physically interpreted by coupling with an appropriate kinetic equation of the evolution of the dislocation density in polycrystals. The model is shown to be in remarkable agreement with experiments. This work presents a micro-mechanistic framework to predict and interpret strength size-scale effects, and provides an avenue towards performing multiscale simulations without ad hoc assumptions.

Learning Probabilistic Inference through Spike-Timing-Dependent Plasticity123

PubMed Central

Pecevski, Dejan

2016-01-01

Abstract Numerous experimental data show that the brain is able to extract information from complex, uncertain, and often ambiguous experiences. Furthermore, it can use such learnt information for decision making through probabilistic inference. Several models have been proposed that aim at explaining how probabilistic inference could be performed by networks of neurons in the brain. We propose here a model that can also explain how such neural network could acquire the necessary information for that from examples. We show that spike-timing-dependent plasticity in combination with intrinsic plasticity generates in ensembles of pyramidal cells with lateral inhibition a fundamental building block for that: probabilistic associations between neurons that represent through their firing current values of random variables. Furthermore, by combining such adaptive network motifs in a recursive manner the resulting network is enabled to extract statistical information from complex input streams, and to build an internal model for the distribution p* that generates the examples it receives. This holds even if p* contains higher-order moments. The analysis of this learning process is supported by a rigorous theoretical foundation. Furthermore, we show that the network can use the learnt internal model immediately for prediction, decision making, and other types of probabilistic inference. PMID:27419214

Continuous liquid level detection based on two parallel plastic optical fibers in a helical structure

NASA Astrophysics Data System (ADS)

Zhang, Yingzi; Hou, Yulong; Zhang, Yanjun; Hu, Yanjun; Zhang, Liang; Gao, Xiaolong; Zhang, Huixin; Liu, Wenyi

2018-02-01

A simple and low-cost continuous liquid-level sensor based on two parallel plastic optical fibers (POFs) in a helical structure is presented. The change in the liquid level is determined by measuring the side-coupling power in the passive fiber. The side-coupling ratio is increased by just filling the gap between the two POFs with ultraviolet-curable optical cement, making the proposed sensor competitive. The experimental results show that the side-coupling power declines as the liquid level rises. The sensitivity and the measurement range are flexible and affected by the geometric parameters of the helical structure. A higher sensitivity of 0.0208 μW/mm is acquired for a smaller curvature radius of 5 mm, and the measurement range can be expanded to 120 mm by enlarging the screw pitch to 40 mm. In addition, the reversibility and temperature dependence are studied. The proposed sensor is a cost-effective solution offering the advantages of a simple fabrication process, good reversibility, and compensable temperature dependence.

Structural synaptic plasticity in the hippocampus induced by spatial experience and its implications in information processing.

PubMed

Carasatorre, M; Ramírez-Amaya, V; Díaz Cintra, S

2016-10-01

Long-lasting memory formation requires that groups of neurons processing new information develop the ability to reproduce the patterns of neural activity acquired by experience. Changes in synaptic efficiency let neurons organise to form ensembles that repeat certain activity patterns again and again. Among other changes in synaptic plasticity, structural modifications tend to be long-lasting which suggests that they underlie long-term memory. There is a large body of evidence supporting that experience promotes changes in the synaptic structure, particularly in the hippocampus. Structural changes to the hippocampus may be functionally implicated in stabilising acquired memories and encoding new information. Copyright © 2012 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Size-dependent plastic deformation of twinned nanopillars in body-centered cubic tungsten

NASA Astrophysics Data System (ADS)

Xu, Shuozhi; Startt, Jacob K.; Payne, Thomas G.; Deo, Chaitanya S.; McDowell, David L.

2017-05-01

Compared with face-centered cubic metals, twinned nanopillars in body-centered cubic (BCC) systems are much less explored partly due to the more complicated plastic deformation behavior and a lack of reliable interatomic potentials for the latter. In this paper, the fault energies predicted by two semi-empirical interatomic potentials in BCC tungsten (W) are first benchmarked against density functional theory calculations. Then, the more accurate potential is employed in large scale molecular dynamics simulations of tensile and compressive loading of twinned nanopillars in BCC W with different cross sectional shapes and sizes. A single crystal, a twinned crystal, and single crystalline nanopillars are also studied as references. Analyses of the stress-strain response and defect nucleation reveal a strong tension-compression asymmetry and a weak pillar size dependence in the yield strength. Under both tensile and compressive loading, plastic deformation in the twinned nanopillars is dominated by dislocation slip on {110} planes that are nucleated from the intersections between the twin boundary and the pillar surface. It is also found that the cross sectional shape of nanopillars affects the strength and the initial site of defect nucleation but not the overall stress-strain response and plastic deformation behavior.

Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism

PubMed Central

Kraft, Andrew W.; Mitra, Anish; Bauer, Adam Q.; Raichle, Marcus E.; Culver, Joseph P.; Lee, Jin-Moo

2017-01-01

Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism. PMID:29087327

Effects of plastic film residues on occurrence of phthalates and microbial activity in soils.

PubMed

Wang, Jun; Lv, Shenghong; Zhang, Manyun; Chen, Gangcai; Zhu, Tongbin; Zhang, Shen; Teng, Ying; Christie, Peter; Luo, Yongming

2016-05-01

Plastic film mulching has played an important role in Chinese agriculture, especially in vegetable production, but large amounts of film residues can accumulate in the soil. The present study investigated the effects of plastic film residues on the occurrence of soil PAEs and microbial activities using a batch pot experiment. PAE concentrations increased with increasing plastic film residues but the soil microbial carbon and nitrogen, enzyme activities and microbial diversity decreased significantly. At the end of the experiment the PAE concentrations were 0-2.02 mg kg(-1) in the different treatments. Soil microbial C and N, enzyme activities, AWCD value, and Shannon-Weaver and Simpson indices declined by about 28.9-76.2%, 14.9-59.0%, 4.9-22.7%, 23.0-42.0% and 1.8-18.7%, respectively. Soil microbial activity was positively correlated with soil PAE concentration, and soil PAE concentrations were impacted by plastic color and residue volume. Correlations among, and molecular mechanisms of, plastic film residues, PAE occurrence and microbial activity require further study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Humidity-activated shape memory effect on plasticized starch-based biomaterials.

PubMed

Sessini, Valentina; Arrieta, Marina P; Fernández-Torres, Alberto; Peponi, Laura

2018-01-01

Humidity-activated shape memory behavior of plasticized starch-based films reinforced with the innovative combination of starch nanocrystals (SNCs) and catechin as antioxidant were studied. In a previous work, we reported the processing of gelatinized starch-based films filled with SNCs and catechin as antioxidant agent, and we observed that this novel combination leads to starch-based film with enhanced thermal and mechanical performance. In this work, the humidity-activated shape memory behavior of the previous developed starch-based films was characterized. The moisture loss as well as the moisture absorption were studied since they are essential parameters in humidity-activated shape memory polymers to fix the temporary shape and to recover the original shape, respectively. Therefore, the effect of the incorporation of SNCs and catechin on the humidity-activated shape memory properties of plasticized starch was also studied. Moreover, the effectiveness of catechin to increase the polymer stability under oxidative atmosphere and the thermo-mechanical relaxation of all the starch-based materials were studied. The combination of plasticized starch matrix loaded with both, SNCs and catechin, leads to a multifunctional starch-based films with increased hydrophilicity and with excellent humidity-activated shape memory behavior with interest for potential biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural disorder in plant proteins: where plasticity meets sessility.

PubMed

Covarrubias, Alejandra A; Cuevas-Velazquez, Cesar L; Romero-Pérez, Paulette S; Rendón-Luna, David F; Chater, Caspar C C

2017-09-01

Plants are sessile organisms. This intriguing nature provokes the question of how they survive despite the continual perturbations caused by their constantly changing environment. The large amount of knowledge accumulated to date demonstrates the fascinating dynamic and plastic mechanisms, which underpin the diverse strategies selected in plants in response to the fluctuating environment. This phenotypic plasticity requires an efficient integration of external cues to their growth and developmental programs that can only be achieved through the dynamic and interactive coordination of various signaling networks. Given the versatility of intrinsic structural disorder within proteins, this feature appears as one of the leading characters of such complex functional circuits, critical for plant adaptation and survival in their wild habitats. In this review, we present information of those intrinsically disordered proteins (IDPs) from plants for which their high level of predicted structural disorder has been correlated with a particular function, or where there is experimental evidence linking this structural feature with its protein function. Using examples of plant IDPs involved in the control of cell cycle, metabolism, hormonal signaling and regulation of gene expression, development and responses to stress, we demonstrate the critical importance of IDPs throughout the life of the plant.

Respiratory Muscle Plasticity

PubMed Central

Gransee, Heather M.; Mantilla, Carlos B.; Sieck, Gary C.

2014-01-01

Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle’s plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. PMID:23798306

A 2D Material based Gate Tunable Memristive Device for Emulating Modulatory Input-dependent Hetero-synaptic Plasticity.

NASA Astrophysics Data System (ADS)

Yan, Xiaodong; Tian, He; Xie, Yujun; Kostelec, Andrew; Zhao, Huan; Cha, Judy J.; Tice, Jesse; Wang, Han

Modulatory input-dependent plasticity is a well-known type of hetero-synaptic response where the release of neuromodulators can alter the efficacy of neurotransmission in a nearby chemical synapse. Solid-state devices that can mimic such phenomenon are desirable for enhancing the functionality and reconfigurability of neuromorphic electronics. In this work, we demonstrated a tunable artificial synaptic device concept based on the properties of graphene and tin oxide that can mimic the modulatory input-dependent plasticity. By using graphene as the contact electrode, a third electrode terminal can be used to modulate the conductive filament formation in the vertical tin oxide based resistive memory device. The resulting synaptic characteristics of this device, in terms of the profile of synaptic weight change and the spike-timing-dependent-plasticity, is tunable with the bias at the modulating terminal. Furthermore, the synaptic response can be reconfigured between excitatory and inhibitory modes by this modulating bias. The operation mechanism of the device is studied with combined experimental and theoretical analysis. The device is attractive for application in neuromorphic electronics. This work is supported by ARO and NG-ION2 at USC.

Spatiotemporal Computations of an Excitable and Plastic Brain: Neuronal Plasticity Leads to Noise-Robust and Noise-Constructive Computations

PubMed Central

Toutounji, Hazem; Pipa, Gordon

2014-01-01

It is a long-established fact that neuronal plasticity occupies the central role in generating neural function and computation. Nevertheless, no unifying account exists of how neurons in a recurrent cortical network learn to compute on temporally and spatially extended stimuli. However, these stimuli constitute the norm, rather than the exception, of the brain's input. Here, we introduce a geometric theory of learning spatiotemporal computations through neuronal plasticity. To that end, we rigorously formulate the problem of neural representations as a relation in space between stimulus-induced neural activity and the asymptotic dynamics of excitable cortical networks. Backed up by computer simulations and numerical analysis, we show that two canonical and widely spread forms of neuronal plasticity, that is, spike-timing-dependent synaptic plasticity and intrinsic plasticity, are both necessary for creating neural representations, such that these computations become realizable. Interestingly, the effects of these forms of plasticity on the emerging neural code relate to properties necessary for both combating and utilizing noise. The neural dynamics also exhibits features of the most likely stimulus in the network's spontaneous activity. These properties of the spatiotemporal neural code resulting from plasticity, having their grounding in nature, further consolidate the biological relevance of our findings. PMID:24651447

The Stress-Dependent Activation Parameters for Dislocation Nucleation in Molybdenum Nanoparticles.

PubMed

Chachamovitz, Doron; Mordehai, Dan

2018-03-02

Many specimens at the nanoscale are pristine of dislocations, line defects which are the main carriers of plasticity. As a result, they exhibit extremely high strengths which are dislocation-nucleation controlled. Since nucleation is a thermally activated process, it is essential to quantify the stress-dependent activation parameters for dislocation nucleation in order to study the strength of specimens at the nanoscale and its distribution. In this work, we calculate the strength of Mo nanoparticles in molecular dynamics simulations and we propose a method to extract the activation free-energy barrier for dislocation nucleation from the distribution of the results. We show that by deforming the nanoparticles at a constant strain rate, their strength distribution can be approximated by a normal distribution, from which the activation volumes at different stresses and temperatures are calculated directly. We found that the activation energy dependency on the stress near spontaneous nucleation conditions obeys a power-law with a critical exponent of approximately 3/2, which is in accordance with critical exponents found in other thermally activated processes but never for dislocation nucleation. Additionally, significant activation entropies were calculated. Finally, we generalize the approach to calculate the activation parameters for other driving-force dependent thermally activated processes.

Experimental evaluation criteria for constitutive models of time dependent cyclic plasticity

NASA Technical Reports Server (NTRS)

Martin, J. F.

1986-01-01

Notched members were tested at temperatures far above those recorded till now. Simulation of the notch root stress response was accomplished to establish notch stress-strain behavior. Cyclic stress-strain profiles across the net-section were recorded and on-line direct notch strain control was accomplished. Data are compared to three analysis techniques with good results. The objective of the study is to generate experimental data that can be used to evaluate the accuracy of constitutive models of time dependent cyclic plasticity.

Mechanistic and structural basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity

NASA Astrophysics Data System (ADS)

Sahoo, Bikash R.; Maruyama, Kenta; Edula, Jyotheeswara R.; Tougan, Takahiro; Lin, Yuxi; Lee, Young-Ho; Horii, Toshihiro; Fujiwara, Toshimichi

2017-03-01

Peptide-drug discovery using host-defense peptides becomes promising against antibiotic-resistant pathogens and cancer cells. Here, we customized the therapeutic activity of bovine cathelicidin-5 targeting to bacteria, protozoa, and tumor cells. The membrane dependent conformational adaptability and plasticity of cathelicidin-5 is revealed by biophysical analysis and atomistic simulations over 200 μs in thymocytes, leukemia, and E. coli cell-membranes. Our understanding of energy-dependent cathelicidin-5 intrusion in heterogeneous membranes aided in designing novel loss/gain-of-function analogues. In vitro findings identified leucine-zipper to phenylalanine substitution in cathelicidin-5 (1-18) significantly enhance the antimicrobial and anticancer activity with trivial hemolytic activity. Targeted mutants of cathelicidin-5 at kink region and N-terminal truncation revealed loss-of-function. We ensured the existence of a bimodal mechanism of peptide action (membranolytic and non-membranolytic) in vitro. The melanoma mouse model in vivo study further supports the in vitro findings. This is the first structural report on cathelicidin-5 and our findings revealed potent therapeutic application of designed cathelicidin-5 analogues.

Similarities in temperature-dependent gene expression plasticity across timescales in threespine stickleback (Gasterosteus aculeatus).

PubMed

Metzger, David C H; Schulte, Patricia M

2018-04-14

Phenotypic plasticity occurs at a variety of timescales, but little is known about the degree to which plastic responses at different timescales are associated with similar underlying molecular processes, which is critical for assessing the effects of plasticity on evolutionary trajectories. To address this issue, we identified differential gene expression in response to developmental temperature in the muscle transcriptome of adult threespine stickleback (Gasterosteus aculeatus) exposed to 12, 18 and 24°C until hatch and then held at 18°C for 9 months and compared these results to differential gene expression in response to adult thermal acclimation in stickleback developed at 18°C and then acclimated to 5 and 25°C as adults. Adult thermal acclimation affected the expression of 7,940 and 7,015 genes in response to cold and warm acclimation, respectively, and 4,851 of these genes responded in both treatments. In contrast, the expression of only 33 and 29 genes was affected by cold and warm development, respectively. The majority of the genes affected by developmental temperature were also affected by adult acclimation temperature. Many genes that were differentially expressed as a result of adult acclimation were associated with previously identified temperature-dependent effects on DNA methylation patterns, suggesting a role of epigenetic mechanisms in regulating gene expression plasticity during acclimation. Taken together, these results demonstrate similarities between the persistent effects of developmental plasticity on gene expression and the effects of adult thermal acclimation, emphasizing the potential for mechanistic links between plasticity acting at these different life stages. © 2018 John Wiley & Sons Ltd.

Plasticity in the Human Visual Cortex: An Ophthalmology-Based Perspective

PubMed Central

Rosa, Andreia Martins; Silva, Maria Fátima; Murta, Joaquim

2013-01-01

Neuroplasticity refers to the ability of the brain to reorganize the function and structure of its connections in response to changes in the environment. Adult human visual cortex shows several manifestations of plasticity, such as perceptual learning and adaptation, working under the top-down influence of attention. Plasticity results from the interplay of several mechanisms, including the GABAergic system, epigenetic factors, mitochondrial activity, and structural remodeling of synaptic connectivity. There is also a downside of plasticity, that is, maladaptive plasticity, in which there are behavioral losses resulting from plasticity changes in the human brain. Understanding plasticity mechanisms could have major implications in the diagnosis and treatment of ocular diseases, such as retinal disorders, cataract and refractive surgery, amblyopia, and in the evaluation of surgical materials and techniques. Furthermore, eliciting plasticity could open new perspectives in the development of strategies that trigger plasticity for better medical and surgical outcomes. PMID:24205505

Environmental enrichment accelerates ocular dominance plasticity in mouse visual cortex whereas transfer to standard cages resulted in a rapid loss of increased plasticity.

PubMed

Kalogeraki, Evgenia; Pielecka-Fortuna, Justyna; Löwel, Siegrid

2017-01-01

In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in the primary visual cortex (V1) rapidly declines with age: in postnatal day 25-35 (critical period) mice, 4 days of monocular deprivation (MD) are sufficient to induce OD-shifts towards the open eye; thereafter, 7 days of MD are needed. Beyond postnatal day 110, even 14 days of MD failed to induce OD-plasticity in mouse V1. In contrast, mice raised in a so-called "enriched environment" (EE), exhibit lifelong OD-plasticity. EE-mice have more voluntary physical exercise (running wheels), and experience more social interactions (bigger housing groups) and more cognitive stimulation (regularly changed labyrinths or toys). Whether experience-dependent shifts of V1-activation happen faster in EE-mice and how long the plasticity promoting effect would persist after transferring EE-mice back to SCs has not yet been investigated. To this end, we used intrinsic signal optical imaging to visualize V1-activation i) before and after MD in EE-mice of different age groups (from 1-9 months), and ii) after transferring mice back to SCs after postnatal day 130. Already after 2 days of MD, and thus much faster than in SC-mice, EE-mice of all tested age groups displayed a significant OD-shift towards the open eye. Transfer of EE-mice to SCs immediately abolished OD-plasticity: already after 1 week of SC-housing and MD, OD-shifts could no longer be visualized. In an attempt to rescue abolished OD-plasticity of these mice, we either administered the anti-depressant fluoxetine (in drinking water) or supplied a running wheel in the SCs. OD-plasticity was only rescued for the running wheel- mice. Altogether our results show that raising mice in less deprived environments like large EE-cages strongly accelerates experience-dependent changes in V1-activation compared to the impoverished SC-raising. Furthermore, preventing voluntary physical exercise of EE-mice in adulthood immediately precludes OD

Environmental enrichment accelerates ocular dominance plasticity in mouse visual cortex whereas transfer to standard cages resulted in a rapid loss of increased plasticity

PubMed Central

Pielecka-Fortuna, Justyna; Löwel, Siegrid

2017-01-01

In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in the primary visual cortex (V1) rapidly declines with age: in postnatal day 25–35 (critical period) mice, 4 days of monocular deprivation (MD) are sufficient to induce OD-shifts towards the open eye; thereafter, 7 days of MD are needed. Beyond postnatal day 110, even 14 days of MD failed to induce OD-plasticity in mouse V1. In contrast, mice raised in a so-called “enriched environment” (EE), exhibit lifelong OD-plasticity. EE-mice have more voluntary physical exercise (running wheels), and experience more social interactions (bigger housing groups) and more cognitive stimulation (regularly changed labyrinths or toys). Whether experience-dependent shifts of V1-activation happen faster in EE-mice and how long the plasticity promoting effect would persist after transferring EE-mice back to SCs has not yet been investigated. To this end, we used intrinsic signal optical imaging to visualize V1-activation i) before and after MD in EE-mice of different age groups (from 1–9 months), and ii) after transferring mice back to SCs after postnatal day 130. Already after 2 days of MD, and thus much faster than in SC-mice, EE-mice of all tested age groups displayed a significant OD-shift towards the open eye. Transfer of EE-mice to SCs immediately abolished OD-plasticity: already after 1 week of SC-housing and MD, OD-shifts could no longer be visualized. In an attempt to rescue abolished OD-plasticity of these mice, we either administered the anti-depressant fluoxetine (in drinking water) or supplied a running wheel in the SCs. OD-plasticity was only rescued for the running wheel- mice. Altogether our results show that raising mice in less deprived environments like large EE-cages strongly accelerates experience-dependent changes in V1-activation compared to the impoverished SC-raising. Furthermore, preventing voluntary physical exercise of EE-mice in adulthood immediately precludes

Self-Organized Near-Zero-Lag Synchronization Induced by Spike-Timing Dependent Plasticity in Cortical Populations

PubMed Central

Matias, Fernanda S.; Carelli, Pedro V.; Mirasso, Claudio R.; Copelli, Mauro

2015-01-01

Several cognitive tasks related to learning and memory exhibit synchronization of macroscopic cortical areas together with synaptic plasticity at neuronal level. Therefore, there is a growing effort among computational neuroscientists to understand the underlying mechanisms relating synchrony and plasticity in the brain. Here we numerically study the interplay between spike-timing dependent plasticity (STDP) and anticipated synchronization (AS). AS emerges when a dominant flux of information from one area to another is accompanied by a negative time lag (or phase). This means that the receiver region pulses before the sender does. In this paper we study the interplay between different synchronization regimes and STDP at the level of three-neuron microcircuits as well as cortical populations. We show that STDP can promote auto-organized zero-lag synchronization in unidirectionally coupled neuronal populations. We also find synchronization regimes with negative phase difference (AS) that are stable against plasticity. Finally, we show that the interplay between negative phase difference and STDP provides limited synaptic weight distribution without the need of imposing artificial boundaries. PMID:26474165

Dia-Interacting Protein (DIP) Imposes Migratory Plasticity in mDia2-Dependent Tumor Cells in Three-Dimensional Matrices

PubMed Central

Wyse, Meghan M.; Lei, Jun; Nestor-Kalinoski, Andrea L.; Eisenmann, Kathryn M.

2012-01-01

Tumor cells rely upon membrane pliancy to escape primary lesions and invade secondary metastatic sites. This process relies upon localized assembly and disassembly cycles of F-actin that support and underlie the plasma membrane. Dynamic actin generates both spear-like and bleb structures respectively characterizing mesenchymal and amoeboid motility programs utilized by metastatic cells in three-dimensional matrices. The molecular mechanism and physiological trigger(s) driving membrane plasticity are poorly understood. mDia formins are F-actin assembly factors directing membrane pliancy in motile cells. mDia2 is functionally coupled with its binding partner DIP, regulating cortical actin and inducing membrane blebbing in amoeboid cells. Here we show that mDia2 and DIP co-tether to nascent blebs and this linkage is required for bleb formation. DIP controls mesenchymal/amoeboid cell interconvertability, while CXCL12 induces assembly of mDia2:DIP complexes to bleb cortices in 3D matrices. These results demonstrate how DIP-directed mDia2-dependent F-actin dynamics regulate morphological plasticity in motile cancer cells. PMID:23024796

Evolution of a plastic quantitative trait in an age-structured population in a fluctuating environment.

PubMed

Engen, Steinar; Lande, Russell; Saether, Bernt-Erik

2011-10-01

We analyze weak fluctuating selection on a quantitative character in an age-structured population not subject to density regulation. We assume that early in the first year of life before selection, during a critical state of development, environments exert a plastic effect on the phenotype, which remains constant throughout the life of an individual. Age-specific selection on the character affects survival and fecundity, which have intermediate optima subject to temporal environmental fluctuations with directional selection in some age classes as special cases. Weighting individuals by their reproductive value, as suggested by Fisher, we show that the expected response per year in the weighted mean character has the same form as for models with no age structure. Environmental stochasticity generates stochastic fluctuations in the weighted mean character following a first-order autoregressive model with a temporally autocorrelated noise term and stationary variance depending on the amount of phenotypic plasticity. The parameters of the process are simple weighted averages of parameters used to describe age-specific survival and fecundity. The "age-specific selective weights" are related to the stable distribution of reproductive values among age classes. This allows partitioning of the change in the weighted mean character into age-specific components. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Neuron-glia metabolic coupling and plasticity.

PubMed

Magistretti, Pierre J

2006-06-01

The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function that has provided the basis for 2-deoxyglucose-based functional imaging with positron emission tomography (PET). Astrocytes play a central role in neurometabolic coupling, and the basic mechanism involves glutamate-stimulated aerobic glycolysis; the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. An operational model, the 'astrocyte-neuron lactate shuttle', is supported experimentally by a large body of evidence, which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies. In addition, this neuron-glia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity. Thus, distinct subregions of the hippocampus are metabolically active at different time points during spatial learning tasks, suggesting that a type of metabolic plasticity, involving by definition neuron-glia coupling, occurs during learning. In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep-wake cycle, with in particular a marked induction of expression of the gene encoding for protein targeting to glycogen (PTG) following sleep deprivation. These data suggest that glial metabolic plasticity is likely to be concomitant with synaptic plasticity.

Activity-Dependent Human Brain Coding/Noncoding Gene Regulatory Networks

PubMed Central

Lipovich, Leonard; Dachet, Fabien; Cai, Juan; Bagla, Shruti; Balan, Karina; Jia, Hui; Loeb, Jeffrey A.

2012-01-01

While most gene transcription yields RNA transcripts that code for proteins, a sizable proportion of the genome generates RNA transcripts that do not code for proteins, but may have important regulatory functions. The brain-derived neurotrophic factor (BDNF) gene, a key regulator of neuronal activity, is overlapped by a primate-specific, antisense long noncoding RNA (lncRNA) called BDNFOS. We demonstrate reciprocal patterns of BDNF and BDNFOS transcription in highly active regions of human neocortex removed as a treatment for intractable seizures. A genome-wide analysis of activity-dependent coding and noncoding human transcription using a custom lncRNA microarray identified 1288 differentially expressed lncRNAs, of which 26 had expression profiles that matched activity-dependent coding genes and an additional 8 were adjacent to or overlapping with differentially expressed protein-coding genes. The functions of most of these protein-coding partner genes, such as ARC, include long-term potentiation, synaptic activity, and memory. The nuclear lncRNAs NEAT1, MALAT1, and RPPH1, composing an RNAse P-dependent lncRNA-maturation pathway, were also upregulated. As a means to replicate human neuronal activity, repeated depolarization of SY5Y cells resulted in sustained CREB activation and produced an inverse pattern of BDNF-BDNFOS co-expression that was not achieved with a single depolarization. RNAi-mediated knockdown of BDNFOS in human SY5Y cells increased BDNF expression, suggesting that BDNFOS directly downregulates BDNF. Temporal expression patterns of other lncRNA-messenger RNA pairs validated the effect of chronic neuronal activity on the transcriptome and implied various lncRNA regulatory mechanisms. lncRNAs, some of which are unique to primates, thus appear to have potentially important regulatory roles in activity-dependent human brain plasticity. PMID:22960213

Calcium signaling, excitability, and synaptic plasticity defects in a mouse model of Alzheimer's disease.

PubMed

Zhang, Hua; Liu, Jie; Sun, Suya; Pchitskaya, Ekaterina; Popugaeva, Elena; Bezprozvanny, Ilya

2015-01-01

Alzheimer's disease (AD) and aging result in impaired ability to store memories, but the cellular mechanisms responsible for these defects are poorly understood. Presenilin 1 (PS1) mutations are responsible for many early-onset familial AD (FAD) cases. The phenomenon of hippocampal long-term potentiation (LTP) is widely used in studies of memory formation and storage. Recent data revealed long-term LTP maintenance (L-LTP) is impaired in PS1-M146V knock-in (KI) FAD mice. To understand the basis for this phenomenon, in the present study we analyzed structural synaptic plasticity in hippocampal cultures from wild type (WT) and KI mice. We discovered that exposure to picrotoxin induces formation of mushroom spines in both WT and KI cultures, but the maintenance of mushroom spines is impaired in KI neurons. This maintenance defect can be explained by an abnormal firing pattern during the consolidation phase of structural plasticity in KI neurons. Reduced frequency of neuronal firing in KI neurons is caused by enhanced calcium-induced calcium release (CICR), enhanced activity of calcium-activated potassium channels, and increased afterhyperpolarization. As a result, "consolidation" pattern of neuronal activity converted to "depotentiation" pattern of neuronal activity in KI neurons. Consistent with this model, we demonstrated that pharmacological inhibitors of CICR (dantrolene), of calcium-activated potassium channels (apamin), and of calcium-dependent phosphatase calcineurin (FK506) are able to rescue structural plasticity defects in KI neurons. Furthermore, we demonstrate that incubation with dantrolene or apamin also rescued L-LTP defects in KI hippocampal slices, suggesting a role for a similar mechanism. This proposed mechanism may be responsible for memory defects in AD but also for age-related memory decline.

Energy dependent response of plastic scintillation detectors to photon radiation of low to medium energy.

PubMed

Ebenau, Melanie; Radeck, Désirée; Bambynek, Markus; Sommer, Holger; Flühs, Dirk; Spaan, Bernhard; Eichmann, Marion

2016-08-01

Plastic scintillation detectors are promising candidates for the dosimetry of low- to medium-energy photons but quantitative knowledge of their energy response is a prerequisite for their correct use. The purpose of this study was to characterize the energy dependent response of small scintillation detectors (active volume <1 mm(3)) made from the commonly used plastic scintillator BC400. Different detectors made from BC400 were calibrated at a number of radiation qualities ranging from 10 to 280 kV and at a (60)Co beam. All calibrations were performed at the Physikalisch-Technische Bundesanstalt, the National Metrology Institute of Germany. The energy response in terms of air kerma, dose to water, and dose to the scintillator was determined. Conversion factors from air kerma to dose to water and to dose to the scintillator were derived from Monte Carlo simulations. In order to quantitatively describe the energy dependence, a semiempirical model known as unimolecular quenching or Birks' formula was fitted to the data and from this the response to secondary electrons generated within the scintillator material BC400 was derived. The detector energy response in terms of air kerma differs for different scintillator sizes and different detector casings. It is therefore necessary to take attenuation within the scintillator and in the casing into account when deriving the response in terms of dose to water from a calibration in terms of air kerma. The measured energy response in terms of dose to water for BC400 cannot be reproduced by the ratio of mean mass energy-absorption coefficients for polyvinyl toluene to water but shows evidence of quenching. The quenching parameter kB in Birks' formula was determined to be kB = (12.3 ± 0.9) mg MeV(-1) cm(-2). The energy response was quantified relative to the response to (60)Co which is the common radiation quality for the calibration of therapy dosemeters. The observed energy dependence could be well explained with the

Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity.

PubMed

Xu, Xiang; Zhao, Jingyue; Xu, Zhen; Peng, Baozhen; Huang, Qiuhua; Arnold, Eddy; Ding, Jianping

2004-08-06

Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, and regulation of the enzymatic activity of IDHs is crucial for their biological functions. Bacterial IDHs are reversibly regulated by phosphorylation of a strictly conserved serine residue at the active site. Eukaryotic NADP-dependent IDHs (NADP-IDHs) have been shown to have diverse important biological functions; however, their regulatory mechanism remains unclear. Structural studies of human cytosolic NADP-IDH (HcIDH) in complex with NADP and in complex with NADP, isocitrate, and Ca2+ reveal three biologically relevant conformational states of the enzyme that differ substantially in the structure of the active site and in the overall structure. A structural segment at the active site that forms a conserved alpha-helix in all known NADP-IDH structures assumes a loop conformation in the open, inactive form of HcIDH; a partially unraveled alpha-helix in the semi-open, intermediate form; and an alpha-helix in the closed, active form. The side chain of Asp279 of this segment occupies the isocitrate-binding site and forms hydrogen bonds with Ser94 (the equivalent of the phosphorylation site in bacterial IDHs) in the inactive form and chelates the metal ion in the active form. The structural data led us to propose a novel self-regulatory mechanism for HcIDH that mimics the phosphorylation mechanism used by the bacterial homologs, consistent with biochemical and biological data. This mechanism might be applicable to other eukaryotic NADP-IDHs. The results also provide insights into the recognition and specificity of substrate and cofactor by eukaryotic NADP-IDHs.

Intracellular ATP influences synaptic plasticity in area CA1 of rat hippocampus via metabolism to adenosine and activity-dependent activation of adenosine A1 receptors.

PubMed

zur Nedden, Stephanie; Hawley, Simon; Pentland, Naomi; Hardie, D Grahame; Doney, Alexander S; Frenguelli, Bruno G

2011-04-20

The extent to which brain slices reflect the energetic status of the in vivo brain has been a subject of debate. We addressed this issue to investigate the recovery of energetic parameters and adenine nucleotides in rat hippocampal slices and the influence this has on synaptic transmission and plasticity. We show that, although adenine nucleotide levels recover appreciably within 10 min of incubation, it takes 3 h for a full recovery of the energy charge (to ≥ 0.93) and that incubation of brain slices at 34°C results in a significantly higher ATP/AMP ratio and a threefold lower activity of AMP-activated protein kinase compared with slices incubated at room temperature. Supplementation of artificial CSF with d-ribose and adenine (Rib/Ade) increased the total adenine nucleotide pool of brain slices, which, when corrected for the influence of the dead cut edges, closely approached in vivo values. Rib/Ade did not affect basal synaptic transmission or paired-pulse facilitation but did inhibit long-term potentiation (LTP) induced by tetanic or weak theta-burst stimulation. This decrease in LTP was reversed by strong theta-burst stimulation or antagonizing the inhibitory adenosine A(1) receptor suggesting that the elevated tissue ATP levels had resulted in greater activity-dependent adenosine release during LTP induction. This was confirmed by direct measurement of adenosine release with adenosine biosensors. These observations provide new insight into the recovery of adenine nucleotides after slice preparation, the sources of loss of such compounds in brain slices, the means by which to restore them, and the functional consequences of doing so.

Perineuronal net, CSPG receptor and their regulation of neural plasticity.

PubMed

Miao, Qing-Long; Ye, Qian; Zhang, Xiao-Hui

2014-08-25

Perineuronal nets (PNNs) are reticular structures resulting from the aggregation of extracellular matrix (ECM) molecules around the cell body and proximal neurite of specific population of neurons in the central nervous system (CNS). Since the first description of PNNs by Camillo Golgi in 1883, the molecular composition, developmental formation and potential functions of these specialized extracellular matrix structures have only been intensively studied over the last few decades. The main components of PNNs are hyaluronan (HA), chondroitin sulfate proteoglycans (CSPGs) of the lectican family, link proteins and tenascin-R. PNNs appear late in neural development, inversely correlating with the level of neural plasticity. PNNs have long been hypothesized to play a role in stabilizing the extracellular milieu, which secures the characteristic features of enveloped neurons and protects them from the influence of malicious agents. Aberrant PNN signaling can lead to CNS dysfunctions like epilepsy, stroke and Alzheimer's disease. On the other hand, PNNs create a barrier which constrains the neural plasticity and counteracts the regeneration after nerve injury. Digestion of PNNs with chondroitinase ABC accelerates functional recovery from the spinal cord injury and restores activity-dependent mechanisms for modifying neuronal connections in the adult animals, indicating that PNN is an important regulator of neural plasticity. Here, we review recent progress in the studies on the formation of PNNs during early development and the identification of CSPG receptor - an essential molecular component of PNN signaling, along with a discussion on their unique regulatory roles in neural plasticity.

DREAM Controls the On/Off Switch of Specific Activity-Dependent Transcription Pathways

PubMed Central

Mellström, Britt; Sahún, Ignasi; Ruiz-Nuño, Ana; Murtra, Patricia; Gomez-Villafuertes, Rosa; Savignac, Magali; Oliveros, Juan C.; Gonzalez, Paz; Kastanauskaite, Asta; Knafo, Shira; Zhuo, Min; Higuera-Matas, Alejandro; Errington, Michael L.; Maldonado, Rafael; DeFelipe, Javier; Jefferys, John G. R.; Bliss, Tim V. P.; Dierssen, Mara

2014-01-01

Changes in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstream regulatory element antagonist modulator), also known as calsenilin/KChIP-3 (K+ channel interacting protein 3), is a Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory. PMID:24366545

Using In Vitro Electrophysiology to Screen Medications: Accumbal Plasticity as an Engram of Alcohol Dependence.

PubMed

Renteria, R; Jeanes, Z M; Mangieri, R A; Maier, E Y; Kircher, D M; Buske, T R; Morrisett, R A

2016-01-01

The nucleus accumbens (NAc) is a central component of the mesocorticolimbic reward system. Increasing evidence strongly implicates long-term synaptic neuroadaptations in glutamatergic excitatory activity of the NAc shell and/or core medium spiny neurons in response to chronic drug and alcohol exposure. Such neuroadaptations likely play a critical role in the development and expression of drug-seeking behaviors. We have observed unique cell-type-specific bidirectional changes in NAc synaptic plasticity (metaplasticity) following acute and chronic intermittent ethanol exposure. Other investigators have also previously observed similar metaplasticity in the NAc following exposure to psychostimulants, opiates, and amazingly, even following an anhedonia-inducing experience. Considering that the proteome of the postsynaptic density likely contains hundreds of biochemicals, proteins and other components and regulators, we believe that there is a large number of potential molecular sites through which accumbal metaplasticity may be involved in chronic alcohol abuse. Many of our companion laboratories are now engaged in identifying and screening medications targeting candidate genes and its products previously linked to maladaptive alcohol phenotypes. We hypothesize that if manipulation of such target genes and their products change NAc plasticity, then that observation constitutes an important validation step for the development of novel therapeutics to treat alcohol dependence. © 2016 Elsevier Inc. All rights reserved.

Thermal activation parameters of plastic flow reveal deformation mechanisms in the CrMnFeCoNi high-entropy alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laplanche, Guillaume; Bonneville, J.; Varvenne, C.

To reveal the operating mechanisms of plastic deformation in an FCC high-entropy alloy, the activation volumes in CrMnFeCoNi have been measured as a function of plastic strain and temperature between 77 K and 423 K using repeated load relaxation experiments. At the yield stress, σ y, the activation volume varies from ~60 b3 at 77 K to ~360 b 3 at 293 K and scales inversely with yield stress. With increasing plastic strain, the activation volume decreases and the trends follow the Cottrell-Stokes law, according to which the inverse activation volume should increase linearly with σ - σ y (Haasenmore » plot). This is consistent with the notion that hardening due to an increase in the density of forest dislocations is naturally associated with a decrease in the activation volume because the spacing between dislocations decreases. The values and trends in activation volume agree with theoretical predictions that treat the HEA as a high-concentration solid-solution-strengthened alloy. Lastly, these results demonstrate that this HEA deforms by the mechanisms typical of solute strengthening in FCC alloys, and thus indicate that the high compositional/structural complexity does not introduce any new intrinsic deformation mechanisms.« less

Thermal activation parameters of plastic flow reveal deformation mechanisms in the CrMnFeCoNi high-entropy alloy

DOE PAGES

Laplanche, Guillaume; Bonneville, J.; Varvenne, C.; ...

2017-10-06

To reveal the operating mechanisms of plastic deformation in an FCC high-entropy alloy, the activation volumes in CrMnFeCoNi have been measured as a function of plastic strain and temperature between 77 K and 423 K using repeated load relaxation experiments. At the yield stress, σ y, the activation volume varies from ~60 b3 at 77 K to ~360 b 3 at 293 K and scales inversely with yield stress. With increasing plastic strain, the activation volume decreases and the trends follow the Cottrell-Stokes law, according to which the inverse activation volume should increase linearly with σ - σ y (Haasenmore » plot). This is consistent with the notion that hardening due to an increase in the density of forest dislocations is naturally associated with a decrease in the activation volume because the spacing between dislocations decreases. The values and trends in activation volume agree with theoretical predictions that treat the HEA as a high-concentration solid-solution-strengthened alloy. Lastly, these results demonstrate that this HEA deforms by the mechanisms typical of solute strengthening in FCC alloys, and thus indicate that the high compositional/structural complexity does not introduce any new intrinsic deformation mechanisms.« less

Plasticity of orientation preference maps in the visual cortex of adult cats.

PubMed

Godde, Ben; Leonhardt, Ralph; Cords, Sven M; Dinse, Hubert R

2002-04-30

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes.

Sleep Drive Is Encoded by Neural Plastic Changes in a Dedicated Circuit.

PubMed

Liu, Sha; Liu, Qili; Tabuchi, Masashi; Wu, Mark N

2016-06-02

Prolonged wakefulness leads to an increased pressure for sleep, but how this homeostatic drive is generated and subsequently persists is unclear. Here, from a neural circuit screen in Drosophila, we identify a subset of ellipsoid body (EB) neurons whose activation generates sleep drive. Patch-clamp analysis indicates these EB neurons are highly sensitive to sleep loss, switching from spiking to burst-firing modes. Functional imaging and translational profiling experiments reveal that elevated sleep need triggers reversible increases in cytosolic Ca(2+) levels, NMDA receptor expression, and structural markers of synaptic strength, suggesting these EB neurons undergo "sleep-need"-dependent plasticity. Strikingly, the synaptic plasticity of these EB neurons is both necessary and sufficient for generating sleep drive, indicating that sleep pressure is encoded by plastic changes within this circuit. These studies define an integrator circuit for sleep homeostasis and provide a mechanism explaining the generation and persistence of sleep drive. Copyright © 2016 Elsevier Inc. All rights reserved.

Detection of structural changes and mechanical properties of light alloys after severe plastic deformation

NASA Astrophysics Data System (ADS)

Krasnoveikin, V. A.; Kozulin, A. A.; Skripnyak, V. A.

2017-11-01

Severe plastic deformation by equal channel angular pressing has been performed to produce light aluminum and magnesium alloy billets with ultrafine-grained structure. The physical and mechanical properties of the processed alloys are examined by studying their microstructure, measuring microhardness, yield strength, and uniaxial tensile strength. A nondestructive testing technique using three-dimensional X-ray tomography is proposed for detecting internal structural defects and monitoring damage formation in the structure of alloys subjected to severe plastic deformation. The investigation results prove the efficiency of the chosen method and selected mode of producing ultrafine-grained light alloys.

Understanding thermally activated plastic deformation behavior of Zircaloy-4

NASA Astrophysics Data System (ADS)

Kumar, N.; Alomari, A.; Murty, K. L.

2018-06-01

Understanding micromechanics of plastic deformation of existing materials is essential for improving their properties further and/or developing advanced materials for much more severe load bearing applications. The objective of the present work was to understand micromechanics of plastic deformation of Zircaloy-4, a zirconium-based alloy used as fuel cladding and channel (in BWRs) material in nuclear reactors. The Zircaloy-4 in recrystallized (at 973 K for 4 h) condition was subjected to uniaxial tensile testing at a constant cross-head velocity at temperatures in the range 293 K-1073 K and repeated stress relaxation tests at 293 K, 573 K, and 773 K. The minimum in the total elongation was indicative of dynamic strain aging phenomenon in this alloy in the intermediate temperature regime. The yield stress of the alloy was separated into effective and athermal components and the transition from thermally activated dislocation glide to athermal regime took place at around 673 K with the athermal stress estimated to be 115 MPa. The activation volume was found to be in the range of 40 b3 to 160 b3. The activation volume values and the data analyses using the solid-solution models in literature indicated dislocation-solute interaction to be a potential deformation mechanism in thermally activated regime. The activation energy calculated at 573 K was very close to that found for diffusivity of oxygen in α-Zr that was suggestive of dislocations-oxygen interaction during plastic deformation. This type of information may be helpful in alloy design in selecting different elements to control the deformation behavior of the material and impart desired mechanical properties in those materials for specific applications.

Activity-dependent dendritic spine neck changes are correlated with synaptic strength

PubMed Central

Araya, Roberto; Vogels, Tim P.; Yuste, Rafael

2014-01-01

Most excitatory inputs in the mammalian brain are made on dendritic spines, rather than on dendritic shafts. Spines compartmentalize calcium, and this biochemical isolation can underlie input-specific synaptic plasticity, providing a raison d’etre for spines. However, recent results indicate that the spine can experience a membrane potential different from that in the parent dendrite, as though the spine neck electrically isolated the spine. Here we use two-photon calcium imaging of mouse neocortical pyramidal neurons to analyze the correlation between the morphologies of spines activated under minimal synaptic stimulation and the excitatory postsynaptic potentials they generate. We find that excitatory postsynaptic potential amplitudes are inversely correlated with spine neck lengths. Furthermore, a spike timing-dependent plasticity protocol, in which two-photon glutamate uncaging over a spine is paired with postsynaptic spikes, produces rapid shrinkage of the spine neck and concomitant increases in the amplitude of the evoked spine potentials. Using numerical simulations, we explore the parameter regimes for the spine neck resistance and synaptic conductance changes necessary to explain our observations. Our data, directly correlating synaptic and morphological plasticity, imply that long-necked spines have small or negligible somatic voltage contributions, but that, upon synaptic stimulation paired with postsynaptic activity, they can shorten their necks and increase synaptic efficacy, thus changing the input/output gain of pyramidal neurons. PMID:24982196

A review of plastic waste biodegradation.

PubMed

Zheng, Ying; Yanful, Ernest K; Bassi, Amarjeet S

2005-01-01

With more and more plastics being employed in human lives and increasing pressure being placed on capacities available for plastic waste disposal, the need for biodegradable plastics and biodegradation of plastic wastes has assumed increasing importance in the last few years. This review looks at the technological advancement made in the development of more easily biodegradable plastics and the biodegradation of conventional plastics by microorganisms. Additives, such as pro-oxidants and starch, are applied in synthetic materials to modify and make plastics biodegradable. Recent research has shown that thermoplastics derived from polyolefins, traditionally considered resistant to biodegradation in ambient environment, are biodegraded following photo-degradation and chemical degradation. Thermoset plastics, such as aliphatic polyester and polyester polyurethane, are easily attacked by microorganisms directly because of the potential hydrolytic cleavage of ester or urethane bonds in their structures. Some microorganisms have been isolated to utilize polyurethane as a sole source of carbon and nitrogen source. Aliphatic-aromatic copolyesters have active commercial applications because of their good mechanical properties and biodegradability. Reviewing published and ongoing studies on plastic biodegradation, this paper attempts to make conclusions on potentially viable methods to reduce impacts of plastic waste on the environment.

Structural plasticity of the social brain: Differential change after socio-affective and cognitive mental training.

PubMed

Valk, Sofie L; Bernhardt, Boris C; Trautwein, Fynn-Mathis; Böckler, Anne; Kanske, Philipp; Guizard, Nicolas; Collins, D Louis; Singer, Tania

2017-10-01

Although neuroscientific research has revealed experience-dependent brain changes across the life span in sensory, motor, and cognitive domains, plasticity relating to social capacities remains largely unknown. To investigate whether the targeted mental training of different cognitive and social skills can induce specific changes in brain morphology, we collected longitudinal magnetic resonance imaging (MRI) data throughout a 9-month mental training intervention from a large sample of adults between 20 and 55 years of age. By means of various daily mental exercises and weekly instructed group sessions, training protocols specifically addressed three functional domains: (i) mindfulness-based attention and interoception, (ii) socio-affective skills (compassion, dealing with difficult emotions, and prosocial motivation), and (iii) socio-cognitive skills (cognitive perspective-taking on self and others and metacognition). MRI-based cortical thickness analyses, contrasting the different training modules against each other, indicated spatially diverging changes in cortical morphology. Training of present-moment focused attention mostly led to increases in cortical thickness in prefrontal regions, socio-affective training induced plasticity in frontoinsular regions, and socio-cognitive training included change in inferior frontal and lateral temporal cortices. Module-specific structural brain changes correlated with training-induced behavioral improvements in the same individuals in domain-specific measures of attention, compassion, and cognitive perspective-taking, respectively, and overlapped with task-relevant functional networks. Our longitudinal findings indicate structural plasticity in well-known socio-affective and socio-cognitive brain networks in healthy adults based on targeted short daily mental practices. These findings could promote the development of evidence-based mental training interventions in clinical, educational, and corporate settings aimed at

Structural plasticity of the social brain: Differential change after socio-affective and cognitive mental training

PubMed Central

Valk, Sofie L.; Bernhardt, Boris C.; Trautwein, Fynn-Mathis; Böckler, Anne; Kanske, Philipp; Guizard, Nicolas; Collins, D. Louis; Singer, Tania

2017-01-01

Although neuroscientific research has revealed experience-dependent brain changes across the life span in sensory, motor, and cognitive domains, plasticity relating to social capacities remains largely unknown. To investigate whether the targeted mental training of different cognitive and social skills can induce specific changes in brain morphology, we collected longitudinal magnetic resonance imaging (MRI) data throughout a 9-month mental training intervention from a large sample of adults between 20 and 55 years of age. By means of various daily mental exercises and weekly instructed group sessions, training protocols specifically addressed three functional domains: (i) mindfulness-based attention and interoception, (ii) socio-affective skills (compassion, dealing with difficult emotions, and prosocial motivation), and (iii) socio-cognitive skills (cognitive perspective-taking on self and others and metacognition). MRI-based cortical thickness analyses, contrasting the different training modules against each other, indicated spatially diverging changes in cortical morphology. Training of present-moment focused attention mostly led to increases in cortical thickness in prefrontal regions, socio-affective training induced plasticity in frontoinsular regions, and socio-cognitive training included change in inferior frontal and lateral temporal cortices. Module-specific structural brain changes correlated with training-induced behavioral improvements in the same individuals in domain-specific measures of attention, compassion, and cognitive perspective-taking, respectively, and overlapped with task-relevant functional networks. Our longitudinal findings indicate structural plasticity in well-known socio-affective and socio-cognitive brain networks in healthy adults based on targeted short daily mental practices. These findings could promote the development of evidence-based mental training interventions in clinical, educational, and corporate settings aimed at

Spike-timing dependent inhibitory plasticity to learn a selective gating of backpropagating action potentials.

PubMed

Wilmes, Katharina Anna; Schleimer, Jan-Hendrik; Schreiber, Susanne

2017-04-01

Inhibition is known to influence the forward-directed flow of information within neurons. However, also regulation of backward-directed signals, such as backpropagating action potentials (bAPs), can enrich the functional repertoire of local circuits. Inhibitory control of bAP spread, for example, can provide a switch for the plasticity of excitatory synapses. Although such a mechanism is possible, it requires a precise timing of inhibition to annihilate bAPs without impairment of forward-directed excitatory information flow. Here, we propose a specific learning rule for inhibitory synapses to automatically generate the correct timing to gate bAPs in pyramidal cells when embedded in a local circuit of feedforward inhibition. Based on computational modeling of multi-compartmental neurons with physiological properties, we demonstrate that a learning rule with anti-Hebbian shape can establish the required temporal precision. In contrast to classical spike-timing dependent plasticity of excitatory synapses, the proposed inhibitory learning mechanism does not necessarily require the definition of an upper bound of synaptic weights because of its tendency to self-terminate once annihilation of bAPs has been reached. Our study provides a functional context in which one of the many time-dependent learning rules that have been observed experimentally - specifically, a learning rule with anti-Hebbian shape - is assigned a relevant role for inhibitory synapses. Moreover, the described mechanism is compatible with an upregulation of excitatory plasticity by disinhibition. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Climate change and temperature-dependent sex determination: can individual plasticity in nesting phenology prevent extreme sex ratios?

PubMed

Schwanz, Lisa E; Janzen, Fredric J

2008-01-01

Under temperature-dependent sex determination (TSD), temperatures experienced by embryos during development determine the sex of the offspring. Consequently, populations of organisms with TSD have the potential to be strongly impacted by climatic warming that could bias offspring sex ratio, a fundamental demographic parameter involved in population dynamics. Moreover, many taxa with TSD are imperiled, so research on this phenomenon, particularly long-term field study, has assumed great urgency. Recently, turtles with TSD have joined the diverse list of taxa that have demonstrated population-level changes in breeding phenology in response to recent climate change. This raises the possibility that any adverse impacts of climate change on populations may be alleviated by individual plasticity in nesting phenology. Here, we examine data from a long-term study on a population of painted turtles (Chrysemys picta) to determine whether changes in phenology are due to individual plasticity and whether individual plasticity in the timing of nesting has the capacity to offset the sex ratio effects of a rise in climatic temperature. We find that individual females show plasticity in the date of first nesting each year, and that this plasticity depends on the climate from the previous winter. First nesting date is not repeatable within individuals, suggesting that it would not respond to selection. Sex ratios of hatchlings within a nest declined nonsignificantly over the nesting season. However, small increases in summer temperature had a much stronger effect on nest sex ratios than did laying nests earlier in the season. For this and other reasons, it seems unlikely that individual plasticity in the timing of nesting will offset the effects of climate change on sex ratios in this population, and we hypothesize that this conclusion applies to other populations with TSD.

Long-Term Plasticity of Neurotransmitter Release: Emerging Mechanisms and Contributions to Brain Function and Disease.

PubMed

Monday, Hannah R; Younts, Thomas J; Castillo, Pablo E

2018-04-25

Long-lasting changes of brain function in response to experience rely on diverse forms of activity-dependent synaptic plasticity. Chief among them are long-term potentiation and long-term depression of neurotransmitter release, which are widely expressed by excitatory and inhibitory synapses throughout the central nervous system and can dynamically regulate information flow in neural circuits. This review article explores recent advances in presynaptic long-term plasticity mechanisms and contributions to circuit function. Growing evidence indicates that presynaptic plasticity may involve structural changes, presynaptic protein synthesis, and transsynaptic signaling. Presynaptic long-term plasticity can alter the short-term dynamics of neurotransmitter release, thereby contributing to circuit computations such as novelty detection, modifications of the excitatory/inhibitory balance, and sensory adaptation. In addition, presynaptic long-term plasticity underlies forms of learning and its dysregulation participates in several neuropsychiatric conditions, including schizophrenia, autism, intellectual disabilities, neurodegenerative diseases, and drug abuse. Expected final online publication date for the Annual Review of Neuroscience Volume 41 is July 8, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mdm2 mediates FMRP- and Gp1 mGluR-dependent protein translation and neural network activity.

PubMed

Liu, Dai-Chi; Seimetz, Joseph; Lee, Kwan Young; Kalsotra, Auinash; Chung, Hee Jung; Lu, Hua; Tsai, Nien-Pei

2017-10-15

Activating Group 1 (Gp1) metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, elicits translation-dependent neural plasticity mechanisms that are crucial to animal behavior and circuit development. Dysregulated Gp1 mGluR signaling has been observed in numerous neurological and psychiatric disorders. However, the molecular pathways underlying Gp1 mGluR-dependent plasticity mechanisms are complex and have been elusive. In this study, we identified a novel mechanism through which Gp1 mGluR mediates protein translation and neural plasticity. Using a multi-electrode array (MEA) recording system, we showed that activating Gp1 mGluR elevates neural network activity, as demonstrated by increased spontaneous spike frequency and burst activity. Importantly, we validated that elevating neural network activity requires protein translation and is dependent on fragile X mental retardation protein (FMRP), the protein that is deficient in the most common inherited form of mental retardation and autism, fragile X syndrome (FXS). In an effort to determine the mechanism by which FMRP mediates protein translation and neural network activity, we demonstrated that a ubiquitin E3 ligase, murine double minute-2 (Mdm2), is required for Gp1 mGluR-induced translation and neural network activity. Our data showed that Mdm2 acts as a translation suppressor, and FMRP is required for its ubiquitination and down-regulation upon Gp1 mGluR activation. These data revealed a novel mechanism by which Gp1 mGluR and FMRP mediate protein translation and neural network activity, potentially through de-repressing Mdm2. Our results also introduce an alternative way for understanding altered protein translation and brain circuit excitability associated with Gp1 mGluR in neurological diseases such as FXS. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nontargeted multicomponent analytical screening of plastic food contact materials using fast interpretation of deliverables via expert structure-activity relationship software.

PubMed

Rothenbacher, Thorsten; Schwack, Wolfgang

2009-01-01

Plastic packaging materials may release compounds into packed foodstuffs. To identify potential migrants of toxicological concern, resins, and multilayer foils (mainly polyethylene) intended for the production of food contact materials were extracted and analyzed by GC/mass spectrometry. To identify even compounds of low concentrations, AMDIS software was used and data evaluation was safeguarded by the Kovats retention index (RI) system. In this way, 46 compounds were identified as possible migrants. The expert structure-activity relationship software DEREK for Windows was utilized to evaluate all identified substances in terms of carcinogenicity, genotoxicity, thyroid toxicity, and miscellaneous endpoints for humans. Additionally, a literature search for these compounds was performed with Sci-Finder, but relevant data were missing for 28 substances. Seven compounds with adverse toxicological effects were identified. In addition, the RIs of 24 commercial additive standards, measured with a GC capillary column of intermediate polarity, are given.

Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices.

PubMed

Zheng, Jing-Jing; Li, Shu-Jing; Zhang, Xiao-Di; Miao, Wan-Ying; Zhang, Dinghong; Yao, Haishan; Yu, Xiang

2014-03-01

Sensory experience is critical to development and plasticity of neural circuits. Here we report a new form of plasticity in neonatal mice, where early sensory experience cross-modally regulates development of all sensory cortices via oxytocin signaling. Unimodal sensory deprivation from birth through whisker deprivation or dark rearing reduced excitatory synaptic transmission in the correspondent sensory cortex and cross-modally in other sensory cortices. Sensory experience regulated synthesis and secretion of the neuropeptide oxytocin as well as its level in the cortex. Both in vivo oxytocin injection and increased sensory experience elevated excitatory synaptic transmission in multiple sensory cortices and significantly rescued the effects of sensory deprivation. Together, these results identify a new function for oxytocin in promoting cross-modal, experience-dependent cortical development. This link between sensory experience and oxytocin is particularly relevant to autism, where hypersensitivity or hyposensitivity to sensory inputs is prevalent and oxytocin is a hotly debated potential therapy.

Atomistic basis for the plastic yield criterion of metallic glass.

PubMed

Schuh, Christopher A; Lund, Alan C

2003-07-01

Because of their disordered atomic structure, amorphous metals (termed metallic glasses) have fundamentally different deformation mechanisms compared with polycrystalline metals. These different mechanisms give metallic glasses high strength, but the extent to which they affect other macroscopic deformation properties is uncertain. For example, the nature of the plastic-yield criterion is a point of contention, with some studies reporting yield behaviour roughly in line with that of polycrystalline metals, and others indicating strong fundamental differences. In particular, it is unclear whether pressure- or normal stress-dependence needs to be included in the plastic-yield criterion of metallic glasses, and how such a dependence could arise from their disordered structure. In this work we provide an atomic-level explanation for pressure-dependent yield in amorphous metals, based on an elementary unit of deformation. This simple model compares favourably with new atomistic simulations of metallic glasses, as well as existing experimental data.

Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

NASA Astrophysics Data System (ADS)

Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takuya; Kim, Yoshiharu

2013-07-01

Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freud's ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity

PubMed Central

Mueller, Karsten; Möller, Harald E.; Horstmann, Annette; Busse, Franziska; Lepsien, Jöran; Blüher, Matthias; Stumvoll, Michael; Villringer, Arno; Pleger, Burkhard

2015-01-01

Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM) and white matter (WM) that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging (MRI) together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training twice a week over a period of 3 months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI), reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C), and alterations of serum brain-derived neurotrophic factor (BDNF) concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing. PMID:26190989

Structure and transport properties of a plastic crystal ion conductor: diethyl(methyl)(isobutyl)phosphonium hexafluorophosphate.

PubMed

Jin, Liyu; Nairn, Kate M; Forsyth, Craig M; Seeber, Aaron J; MacFarlane, Douglas R; Howlett, Patrick C; Forsyth, Maria; Pringle, Jennifer M

2012-06-13

Understanding the ion transport behavior of organic ionic plastic crystals (OIPCs) is crucial for their potential application as solid electrolytes in various electrochemical devices such as lithium batteries. In the present work, the ion transport mechanism is elucidated by analyzing experimental data (single-crystal XRD, multinuclear solid-state NMR, DSC, ionic conductivity, and SEM) as well as the theoretical simulations (second moment-based solid static NMR line width simulations) for the OIPC diethyl(methyl)(isobutyl)phosphonium hexafluorophosphate ([P(1,2,2,4)][PF(6)]). This material displays rich phase behavior and advantageous ionic conductivities, with three solid-solid phase transitions and a highly "plastic" and conductive final solid phase in which the conductivity reaches 10(-3) S cm(-1). The crystal structure shows unique channel-like packing of the cations, which may allow the anions to diffuse more easily than the cations at lower temperatures. The strongly phase-dependent static NMR line widths of the (1)H, (19)F, and (31)P nuclei in this material have been well simulated by different levels of molecular motions in different phases. Thus, drawing together of the analytical and computational techniques has allowed the construction of a transport mechanism for [P(1,2,2,4)][PF(6)]. It is also anticipated that utilization of these techniques will allow a more detailed understanding of the transport mechanisms of other plastic crystal electrolyte materials.

The Role of Neuromodulators in Cortical Plasticity. A Computational Perspective

PubMed Central

Pedrosa, Victor; Clopath, Claudia

2017-01-01

Neuromodulators play a ubiquitous role across the brain in regulating plasticity. With recent advances in experimental techniques, it is possible to study the effects of diverse neuromodulatory states in specific brain regions. Neuromodulators are thought to impact plasticity predominantly through two mechanisms: the gating of plasticity and the upregulation of neuronal activity. However, the consequences of these mechanisms are poorly understood and there is a need for both experimental and theoretical exploration. Here we illustrate how neuromodulatory state affects cortical plasticity through these two mechanisms. First, we explore the ability of neuromodulators to gate plasticity by reshaping the learning window for spike-timing-dependent plasticity. Using a simple computational model, we implement four different learning rules and demonstrate their effects on receptive field plasticity. We then compare the neuromodulatory effects of upregulating learning rate versus the effects of upregulating neuronal activity. We find that these seemingly similar mechanisms do not yield the same outcome: upregulating neuronal activity can lead to either a broadening or a sharpening of receptive field tuning, whereas upregulating learning rate only intensifies the sharpening of receptive field tuning. This simple model demonstrates the need for further exploration of the rich landscape of neuromodulator-mediated plasticity. Future experiments, coupled with biologically detailed computational models, will elucidate the diversity of mechanisms by which neuromodulatory state regulates cortical plasticity. PMID:28119596

Effect of Severe Plastic Deformation on Structure and Properties of Al-Sc-Ta and Al-Sc-Ti Alloys.

PubMed

Berezina, Alla; Monastyrska, Tetiana; Davydenko, Olexandr; Molebny, Oleh; Polishchuk, Sergey

2017-12-01

The comparative analysis of the effect of monotonous and non-monotonous severe plastic deformations (SPD) on the structure and properties of aluminum alloys has been carried out. Conventional hydrostatic extrusion (HE) with a constant deformation direction and equal-channel angular hydroextrusion (ECAH) with an abrupt change in the deformation direction were chosen for the cases of monotonous and non-monotonous SPD, respectively. Model cast hypoeutectic Al-0.3%Sc alloys and hypereutectic Al-0.6%Sc alloys with Ta and Ti additives were chosen for studying. It was demonstrated that SPD of the alloys resulted in the segregation of the material into active and inactive zones which formed a banded structure. The active zones were shown to be bands of localized plastic deformation. The distance between zones was found to be independent of the accumulated strain degree and was in the range of 0.6-1 μm. Dynamic recrystallization in the active zones was observed using TEM. The dynamic recrystallization was accompanied by the formation of disclinations, deformation bands, low-angle, and high-angle boundaries, i.e., rotational deformation modes developed. The dynamic recrystallization was more intense during the non-monotonous deformation as compared with the monotonous one, which was confirmed by the reduction of texture degree in the materials after ECAH.

Effect of Severe Plastic Deformation on Structure and Properties of Al-Sc-Ta and Al-Sc-Ti Alloys

NASA Astrophysics Data System (ADS)

Berezina, Alla; Monastyrska, Tetiana; Davydenko, Olexandr; Molebny, Oleh; Polishchuk, Sergey

2017-03-01

The comparative analysis of the effect of monotonous and non-monotonous severe plastic deformations (SPD) on the structure and properties of aluminum alloys has been carried out. Conventional hydrostatic extrusion (HE) with a constant deformation direction and equal-channel angular hydroextrusion (ECAH) with an abrupt change in the deformation direction were chosen for the cases of monotonous and non-monotonous SPD, respectively. Model cast hypoeutectic Al-0.3%Sc alloys and hypereutectic Al-0.6%Sc alloys with Ta and Ti additives were chosen for studying. It was demonstrated that SPD of the alloys resulted in the segregation of the material into active and inactive zones which formed a banded structure. The active zones were shown to be bands of localized plastic deformation. The distance between zones was found to be independent of the accumulated strain degree and was in the range of 0.6-1 μm. Dynamic recrystallization in the active zones was observed using TEM. The dynamic recrystallization was accompanied by the formation of disclinations, deformation bands, low-angle, and high-angle boundaries, i.e., rotational deformation modes developed. The dynamic recrystallization was more intense during the non-monotonous deformation as compared with the monotonous one, which was confirmed by the reduction of texture degree in the materials after ECAH.

Activity-dependent regulation of NMDAR1 immunoreactivity in the developing visual cortex.

PubMed

Catalano, S M; Chang, C K; Shatz, C J

1997-11-01

NMDA receptors have been implicated in activity-dependent synaptic plasticity in the developing visual cortex. We examined the distribution of immunocytochemically detectable NMDAR1 in visual cortex of cats and ferrets from late embryonic ages to adulthood. Cortical neurons are initially highly immunostained. This level declines gradually over development, with the notable exception of cortical layers 2/3, where levels of NMDAR1 immunostaining remain high into adulthood. Within layer 4, the decline in NMDAR1 immunostaining to adult levels coincides with the completion of ocular dominance column formation and the end of the critical period for layer 4. To determine whether NMDAR1 immunoreactivity is regulated by retinal activity, animals were dark-reared or retinal activity was completely blocked in one eye with tetrodotoxin (TTX). Dark-rearing does not cause detectable changes in NMDAR1 immunoreactivity. However, 2 weeks of monocular TTX administration decreases NMDAR1 immunoreactivity in layer 4 of the columns of the blocked eye. Thus, high levels of NMDAR1 immunostaining within the visual cortex are temporally correlated with ocular dominance column formation and developmental plasticity; the persistence of staining in layers 2/3 also correlates with the physiological plasticity present in these layers in the adult. In addition, visual experience is not required for the developmental changes in the laminar pattern of NMDAR1 levels, but the presence of high levels of NMDAR1 in layer 4 during the critical period does require retinal activity. These observations are consistent with a central role for NMDA receptors in promoting and ultimately limiting synaptic rearrangements in the developing neocortex.

Synaptic plasticity and neuronal refractory time cause scaling behaviour of neuronal avalanches

NASA Astrophysics Data System (ADS)

Michiels van Kessenich, L.; de Arcangelis, L.; Herrmann, H. J.

2016-08-01

Neuronal avalanches measured in vitro and in vivo in different cortical networks consistently exhibit power law behaviour for the size and duration distributions with exponents typical for a mean field self-organized branching process. These exponents are also recovered in neuronal network simulations implementing various neuronal dynamics on different network topologies. They can therefore be considered a very robust feature of spontaneous neuronal activity. Interestingly, this scaling behaviour is also observed on regular lattices in finite dimensions, which raises the question about the origin of the mean field behavior observed experimentally. In this study we provide an answer to this open question by investigating the effect of activity dependent plasticity in combination with the neuronal refractory time in a neuronal network. Results show that the refractory time hinders backward avalanches forcing a directed propagation. Hebbian plastic adaptation plays the role of sculpting these directed avalanche patterns into the topology of the network slowly changing it into a branched structure where loops are marginal.

Synaptic plasticity and neuronal refractory time cause scaling behaviour of neuronal avalanches.

PubMed

Michiels van Kessenich, L; de Arcangelis, L; Herrmann, H J

2016-08-18

Neuronal avalanches measured in vitro and in vivo in different cortical networks consistently exhibit power law behaviour for the size and duration distributions with exponents typical for a mean field self-organized branching process. These exponents are also recovered in neuronal network simulations implementing various neuronal dynamics on different network topologies. They can therefore be considered a very robust feature of spontaneous neuronal activity. Interestingly, this scaling behaviour is also observed on regular lattices in finite dimensions, which raises the question about the origin of the mean field behavior observed experimentally. In this study we provide an answer to this open question by investigating the effect of activity dependent plasticity in combination with the neuronal refractory time in a neuronal network. Results show that the refractory time hinders backward avalanches forcing a directed propagation. Hebbian plastic adaptation plays the role of sculpting these directed avalanche patterns into the topology of the network slowly changing it into a branched structure where loops are marginal.

Acetylcholine-modulated plasticity in reward-driven navigation: a computational study.

PubMed

Zannone, Sara; Brzosko, Zuzanna; Paulsen, Ole; Clopath, Claudia

2018-06-21

Neuromodulation plays a fundamental role in the acquisition of new behaviours. In previous experimental work, we showed that acetylcholine biases hippocampal synaptic plasticity towards depression, and the subsequent application of dopamine can retroactively convert depression into potentiation. We also demonstrated that incorporating this sequentially neuromodulated Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation yields effective learning of changing reward locations. Here, we employ computational modelling to further characterize the effects of cholinergic depression on behaviour. We find that acetylcholine, by allowing learning from negative outcomes, enhances exploration over the action space. We show that this results in a variety of effects, depending on the structure of the model, the environment and the task. Interestingly, sequentially neuromodulated STDP also yields flexible learning, surpassing the performance of other reward-modulated plasticity rules.

Using the virtual brain to reveal the role of oscillations and plasticity in shaping brain's dynamical landscape.

PubMed

Roy, Dipanjan; Sigala, Rodrigo; Breakspear, Michael; McIntosh, Anthony Randal; Jirsa, Viktor K; Deco, Gustavo; Ritter, Petra

2014-12-01

Spontaneous brain activity, that is, activity in the absence of controlled stimulus input or an explicit active task, is topologically organized in multiple functional networks (FNs) maintaining a high degree of coherence. These "resting state networks" are constrained by the underlying anatomical connectivity between brain areas. They are also influenced by the history of task-related activation. The precise rules that link plastic changes and ongoing dynamics of resting-state functional connectivity (rs-FC) remain unclear. Using the framework of the open source neuroinformatics platform "The Virtual Brain," we identify potential computational mechanisms that alter the dynamical landscape, leading to reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that network activity in the absence of plasticity is characterized by irregular oscillations between low-amplitude asynchronous states and high-amplitude synchronous states. We then demonstrate the capability of spike-timing-dependent plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to efficiently influence learning. Further, we show how alpha-state-dependent STDP alters the local area dynamics from an irregular to a highly periodic alpha-like state. This is an important finding, as the cortical input from the thalamus is at the rate of alpha. We demonstrate how resulting rhythmic cortical output in this frequency range acts as a neuronal tuner and, hence, leads to synchronization or de-synchronization between brain areas. Finally, we demonstrate that locally restricted structural connectivity changes influence local as well as global dynamics and lead to altered rs-FC.

Singing activity-driven Arc expression associated with vocal acoustic plasticity in juvenile songbird.

PubMed

Hayase, Shin; Wada, Kazuhiro

2018-06-23

Learned vocalization, including birdsong and human speech, is acquired through self-motivated vocal practice during the sensitive period of vocal learning. The zebra finch (Taeniopygia guttata) develops a song characterized by vocal variability and crystalizes a defined song pattern as adulthood. However, it remains unknown how vocal variability is regulated with diurnal singing during the sensorimotor learning period. Here, we investigated the expression of activity-dependent neuroplasticity-related gene Arc during the early plastic song phase to examine its potential association with vocal plasticity. We first confirmed that multiple acoustic features of syllables in the plastic song were dramatically and simultaneously modulated during the first 3 hours of singing in a day and the altered features were maintained until sleep. Concurrently, Arc was intensely induced during morning singing and a subsequent attenuation during afternoon singing in the robust nucleus of the arcopallium (RA) and the interfacial nucleus of the nidopallium (NIf). The singing-driven Arc expression was not altered by circadian rhythm, but rather reduced during the day as juveniles produced more songs. Song stabilization accelerated by testosterone administration in juveniles was accompanied with attenuation of Arc induction in RA and NIf. In contrast, although early-deafened birds produced highly unstable song even at adulthood, singing-driven Arc expression was not different between intact and early-deafened adults. These results suggest a potential functional link between Arc expression in RA and NIf and vocal plasticity during the sensorimotor phase of song learning. Nonetheless, Arc expression did not reflect the quality of bird's own song or auditory feedback. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Development and Activity-Dependent Expression of Aggrecan in the Cat Visual Cortex

PubMed Central

Sengpiel, F.; Beaver, C. J.; Crocker-Buque, A.; Kelly, G. M.; Matthews, R. T.; Mitchell, D. E.

2013-01-01

The Cat-301 monoclonal antibody identifies aggrecan, a chondroitin sulfate proteoglycan in the cat visual cortex and dorsal lateral geniculate nucleus (dLGN). During development, aggrecan expression increases in the dLGN with a time course that matches the decline in plasticity. Moreover, examination of tissue from selectively visually deprived cats shows that expression is activity dependent, suggesting a role for aggrecan in the termination of the sensitive period. Here, we demonstrate for the first time that the onset of aggrecan expression in area 17 also correlates with the decline in experience-dependent plasticity in visual cortex and that this expression is experience dependent. Dark rearing until 15 weeks of age dramatically reduced the density of aggrecan-positive neurons in the extragranular layers, but not in layer IV. This effect was reversible as dark-reared animals that were subsequently exposed to light showed normal numbers of Cat-301-positive cells. The reduction in aggrecan following certain early deprivation regimens is the first biochemical correlate of the functional changes to the γ-aminobutyric acidergic system that have been reported following early deprivation in cats. PMID:22368089

Transmission, Development, and Plasticity of Synapses

PubMed Central

Harris, Kathryn P.

2015-01-01

Chemical synapses are sites of contact and information transfer between a neuron and its partner cell. Each synapse is a specialized junction, where the presynaptic cell assembles machinery for the release of neurotransmitter, and the postsynaptic cell assembles components to receive and integrate this signal. Synapses also exhibit plasticity, during which synaptic function and/or structure are modified in response to activity. With a robust panel of genetic, imaging, and electrophysiology approaches, and strong evolutionary conservation of molecular components, Drosophila has emerged as an essential model system for investigating the mechanisms underlying synaptic assembly, function, and plasticity. We will discuss techniques for studying synapses in Drosophila, with a focus on the larval neuromuscular junction (NMJ), a well-established model glutamatergic synapse. Vesicle fusion, which underlies synaptic release of neurotransmitters, has been well characterized at this synapse. In addition, studies of synaptic assembly and organization of active zones and postsynaptic densities have revealed pathways that coordinate those events across the synaptic cleft. We will also review modes of synaptic growth and plasticity at the fly NMJ, and discuss how pre- and postsynaptic cells communicate to regulate plasticity in response to activity. PMID:26447126

Learning and retrieval behavior in recurrent neural networks with pre-synaptic dependent homeostatic plasticity

NASA Astrophysics Data System (ADS)

Mizusaki, Beatriz E. P.; Agnes, Everton J.; Erichsen, Rubem; Brunnet, Leonardo G.

2017-08-01

The plastic character of brain synapses is considered to be one of the foundations for the formation of memories. There are numerous kinds of such phenomenon currently described in the literature, but their role in the development of information pathways in neural networks with recurrent architectures is still not completely clear. In this paper we study the role of an activity-based process, called pre-synaptic dependent homeostatic scaling, in the organization of networks that yield precise-timed spiking patterns. It encodes spatio-temporal information in the synaptic weights as it associates a learned input with a specific response. We introduce a correlation measure to evaluate the precision of the spiking patterns and explore the effects of different inhibitory interactions and learning parameters. We find that large learning periods are important in order to improve the network learning capacity and discuss this ability in the presence of distinct inhibitory currents.

On a phase diagram for random neural networks with embedded spike timing dependent plasticity.

PubMed

Turova, Tatyana S; Villa, Alessandro E P

2007-01-01

This paper presents an original mathematical framework based on graph theory which is a first attempt to investigate the dynamics of a model of neural networks with embedded spike timing dependent plasticity. The neurons correspond to integrate-and-fire units located at the vertices of a finite subset of 2D lattice. There are two types of vertices, corresponding to the inhibitory and the excitatory neurons. The edges are directed and labelled by the discrete values of the synaptic strength. We assume that there is an initial firing pattern corresponding to a subset of units that generate a spike. The number of activated externally vertices is a small fraction of the entire network. The model presented here describes how such pattern propagates throughout the network as a random walk on graph. Several results are compared with computational simulations and new data are presented for identifying critical parameters of the model.

Structure of polyhydroxyalkanoate (PHA) synthase PhaC from Chromobacterium sp. USM2, producing biodegradable plastics.

PubMed

Chek, Min Fey; Kim, Sun-Yong; Mori, Tomoyuki; Arsad, Hasni; Samian, Mohammed Razip; Sudesh, Kumar; Hakoshima, Toshio

2017-07-13

Polyhydroxyalkanoate (PHA) is a promising candidate for use as an alternative bioplastic to replace petroleum-based plastics. Our understanding of PHA synthase PhaC is poor due to the paucity of available three-dimensional structural information. Here we present a high-resolution crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, PhaC Cs -CAT. The structure shows that PhaC Cs -CAT forms an α/β hydrolase fold comprising α/β core and CAP subdomains. The active site containing Cys291, Asp447 and His477 is located at the bottom of the cavity, which is filled with water molecules and is covered by the partly disordered CAP subdomain. We designated our structure as the closed form, which is distinct from the recently reported catalytic domain from Cupriavidus necator (PhaC Cn -CAT). Structural comparison showed PhaC Cn -CAT adopting a partially open form maintaining a narrow substrate access channel to the active site, but no product egress. PhaC Cs -CAT forms a face-to-face dimer mediated by the CAP subdomains. This arrangement of the dimer is also distinct from that of the PhaC Cn -CAT dimer. These findings suggest that the CAP subdomain should undergo a conformational change during catalytic activity that involves rearrangement of the dimer to facilitate substrate entry and product formation and egress from the active site.

Neuronal activity-dependent membrane traffic at the neuromuscular junction

PubMed Central

Miana-Mena, Francisco Javier; Roux, Sylvie; Benichou, Jean-Claude; Osta, Rosario; Brûlet, Philippe

2002-01-01

During development and also in adulthood, synaptic connections are modulated by neuronal activity. To follow such modifications in vivo, new genetic tools are designed. The nontoxic C-terminal fragment of tetanus toxin (TTC) fused to a reporter gene such as LacZ retains the retrograde and transsynaptic transport abilities of the holotoxin itself. In this work, the hybrid protein is injected intramuscularly to analyze in vivo the mechanisms of intracellular and transneuronal traffics at the neuromuscular junction (NMJ). Traffic on both sides of the synapse are strongly dependent on presynaptic neural cell activity. In muscle, a directional membrane traffic concentrates β-galactosidase-TTC hybrid protein into the NMJ postsynaptic side. In neurons, the probe is sorted across the cell to dendrites and subsequently to an interconnected neuron. Such fusion protein, sensitive to presynaptic neuronal activity, would be extremely useful to analyze morphological changes and plasticity at the NMJ. PMID:11880654

Neuronal plasticity depending on a glycoprotein synthesized in goldfish leptomeninx.

PubMed

Schmidt, R; Rother, S; Schlingensiepen, K H; Brysch, W

1992-01-01

Transcription of a calcium and zinc binding, nervous system-specific cell adhesion glycoprotein, ependymin, in goldfish leptomeninx was significantly enhanced after active avoidance conditioning, followed by enhanced translation and secretion. Inactivation of secreted ependymin by injected antisera interfered with behavioral adaptations. In addition to the site of synthesis in reticular cells of the leptomeninx electronmicroscopic immunochemistry localized the protein to tectal neurons of the superficial plexiform and the periventricular cell layers. Detection of ependymin in cells where it is not synthesized, namely in neurons, suggests a re-uptake during functional activity of the CNS and assigns a pivotal role to the cerebrospinal and interstitial brain fluids for the distribution of protein factors that support axonal growth and neuronal plasticity.

Low-grade inflammation disrupts structural plasticity in the human brain.

PubMed

Szabó, C; Kelemen, O; Kéri, S

2014-09-05

Increased low-grade inflammation is thought to be associated with several neuropsychiatric disorders characterized by decreased neuronal plasticity. The purpose of the present study was to investigate the relationship between structural changes in the human brain during cognitive training and the intensity of low-grade peripheral inflammation in healthy individuals (n=56). A two-month training (30 min/day) with a platformer video game resulted in a significantly increased volume of the right hippocampal formation. The number of stressful life events experienced during the past year was associated with less pronounced enlargement of the hippocampus. However, the main predictor of hippocampal volume expansion was the relative peripheral expression of Nuclear Factor-κB (NF-κB), a transcription factor playing a central role in the effect of pro-inflammatory cytokines. Interleukin-6 (IL-6) and C-reactive protein levels were not related to hippocampal plasticity when NF-κB was taken into consideration. These results suggest that more intensive peripheral inflammation is associated with weaker neuronal plasticity during cognitive training. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Mechanical and time-dependent behavior of wood-plastic composites subjected to tension and compression

Treesearch

Scott E. Hamel; John C. Hermanson; Steven M. Cramer

2012-01-01

The thermoplastics within wood—plastic composites (WPCs) are known to experience significant time-dependent deformation or creep. In some formulations, creep deformation can be twice as much as the initial quasi-static strain in as little as 4 days. While extensive work has been done on the creep behavior of pure polymers, little information is available on the...

Manipulation of BDNF signaling modifies the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex.

PubMed

Anomal, Renata; de Villers-Sidani, Etienne; Merzenich, Michael M; Panizzutti, Rogerio

2013-01-01

Sensory experience powerfully shapes cortical sensory representations during an early developmental "critical period" of plasticity. In the rat primary auditory cortex (A1), the experience-dependent plasticity is exemplified by significant, long-lasting distortions in frequency representation after mere exposure to repetitive frequencies during the second week of life. In the visual system, the normal unfolding of critical period plasticity is strongly dependent on the elaboration of brain-derived neurotrophic factor (BDNF), which promotes the establishment of inhibition. Here, we tested the hypothesis that BDNF signaling plays a role in the experience-dependent plasticity induced by pure tone exposure during the critical period in the primary auditory cortex. Elvax resin implants filled with either a blocking antibody against BDNF or the BDNF protein were placed on the A1 of rat pups throughout the critical period window. These pups were then exposed to 7 kHz pure tone for 7 consecutive days and their frequency representations were mapped. BDNF blockade completely prevented the shaping of cortical tuning by experience and resulted in poor overall frequency tuning in A1. By contrast, BDNF infusion on the developing A1 amplified the effect of 7 kHz tone exposure compared to control. These results indicate that BDNF signaling participates in the experience-dependent plasticity induced by pure tone exposure during the critical period in A1.

Dependency Structures for Statistical Machine Translation

ERIC Educational Resources Information Center

Bach, Nguyen

2012-01-01

Dependency structures represent a sentence as a set of dependency relations. Normally the dependency structures from a tree connect all the words in a sentence. One of the most defining characters of dependency structures is the ability to bring long distance dependency between words to local dependency structures. Another the main attraction of…

Transportation and Accumulation of Redox Active Species at the Buried Interfaces of Plasticized Membrane Electrodes.

PubMed

Sohail, Manzar; De Marco, Roland; Jarolímová, Zdeňka; Pawlak, Marcin; Bakker, Eric; He, Ning; Latonen, Rose-Marie; Lindfors, Tom; Bobacka, Johan

2015-09-29

The transportation and accumulation of redox active species at the buried interface between glassy carbon electrodes and plasticized polymeric membranes have been studied using synchrotron radiation X-ray photoelectron spectroscopy (SR-XPS), near edge X-ray absorption fine structure (NEXAFS), in situ electrochemical Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy, cyclic voltammetry (CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). Ferrocene tagged poly(vinyl chloride) [FcPVC], ferrocene (Fc), and its derivatives together with tetracyanoquinodimethane (TCNQ) doped plasticized polymeric membrane electrodes have been investigated, so as to extend the study of the mechanism of this reaction chemistry to different time scales (both small and large molecules with variable diffusion coefficients) using a range of complementary electrochemical and surface analysis techniques. This study also provides direct spectroscopic evidence for the transportation and electrochemical reactivity of redox active species, regardless of the size of the electrochemically reactive molecule, at the buried interface of the substrate electrode. With all redox dopants, when CA electrolysis was performed, redox active species were undetectable (<1 wt % of signature elements or below the detection limit of SR-XPS and NEXAFS) in the outermost surface layers of the membrane, while a high concentration of redox species was located at the electrode substrate as a consequence of the deposition of the reaction product (Fc(+)-anion complex) at the buried interface between the electrode and the membrane. This reaction chemistry for redox active species within plasticized polymeric membranes may be useful in the fashioning of multilayered polymeric devices (e.g., chemical sensors, organic electronic devices, protective laminates, etc.) based on an electrochemical tunable deposition of redox molecules at the buried substrate electrode beneath

The Corticohippocampal Circuit, Synaptic Plasticity, and Memory

PubMed Central

Basu, Jayeeta; Siegelbaum, Steven A.

2015-01-01

Synaptic plasticity serves as a cellular substrate for information storage in the central nervous system. The entorhinal cortex (EC) and hippocampus are interconnected brain areas supporting basic cognitive functions important for the formation and retrieval of declarative memories. Here, we discuss how information flow in the EC–hippocampal loop is organized through circuit design. We highlight recently identified corticohippocampal and intrahippocampal connections and how these long-range and local microcircuits contribute to learning. This review also describes various forms of activity-dependent mechanisms that change the strength of corticohippocampal synaptic transmission. A key point to emerge from these studies is that patterned activity and interaction of coincident inputs gives rise to associational plasticity and long-term regulation of information flow. Finally, we offer insights about how learning-related synaptic plasticity within the corticohippocampal circuit during sensory experiences may enable adaptive behaviors for encoding spatial, episodic, social, and contextual memories. PMID:26525152

Estrogenic activities of chemicals related to food contact plastics and rubbers tested by the yeast two-hybrid assay.

PubMed

Ogawa, Yuko; Kawamura, Yoko; Wakui, Chiseko; Mutsuga, Motoh; Nishimura, Tetsuji; Tanamoto, Kenichi

2006-04-01

Food contact plastics and rubbers possibly contain many kinds of chemicals such as monomers, oligomers, additives, degradation products of polymers and additives, and impurities. Among them, bisphenol A, nonylphenol, benzylbutyl phthalate, styrene oligomers and hydroxylated benzophenones have been reported to possess estrogenic activities. In this study, other chemicals related to food contact plastics and rubbers, and their metabolites induced by the S9-mixture were tested for their estrogenic activities using the yeast two-hybrid assay. Among the 150 chemicals, 10 chemicals such as bis(4-hydroxyphenyl) methane, 4-cyclohexylphenol, 4-phenylphenol, 4,4'-isopropylidenediphenol alkylphosphite, two type of styrenated phenol (including mono type), tris(nonylphenyl) phosphite, 2,2'-dihydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxybenzophenone and 2,4-diphenyl-4-methyl-1-pentene, their metabolites and the metabolites of 6 other chemicals, such as 2-(phenylmethyl) phenol, styrenated phenol (di and tri type), 1-(N-phenylamino)naphthalene, 4-tert-butylphenylsalicylate, nonylphenol ethoxylates and 2-methyl-6-tert-butylphenol, displayed estrogenic activities. All of them contained a phenol group in their chemical structures or formed one easily by hydrolysis or metabolism. However, most of the chemicals related to food contact plastics and rubbers, and their metabolites did not show any estrogenicity.

Effect of the conditions of prepreg preparation on the strength of structural plastics

NASA Astrophysics Data System (ADS)

Zaborskaya, L. V.; Yurkevich, O. R.

1995-05-01

A study is made of the effect of the temperature and duration of heat treatment of polymer composite prepregs on their strength. It is established that heat treatment under conditions ensuring close to maximal adhesive interaction between the components of the prepreg and subsequent shaping makes it possible to more than double the strength of the plastic (Table 1), A new approach is proposed to optimizing the conditions of formation of structural plastics.

A model of human motor sequence learning explains facilitation and interference effects based on spike-timing dependent plasticity.

PubMed

Wang, Quan; Rothkopf, Constantin A; Triesch, Jochen

2017-08-01

The ability to learn sequential behaviors is a fundamental property of our brains. Yet a long stream of studies including recent experiments investigating motor sequence learning in adult human subjects have produced a number of puzzling and seemingly contradictory results. In particular, when subjects have to learn multiple action sequences, learning is sometimes impaired by proactive and retroactive interference effects. In other situations, however, learning is accelerated as reflected in facilitation and transfer effects. At present it is unclear what the underlying neural mechanism are that give rise to these diverse findings. Here we show that a recently developed recurrent neural network model readily reproduces this diverse set of findings. The self-organizing recurrent neural network (SORN) model is a network of recurrently connected threshold units that combines a simplified form of spike-timing dependent plasticity (STDP) with homeostatic plasticity mechanisms ensuring network stability, namely intrinsic plasticity (IP) and synaptic normalization (SN). When trained on sequence learning tasks modeled after recent experiments we find that it reproduces the full range of interference, facilitation, and transfer effects. We show how these effects are rooted in the network's changing internal representation of the different sequences across learning and how they depend on an interaction of training schedule and task similarity. Furthermore, since learning in the model is based on fundamental neuronal plasticity mechanisms, the model reveals how these plasticity mechanisms are ultimately responsible for the network's sequence learning abilities. In particular, we find that all three plasticity mechanisms are essential for the network to learn effective internal models of the different training sequences. This ability to form effective internal models is also the basis for the observed interference and facilitation effects. This suggests that STDP, IP, and SN

State of the Science White Paper: Effects of Plastics Pollution on Aquatic Life and Aquatic-Dependent Wildlife

EPA Pesticide Factsheets

This document is a state-of-the-science review – one that summarizes available scientific information on the effects of chemicals associated with plastic pollution and their potential impacts on aquatic life and aquatic-dependent wildlife.

Functional consequences of experience-dependent plasticity on tactile perception following perceptual learning

PubMed Central

Trzcinski, Natalie K; Gomez-Ramirez, Manuel; Hsiao, Steven S.

2016-01-01

Continuous training enhances perceptual discrimination and promotes neural changes in areas encoding the experienced stimuli. This type of experience-dependent plasticity has been demonstrated in several sensory and motor systems. Particularly, non-human primates trained to detect consecutive tactile bar indentations across multiple digits showed expanded excitatory receptive fields (RFs) in somatosensory cortex. However, the perceptual implications of these anatomical changes remain undetermined. Here, we trained human participants for nine days on a tactile task that promoted expansion of multi-digit RFs. Participants were required to detect consecutive indentations of bar stimuli spanning multiple digits. Throughout the training regime we tracked participants’ discrimination thresholds on spatial (grating orientation) and temporal tasks on the trained and untrained hands in separate sessions. We hypothesized that training on the multi-digit task would decrease perceptual thresholds on tasks that require stimulus processing across multiple digits, while also increasing thresholds on tasks requiring discrimination on single digits. We observed an increase in orientation thresholds on a single-digit. Importantly, this effect was selective for the stimulus orientation and hand used during multi-digit training. We also found that temporal acuity between digits improved across trained digits, suggesting that discriminating the temporal order of multi-digit stimuli can transfer to temporal discrimination of other tactile stimuli. These results suggest that experience-dependent plasticity following perceptual learning improves and interferes with tactile abilities in manners predictive of the task and stimulus features used during training. PMID:27422224

Structural basis for Mob1-dependent activation of the core Mst–Lats kinase cascade in Hippo signaling

DOE PAGES

Ni, Lisheng; Zheng, Yonggang; Hara, Mayuko; ...

2015-06-24

The Mst–Lats kinase cascade is central to the Hippo tumor-suppressive pathway that controls organ size and tissue homeostasis. The adaptor protein Mob1 promotes Lats activation by Mst, but the mechanism remains unknown. Here, we show that human Mob1 binds to autophosphorylated docking motifs in active Mst2. This binding enables Mob1 phosphorylation by Mst2. Phosphorylated Mob1 undergoes conformational activation and binds to Lats1. We determine the crystal structures of phospho-Mst2–Mob1 and phospho-Mob1–Lats1 complexes, revealing the structural basis of both phosphorylation-dependent binding events. Further biochemical and functional analyses demonstrate that Mob1 mediates Lats1 activation through dynamic scaffolding and allosteric mechanisms. Thus, Mob1more » acts as a phosphorylation-regulated coupler of kinase activation by virtue of its ability to engage multiple ligands. We propose that stepwise, phosphorylation-triggered docking interactions of nonkinase elements enhance the specificity and robustness of kinase signaling cascades.« less

Plasticization effect of triacetin on structure and properties of starch ester film.

PubMed

Zhu, Jie; Li, Xiaoxi; Huang, Chen; Chen, Ling; Li, Lin

2013-05-15

The aim of this work was to evaluate the plasticizing effect of triacetin on the structure and properties of starch ester film and further establish the structure-property relationships. The presence of triacetin resulted in multiple structure changes of the film. The mobility of macromolecular chain was increased to form scattered crystallite during the film formation process. The amorphous region was enlarged to contain more triacetin squeezed from crystalline region. The plasticization of triacetin and restriction of crystallite oppositely influenced the mobility of macromolecular chains in different regions. The thermal stability of triacetin changed along with its fluctuant interaction with macromolecules. Comparatively, the enhanced ether bond and the restriction from crystalline regions on the mobility of the amorphous chain consequently improved the thermal stability of the film matrix. The interaction between triacetin and starch ester was essential to film forming but unexpectedly lowered the triacetin stability. Copyright © 2013 Elsevier Ltd. All rights reserved.

Astrocyte and Neuronal Plasticity in the Somatosensory System

PubMed Central

Sims, Robert E.; Butcher, John B.; Parri, H. Rheinallt; Glazewski, Stanislaw

2015-01-01

Changing the whisker complement on a rodent's snout can lead to two forms of experience-dependent plasticity (EDP) in the neurons of the barrel cortex, where whiskers are somatotopically represented. One form, termed coding plasticity, concerns changes in synaptic transmission and connectivity between neurons. This is thought to underlie learning and memory processes and so adaptation to a changing environment. The second, called homeostatic plasticity, serves to maintain a restricted dynamic range of neuronal activity thus preventing its saturation or total downregulation. Current explanatory models of cortical EDP are almost exclusively neurocentric. However, in recent years, increasing evidence has emerged on the role of astrocytes in brain function, including plasticity. Indeed, astrocytes appear as necessary partners of neurons at the core of the mechanisms of coding and homeostatic plasticity recorded in neurons. In addition to neuronal plasticity, several different forms of astrocytic plasticity have recently been discovered. They extend from changes in receptor expression and dynamic changes in morphology to alteration in gliotransmitter release. It is however unclear how astrocytic plasticity contributes to the neuronal EDP. Here, we review the known and possible roles for astrocytes in the barrel cortex, including its plasticity. PMID:26345481

A simplified method for elastic-plastic-creep structural analysis

NASA Technical Reports Server (NTRS)

Kaufman, A.

1984-01-01

A simplified inelastic analysis computer program (ANSYPM) was developed for predicting the stress-strain history at the critical location of a thermomechanically cycled structure from an elastic solution. The program uses an iterative and incremental procedure to estimate the plastic strains from the material stress-strain properties and a plasticity hardening model. Creep effects are calculated on the basis of stress relaxation at constant strain, creep at constant stress or a combination of stress relaxation and creep accumulation. The simplified method was exercised on a number of problems involving uniaxial and multiaxial loading, isothermal and nonisothermal conditions, dwell times at various points in the cycles, different materials and kinematic hardening. Good agreement was found between these analytical results and nonlinear finite element solutions for these problems. The simplified analysis program used less than 1 percent of the CPU time required for a nonlinear finite element analysis.

A simplified method for elastic-plastic-creep structural analysis

NASA Technical Reports Server (NTRS)

Kaufman, A.

1985-01-01

A simplified inelastic analysis computer program (ANSYPM) was developed for predicting the stress-strain history at the critical location of a thermomechanically cycled structure from an elastic solution. The program uses an iterative and incremental procedure to estimate the plastic strains from the material stress-strain properties and a plasticity hardening model. Creep effects are calculated on the basis of stress relaxation at constant strain, creep at constant stress or a combination of stress relaxation and creep accumulation. The simplified method was exercised on a number of problems involving uniaxial and multiaxial loading, isothermal and nonisothermal conditions, dwell times at various points in the cycles, different materials and kinematic hardening. Good agreement was found between these analytical results and nonlinear finite element solutions for these problems. The simplified analysis program used less than 1 percent of the CPU time required for a nonlinear finite element analysis.

Antimicrobial activity, cytotoxicity and inflammatory response of novel plastics embedded with silver nanoparticles.

PubMed

Martínez-Gutiérrez, Fidel; Guajardo-Pacheco, Jesús M; Noriega-Trevino, María E; Thi, Emily P; Reiner, Neil; Orrantia, Erasmo; Av-Gay, Yossef; Ruiz, Facundo; Bach, Horacio

2013-03-01

Infections associated with medical devices are an important cause of morbidity and mortality. Microorganisms are responsible for catheter infections that may then result in the local or systemic dissemination of the microorganism into the bloodstream. The aim of this study was to evaluate the antimicrobial activity of silver nanoparticles (AgNPs) embedded in polyurethane plastics, commonly used for catheter fabrication. AgNPs in the range of 25-30 nm were synthesized and embedded in polyurethane plastics at different concentrations. The antimicrobial activities of these plastics were tested against the three pathogenic microorganisms, Escherichia coli, Staphylococcus epidermidis and Candida albicans, frequently associated with catheter infections. The cytotoxicity of the plastics was evaluated on human-derived macrophages using propidium iodide and the secretion of the pro- and anti-inflammatory cytokines IL-6, IL-10 and TNF-a was measured using ELISA. A significant reduction of 6- to 7-log in the number of bacteria was measured, while a reduction of 90% was measured in the case of C. albicans. Neither cytotoxic effect on macrophages nor immunological response was observed. Plastics embedded with AgNPs have great potential to limit microbial colonization of implanted medical devices.

Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Feng; Stanevich, Vitali; Wlodarchak, Nathan

Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central for the complex PP2A regulation and is crucial for broad aspects of cellular function. The crystal structure of PP2A bound to PP2A phosphatase activator (PTPA) and ATPγS reveals that PTPA makes broad contacts with the structural elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA-binding stabilizes the protein fold of apo-PP2A required for activation, and orients ATP phosphoryl groups to bind directly to the PP2A active site. This allows ATP to modulate the metal-binding preferences of the PP2A active site and utilize the PP2A activemore » site for ATP hydrolysis. In vitro, ATP selectively and drastically enhances binding of endogenous catalytic metal ions, which requires ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function in cell proliferation and survival. Our results suggest novel mechanisms of PTPA in PP2A activation with structural economy and a unique ATP-binding pocket that could potentially serve as a specific therapeutic target.« less

Memristive neural network for on-line learning and tracking with brain-inspired spike timing dependent plasticity.

PubMed

Pedretti, G; Milo, V; Ambrogio, S; Carboni, R; Bianchi, S; Calderoni, A; Ramaswamy, N; Spinelli, A S; Ielmini, D

2017-07-13

Brain-inspired computation can revolutionize information technology by introducing machines capable of recognizing patterns (images, speech, video) and interacting with the external world in a cognitive, humanlike way. Achieving this goal requires first to gain a detailed understanding of the brain operation, and second to identify a scalable microelectronic technology capable of reproducing some of the inherent functions of the human brain, such as the high synaptic connectivity (~10 4 ) and the peculiar time-dependent synaptic plasticity. Here we demonstrate unsupervised learning and tracking in a spiking neural network with memristive synapses, where synaptic weights are updated via brain-inspired spike timing dependent plasticity (STDP). The synaptic conductance is updated by the local time-dependent superposition of pre- and post-synaptic spikes within a hybrid one-transistor/one-resistor (1T1R) memristive synapse. Only 2 synaptic states, namely the low resistance state (LRS) and the high resistance state (HRS), are sufficient to learn and recognize patterns. Unsupervised learning of a static pattern and tracking of a dynamic pattern of up to 4 × 4 pixels are demonstrated, paving the way for intelligent hardware technology with up-scaled memristive neural networks.

Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

PubMed Central

Ito, Yuki; Nakamura, Toshiki; Yanagiba, Yukie; Ramdhan, Doni Hikmat; Yamagishi, Nozomi; Naito, Hisao; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

2012-01-01

Dibutylphthalate (DBP), di(2-ethylhexyl)phthalate (DEHP), and di(2-ethylhexyl)adipate (DEHA) are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR) α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα) and humanized PPARα (hPPARα) mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control), 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg), DEHP (977, 1953 mg/kg), and DEHA (926, 1853 mg/kg), respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR) more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR. PMID:22792086

Synaptic Strength Is Bidirectionally Controlled by Opposing Activity-Dependent Regulation of Nedd4-1 and USP8

PubMed Central

Scudder, Samantha L.; Goo, Marisa S.; Cartier, Anna E.; Molteni, Alice; Schwarz, Lindsay A.; Wright, Rebecca

2014-01-01

The trafficking of AMPA receptors (AMPARs) to and from synapses is crucial for synaptic plasticity. Previous work has demonstrated that AMPARs undergo activity-dependent ubiquitination by the E3 ubiquitin ligase Nedd4-1, which promotes their internalization and degradation in lysosomes. Here, we define the molecular mechanisms involved in ubiquitination and deubiquitination of AMPARs. We report that Nedd4-1 is rapidly redistributed to dendritic spines in response to AMPAR activation and not in response to NMDA receptor (NMDAR) activation in cultured rat neurons. In contrast, NMDAR activation directly antagonizes Nedd4-1 function by promoting the deubiquitination of AMPARs. We show that NMDAR activation causes the rapid dephosphorylation and activation of the deubiquitinating enzyme (DUB) USP8. Surface AMPAR levels and synaptic strength are inversely regulated by Nedd4-1 and USP8. Strikingly, we show that homeostatic downscaling of synaptic strength is accompanied by an increase and decrease in Nedd4-1 and USP8 protein levels, respectively. Furthermore, we show that Nedd4-1 is required for homeostatic loss of surface AMPARs and downscaling of synaptic strength. This study provides the first mechanistic evidence for rapid and opposing activity-dependent control of a ubiquitin ligase and DUB at mammalian CNS synapses. We propose that the dynamic regulation of these opposing forces is critical in maintaining synapses and scaling them during homeostatic plasticity. PMID:25505317

Mean-field theory of a plastic network of integrate-and-fire neurons.

PubMed

Chen, Chun-Chung; Jasnow, David

2010-01-01

We consider a noise-driven network of integrate-and-fire neurons. The network evolves as result of the activities of the neurons following spike-timing-dependent plasticity rules. We apply a self-consistent mean-field theory to the system to obtain the mean activity level for the system as a function of the mean synaptic weight, which predicts a first-order transition and hysteresis between a noise-dominated regime and a regime of persistent neural activity. Assuming Poisson firing statistics for the neurons, the plasticity dynamics of a synapse under the influence of the mean-field environment can be mapped to the dynamics of an asymmetric random walk in synaptic-weight space. Using a master equation for small steps, we predict a narrow distribution of synaptic weights that scales with the square root of the plasticity rate for the stationary state of the system given plausible physiological parameter values describing neural transmission and plasticity. The dependence of the distribution on the synaptic weight of the mean-field environment allows us to determine the mean synaptic weight self-consistently. The effect of fluctuations in the total synaptic conductance and plasticity step sizes are also considered. Such fluctuations result in a smoothing of the first-order transition for low number of afferent synapses per neuron and a broadening of the synaptic-weight distribution, respectively.

Correlating Fluorescence and High-Resolution Scanning Electron Microscopy (HRSEM) for the study of GABAA receptor clustering induced by inhibitory synaptic plasticity.

PubMed

Orlando, Marta; Ravasenga, Tiziana; Petrini, Enrica Maria; Falqui, Andrea; Marotta, Roberto; Barberis, Andrea

2017-10-23

Both excitatory and inhibitory synaptic contacts display activity dependent dynamic changes in their efficacy that are globally termed synaptic plasticity. Although the molecular mechanisms underlying glutamatergic synaptic plasticity have been extensively investigated and described, those responsible for inhibitory synaptic plasticity are only beginning to be unveiled. In this framework, the ultrastructural changes of the inhibitory synapses during plasticity have been poorly investigated. Here we combined confocal fluorescence microscopy (CFM) with high resolution scanning electron microscopy (HRSEM) to characterize the fine structural rearrangements of post-synaptic GABA A Receptors (GABA A Rs) at the nanometric scale during the induction of inhibitory long-term potentiation (iLTP). Additional electron tomography (ET) experiments on immunolabelled hippocampal neurons allowed the visualization of synaptic contacts and confirmed the reorganization of post-synaptic GABA A R clusters in response to chemical iLTP inducing protocol. Altogether, these approaches revealed that, following the induction of inhibitory synaptic potentiation, GABA A R clusters increase in size and number at the post-synaptic membrane with no other major structural changes of the pre- and post-synaptic elements.

Neural plasticity and behavior - sixty years of conceptual advances.

PubMed

Sweatt, J David

2016-10-01

This brief review summarizes 60 years of conceptual advances that have demonstrated a role for active changes in neuronal connectivity as a controller of behavior and behavioral change. Seminal studies in the first phase of the six-decade span of this review firmly established the cellular basis of behavior - a concept that we take for granted now, but which was an open question at the time. Hebbian plasticity, including long-term potentiation and long-term depression, was then discovered as being important for local circuit refinement in the context of memory formation and behavioral change and stabilization in the mammalian central nervous system. Direct demonstration of plasticity of neuronal circuit function in vivo, for example, hippocampal neurons forming place cell firing patterns, extended this concept. However, additional neurophysiologic and computational studies demonstrated that circuit development and stabilization additionally relies on non-Hebbian, homoeostatic, forms of plasticity, such as synaptic scaling and control of membrane intrinsic properties. Activity-dependent neurodevelopment was found to be associated with cell-wide adjustments in post-synaptic receptor density, and found to occur in conjunction with synaptic pruning. Pioneering cellular neurophysiologic studies demonstrated the critical roles of transmembrane signal transduction, NMDA receptor regulation, regulation of neural membrane biophysical properties, and back-propagating action potential in critical time-dependent coincidence detection in behavior-modifying circuits. Concerning the molecular mechanisms underlying these processes, regulation of gene transcription was found to serve as a bridge between experience and behavioral change, closing the 'nature versus nurture' divide. Both active DNA (de)methylation and regulation of chromatin structure have been validated as crucial regulators of gene transcription during learning. The discovery of protein synthesis dependence on the

Supervised spike-timing-dependent plasticity: a spatiotemporal neuronal learning rule for function approximation and decisions.

PubMed

Franosch, Jan-Moritz P; Urban, Sebastian; van Hemmen, J Leo

2013-12-01

How can an animal learn from experience? How can it train sensors, such as the auditory or tactile system, based on other sensory input such as the visual system? Supervised spike-timing-dependent plasticity (supervised STDP) is a possible answer. Supervised STDP trains one modality using input from another one as "supervisor." Quite complex time-dependent relationships between the senses can be learned. Here we prove that under very general conditions, supervised STDP converges to a stable configuration of synaptic weights leading to a reconstruction of primary sensory input.

Circadian and Homeostatic Regulation of Structural Synaptic Plasticity in Hypocretin Neurons

PubMed Central

Appelbaum, Lior; Wang, Gordon; Yokogawa, Tohei; Skariah, Gemini M; Smith, Stephen J; Mourrain, Philippe; Mignot, Emmanuel

2010-01-01

Summary Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin (SYP) in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, was found to modulate circadian synaptic changes. In zebrafish, nptx2b is rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity. PMID:20920793

Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons.

PubMed

Appelbaum, Lior; Wang, Gordon; Yokogawa, Tohei; Skariah, Gemini M; Smith, Stephen J; Mourrain, Philippe; Mignot, Emmanuel

2010-10-06

Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, modulates circadian synaptic changes. In zebrafish, nptx2b is a rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity. Copyright © 2010 Elsevier Inc. All rights reserved.

PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity

PubMed Central

Madeo, G.; Schirinzi, T.; Martella, G.; Latagliata, E.C.; Puglisi, F.; Shen, J.; Valente, E.M.; Federici, M.; Mercuri, N.B.; Puglisi-Allegra, S.; Bonsi, P.; Pisani, A.

2014-01-01

Background Homozygous or compound heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene are causative of autosomal recessive, early onset PD. Single heterozygous mutations have been repeatedly detected in a subset of patients as well as in non-affected subjects, and their significance has long been debated. Several neurophysiological studies from non-manifesting PINK1 heterozygotes have shown the existence of neural plasticity abnormalities, indicating the presence of specific endophenotypic traits in the heterozygous state. Methods In the present study, we performed a functional analysis of corticostriatal synaptic plasticity in heterozygous PINK1 knock-out (PINK1+/−) mice by a multidisciplinary approach. Results We found that, despite a normal motor behavior, repetitive activation of cortical inputs to striatal neurons failed to induce long-term potentiation (LTP), whereas long-term depression (LTD) was normal. Although nigral dopaminergic neurons exhibited normal morphological and electrophysiological properties with normal responses to dopamine receptor activation, we measured a significantly lower dopamine release in the striatum of PINK1+/−, compared to control mice, suggesting that a decrease in stimulus-evoked dopamine overflow acts as a major determinant for the LTP deficit. Accordingly, pharmacological agents capable of increasing the availability of dopamine in the synaptic cleft restored a normal LTP in heterozygous mice. Moreover, MAO-B inhibitors rescued a physiological LTP and a normal dopamine release. Conclusions Our results provide novel evidence for striatal plasticity abnormalities even in the heterozygous disease state. These alterations might be considered an endophenotype to this monogenic form of PD, and a valid tool to characterize early disease stage and design possible disease-modifying therapies. PMID:24167038

Plastic strain arrangement in copper single crystals in sliding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chumaevskii, Andrey V., E-mail: tch7av@gmail.com; Lychagin, Dmitry V., E-mail: dvl-tomsk@mail.ru; Tarasov, Sergei Yu., E-mail: tsy@ispms.tsc.ru

2014-11-14

Deformation of tribologically loaded contact zone is one of the wear mechanisms in spite of the fact that no mass loss may occur during this process. Generation of optimal crystallographic orientations of the grains in a polycrystalline materials (texturing) may cause hardening and reducing the deformation wear. To reveal the orientation dependence of an individual gain and simplify the task we use copper single crystals with the orientations of the compression axis along [111] and [110]. The plastic deformation was investigated by means of optical, scanning electron microscopy and EBSD techniques. It was established that at least four different zonesmore » were generated in the course of sliding test, such as non-deformed base metal, plastic deformation layer sliding, crystalline lattice reorientation layer and subsurface grain structure layer. The maximum plastic strain penetration depth was observed on [110]-single crystals. The minimum stability of [111]-crystals with respect to rotation deformation mode as well as activation of shear in the sliding contact plane provide for rotation deformation localization below the worn surface. The high-rate accumulation of misorientations and less strain penetration depth was observed on [111]-crystals as compared to those of [110]-oriented ones.« less

Transition of temporal scaling behavior in percolation assisted shear-branching structure during plastic deformation

DOE PAGES

Ren, Jingli; Chen, Cun; Wang, Gang; ...

2017-03-22

This study explores the temporal scaling behavior induced shear-branching structure in response to variant temperatures and strain rates during plastic deformation of Zr-based bulk metallic glass (BMG). The data analysis based on the compression tests suggests that there are two states of shear-branching structures: the fractal structure with a long-range order at an intermediate temperature of 223 K and a larger strain rate of 2.5 × 10 –2 s –1; the disordered structure dominated at other temperature and strain rate. It can be deduced from the percolation theory that the compressive ductility, ec, can reach the maximum value at themore » intermediate temperature. Furthermore, a dynamical model involving temperature is given for depicting the shear-sliding process, reflecting the plastic deformation has fractal structure at the temperature of 223 K and strain rate of 2.5 × 10 –2 s –1.« less

Functional consequences of experience-dependent plasticity on tactile perception following perceptual learning.

PubMed

Trzcinski, Natalie K; Gomez-Ramirez, Manuel; Hsiao, Steven S

2016-09-01

Continuous training enhances perceptual discrimination and promotes neural changes in areas encoding the experienced stimuli. This type of experience-dependent plasticity has been demonstrated in several sensory and motor systems. Particularly, non-human primates trained to detect consecutive tactile bar indentations across multiple digits showed expanded excitatory receptive fields (RFs) in somatosensory cortex. However, the perceptual implications of these anatomical changes remain undetermined. Here, we trained human participants for 9 days on a tactile task that promoted expansion of multi-digit RFs. Participants were required to detect consecutive indentations of bar stimuli spanning multiple digits. Throughout the training regime we tracked participants' discrimination thresholds on spatial (grating orientation) and temporal tasks on the trained and untrained hands in separate sessions. We hypothesized that training on the multi-digit task would decrease perceptual thresholds on tasks that require stimulus processing across multiple digits, while also increasing thresholds on tasks requiring discrimination on single digits. We observed an increase in orientation thresholds on a single digit. Importantly, this effect was selective for the stimulus orientation and hand used during multi-digit training. We also found that temporal acuity between digits improved across trained digits, suggesting that discriminating the temporal order of multi-digit stimuli can transfer to temporal discrimination of other tactile stimuli. These results suggest that experience-dependent plasticity following perceptual learning improves and interferes with tactile abilities in manners predictive of the task and stimulus features used during training. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Bilateral Activity-Dependent Interactions in the Developing Corticospinal System

PubMed Central

Friel, Kathleen M.; Martin, John H.

2009-01-01

Activity-dependent competition between the corticospinal (CS) systems in each hemisphere drives postnatal development of motor skills and stable CS tract connections with contralateral spinal motor circuits. Unilateral restriction of motor cortex (M1) activity during an early postnatal critical period impairs contralateral visually guided movements later in development and in maturity. Silenced M1 develops aberrant connections with the contralateral spinal cord whereas the initially active M1, in the other hemisphere, develops bilateral connections. In this study, we determined whether the aberrant pattern of CS tract terminations and motor impairments produced by early postnatal M1 activity restriction could be abrogated by reducing activity-dependent synaptic competition from the initially active M1 later in development. We first inactivated M1 unilaterally between postnatal weeks 5–7. We next inactivated M1 on the other side from weeks 7–11 (alternate inactivation), to reduce the competitive advantage that this side may have over the initially inactivated side. Alternate inactivation redirected aberrant contralateral CS tract terminations from the initially silenced M1 to their normal spinal territories and reduced the density of aberrant ipsilateral terminations from the initially active side. Normal movement endpoint control during visually guided locomotion was fully restored. This reorganization of CS terminals reveals an unsuspected late plasticity after the critical period for establishing the pattern of CS terminations in the spinal cord. Our findings show that robust bilateral interactions between the developing CS systems on each side are important for achieving balance between contralateral and ipsilateral CS tract connections and visuomotor control. PMID:17928450

Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.

PubMed

Chen, Kang; Neu, Axel; Howard, Allyson L; Földy, Csaba; Echegoyen, Julio; Hilgenberg, Lutz; Smith, Martin; Mackie, Ken; Soltesz, Ivan

2007-01-03

Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiation in vitro required a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that the in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.

Extraction of temporally correlated features from dynamic vision sensors with spike-timing-dependent plasticity.

PubMed

Bichler, Olivier; Querlioz, Damien; Thorpe, Simon J; Bourgoin, Jean-Philippe; Gamrat, Christian

2012-08-01

A biologically inspired approach to learning temporally correlated patterns from a spiking silicon retina is presented. Spikes are generated from the retina in response to relative changes in illumination at the pixel level and transmitted to a feed-forward spiking neural network. Neurons become sensitive to patterns of pixels with correlated activation times, in a fully unsupervised scheme. This is achieved using a special form of Spike-Timing-Dependent Plasticity which depresses synapses that did not recently contribute to the post-synaptic spike activation, regardless of their activation time. Competitive learning is implemented with lateral inhibition. When tested with real-life data, the system is able to extract complex and overlapping temporally correlated features such as car trajectories on a freeway, after only 10 min of traffic learning. Complete trajectories can be learned with a 98% detection rate using a second layer, still with unsupervised learning, and the system may be used as a car counter. The proposed neural network is extremely robust to noise and it can tolerate a high degree of synaptic and neuronal variability with little impact on performance. Such results show that a simple biologically inspired unsupervised learning scheme is capable of generating selectivity to complex meaningful events on the basis of relatively little sensory experience. Copyright © 2012 Elsevier Ltd. All rights reserved.

Active Well Counting Using New PSD Plastic Detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hausladen, Paul; Newby, Jason; McElroy, Robert Dennis

This report presents results and analysis from a series of proof-of-concept measurements to assess the suitability of segmented detectors constructed from Eljen EJ-299-34 PSD-plastic scintillator with pulse-shape discrimination capability for the purposes of quantifying uranium via active neutron coincidence counting. Present quantification of bulk uranium materials for international safeguards and domestic materials control and accounting relies on active neutron coincidence counting systems, such as the Active Well Coincidence Counter (AWCC) and the Uranium Neutron Coincidence Collar (UNCL), that use moderated He-3 proportional counters along with necessarily low-intensity 241Am(Li) neutron sources. Scintillation-based fast-neutron detectors are a potentially superior technology to themore » existing AWCC and UNCL designs due to their spectroscopic capability and their inherently short neutron coincidence times that largely eliminate random coincidences and enable interrogation by stronger sources. One of the past impediments to the investigation and adoption of scintillation counters for the purpose of quantifying bulk uranium was the commercial availability of scintillators having the necessary neutron-gamma pulse-shape discrimination properties only as flammable liquids. Recently, Eljen EJ-299-34 PSD-plastic scintillator became commercially available. The present work is the first assessment of an array of PSD-plastic detectors for the purposes of quantifying bulk uranium. The detector panel used in the present work was originally built as the focal plane for a fast-neutron imager, but it was repurposed for the present investigation by construction of a stand to support the inner well of an AWCC immediately in front of the detector panel. The detector panel and data acquisition of this system are particularly well suited for performing active-well fast-neutron counting of LEU and HEU samples because the active detector volume is solid, the 241Am

Determination of the diffusion coefficient and solubility of radon in plastics.

PubMed

Pressyanov, D; Georgiev, S; Dimitrova, I; Mitev, K; Boshkova, T

2011-05-01

This paper describes a method for determination of the diffusion coefficient and the solubility of radon in plastics. The method is based on the absorption and desorption of radon in plastics. Firstly, plastic specimens are exposed for controlled time to referent (222)Rn concentrations. After exposure, the activity of the specimens is followed by HPGe gamma spectrometry. Using the mathematical algorithm described in this report and the decrease of activity as a function of time, the diffusion coefficient can be determined. In addition, if the referent (222)Rn concentration during the exposure is known, the solubility of radon can be determined. The algorithm has been experimentally applied for different plastics. The results show that this approach allows the specified quantities to be determined with a rather high accuracy-depending on the quality of the counting equipment, it can be better than 10 %.

Constitutive modeling and structural analysis considering simultaneous phase transformation and plastic yield in shape memory alloys

NASA Astrophysics Data System (ADS)

Hartl, D. J.; Lagoudas, D. C.

2009-10-01

The new developments summarized in this work represent both theoretical and experimental investigations of the effects of plastic strain generation in shape memory alloys (SMAs). Based on the results of SMA experimental characterization described in the literature and additional testing described in this work, a new 3D constitutive model is proposed. This phenomenological model captures both the conventional shape memory effects of pseudoelasticity and thermal strain recovery, and additionally considers the initiation and evolution of plastic strains. The model is numerically implemented in a finite element framework using a return mapping algorithm to solve the constitutive equations at each material point. This combination of theory and implementation is unique in its ability to capture the simultaneous evolution of recoverable transformation strains and irrecoverable plastic strains. The consideration of isotropic and kinematic plastic hardening allows the derivation of a theoretical framework capturing the interactions between irrecoverable plastic strain and recoverable strain due to martensitic transformation. Further, the numerical integration of the constitutive equations is formulated such that objectivity is maintained for SMA structures undergoing moderate strains and large displacements. The implemented model has been used to perform 3D analysis of SMA structural components under uniaxial and bending loads, including a case of local buckling behavior. Experimentally validated results considering simultaneous transformation and plasticity in a bending member are provided, illustrating the predictive accuracy of the model and its implementation.

Dynamic rupture simulations on complex fault zone structures with off-fault plasticity using the ADER-DG method

NASA Astrophysics Data System (ADS)

Wollherr, Stephanie; Gabriel, Alice-Agnes; Igel, Heiner

2015-04-01

zones or branched faults. Studying the interplay of stress conditions and angle dependence of neighbouring branches including inelastic material behaviour and its effects on rupture jumps and seismic activation helps to advance our understanding of earthquake source processes. An application is the simulation of a real large-scale subduction zone scenario including plasticity to validate the coupling of our dynamic rupture calculations to a tsunami model in the framework of the ASCETE project (http://www.ascete.de/). Andrews, D. J. (2005): Rupture dynamics with energy loss outside the slip zone, J. Geophys. Res., 110, B01307. Heinecke, A. (2014), A. Breuer, S. Rettenberger, M. Bader, A.-A. Gabriel, C. Pelties, A. Bode, W. Barth, K. Vaidyanathan, M. Smelyanskiy and P. Dubey: Petascale High Order Dynamic Rupture Earthquake Simulations on Heterogeneous Supercomputers. In Supercomputing 2014, The International Conference for High Performance Computing, Networking, Storage and Analysis. IEEE, New Orleans, LA, USA, November 2014. Roten, D. (2014), K. B. Olsen, S.M. Day, Y. Cui, and D. Fäh: Expected seismic shaking in Los Angeles reduced by San Andreas fault zone plasticity, Geophys. Res. Lett., 41, 2769-2777.

"New" Compounds from Old Plastics: Recycling PET Plastics via Depolymerization. An Activity for the Undergraduate Organic Lab

NASA Astrophysics Data System (ADS)

Kaufman, Don; Wright, Geoff; Kroemer, Ryan; Engel, Josh

1999-11-01

This paper describes work done to develop a meaningful undergraduate organic lab activity that illustrates chemistry of the real world while utilizing reactions typically included in the organic lecture and lab. We show how a common plastic can be converted into several compounds using ester hydrolysis and SN2 reactions. Contributing to the critical shortage of landfill space faced by many communities is the large quantity of plastic refuse. Thus, there is a real need to recycle plastic products. One way to recycle plastics such as polyethyleneterephthalate (PET), the polyester from which numerous consumer products such as 2-liter soda bottles are made, is to depolymerize them and then to use the resulting monomers to produce new products. PET is industrially depolymerized via an acid-catalyzed transesterification reaction conducted under conditions of high temperature and pressure that are not feasible in the undergraduate lab. Despite literature reports that PET is remarkably resistant to hydrolysis, we found that PET can be readily hydrolyzed by refluxing with potassium hydroxide or potassium tert-butoxide in amyl alcohol to give terephthalic acid in high yield. It is then possible to readily synthesize terephthalate diesters via SN2 reactions of ammonium terephthalate salts with alkyl halides. Fischer esterification can also be used to prepare the diesters, but yields are significantly lower.

Short- and long-term functional plasticity of white matter induced by oligodendrocyte depolarization in the hippocampus.

PubMed

Yamazaki, Yoshihiko; Fujiwara, Hiroki; Kaneko, Kenya; Hozumi, Yasukazu; Xu, Ming; Ikenaka, Kazuhiro; Fujii, Satoshi; Tanaka, Kenji F

2014-08-01

Plastic changes in white matter have received considerable attention in relation to normal cognitive function and learning. Oligodendrocytes and myelin, which constitute the white matter in the central nervous system, can respond to neuronal activity with prolonged depolarization of membrane potential and/or an increase in the intracellular Ca(2+) concentration. Depolarization of oligodendrocytes increases the conduction velocity of an action potential along axons myelinated by the depolarized oligodendrocytes, indicating that white matter shows functional plasticity, as well as structural plasticity. However, the properties and mechanism of oligodendrocyte depolarization-induced functional plastic changes in white matter are largely unknown. Here, we investigated the functional plasticity of white matter in the hippocampus using mice with oligodendrocytes expressing channelrhodopsin-2. Using extracellular recordings of compound action potentials at the alveus of the hippocampus, we demonstrated that light-evoked depolarization of oligodendrocytes induced early- and late-onset facilitation of axonal conduction that was dependent on the magnitude of oligodendrocyte depolarization; the former lasted for approximately 10 min, whereas the latter continued for up to 3 h. Using whole-cell recordings from CA1 pyramidal cells and recordings of antidromic action potentials, we found that the early-onset short-lasting component included the synchronization of action potentials. Moreover, pharmacological analysis demonstrated that the activation of Ba(2+) -sensitive K(+) channels was involved in early- and late-onset facilitation, whereas 4-aminopyridine-sensitive K(+) channels were only involved in the early-onset component. These results demonstrate that oligodendrocyte depolarization induces short- and long-term functional plastic changes in the white matter of the hippocampus and plays active roles in brain functions. © 2014 Wiley Periodicals, Inc.

Signal processing in local neuronal circuits based on activity-dependent noise and competition

NASA Astrophysics Data System (ADS)

Volman, Vladislav; Levine, Herbert

2009-09-01

We study the characteristics of weak signal detection by a recurrent neuronal network with plastic synaptic coupling. It is shown that in the presence of an asynchronous component in synaptic transmission, the network acquires selectivity with respect to the frequency of weak periodic stimuli. For nonperiodic frequency-modulated stimuli, the response is quantified by the mutual information between input (signal) and output (network's activity) and is optimized by synaptic depression. Introducing correlations in signal structure resulted in the decrease in input-output mutual information. Our results suggest that in neural systems with plastic connectivity, information is not merely carried passively by the signal; rather, the information content of the signal itself might determine the mode of its processing by a local neuronal circuit.

Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

PubMed Central

Nabel, Elisa M.; Morishita, Hirofumi

2013-01-01

Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development – the preeminent model of experience-dependent critical period plasticity-actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins – endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions. PMID:24273519

Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

PubMed

Gur, Rotem; Tendler, Alex; Wagner, Shlomo

2014-09-01

Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The role of sleep in regulating structural plasticity and synaptic strength: Implications for memory and cognitive function.

PubMed

Raven, Frank; Van der Zee, Eddy A; Meerlo, Peter; Havekes, Robbert

2018-06-01

Dendritic spines are the major sites of synaptic transmission in the central nervous system. Alterations in the strength of synaptic connections directly affect the neuronal communication, which is crucial for brain function as well as the processing and storage of information. Sleep and sleep loss bidirectionally alter structural plasticity, by affecting spine numbers and morphology, which ultimately can affect the functional output of the brain in terms of alertness, cognition, and mood. Experimental data from studies in rodents suggest that sleep deprivation may impact structural plasticity in different ways. One of the current views, referred to as the synaptic homeostasis hypothesis, suggests that wake promotes synaptic potentiation whereas sleep facilitates synaptic downscaling. On the other hand, several studies have now shown that sleep deprivation can reduce spine density and attenuate synaptic efficacy in the hippocampus. These data are the basis for the view that sleep promotes hippocampal structural plasticity critical for memory formation. Altogether, the impact of sleep and sleep loss may vary between regions of the brain. A better understanding of the role that sleep plays in regulating structural plasticity may ultimately lead to novel therapeutic approaches for brain disorders that are accompanied by sleep disturbances and sleep loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural and Functional Plasticity within the Nucleus Accumbens and Prefrontal Cortex Associated with Time-Dependent Increases in Food Cue-Seeking Behavior.

PubMed

Dingess, Paige M; Darling, Rebecca A; Derman, Rifka C; Wulff, Shaun S; Hunter, Melissa L; Ferrario, Carrie R; Brown, Travis E

2017-11-01

Urges to consume food can be driven by stimuli in the environment that are associated with previous food experience. Identifying adaptations within brain reward circuits that facilitate cue-induced food seeking is critical for understanding and preventing the overconsumption of food and subsequent weight gain. Utilizing electrophysiological, biochemical, and DiI labeling, we examined functional and structural changes in the nucleus accumbens (NAc) and prefrontal cortex (PFC) associated with time-dependent increases in food craving ('incubation of craving'). Rats self-administered 60% high fat or chow 45 mg pellets and were then tested for incubation of craving either 1 or 30 days after training. High fat was chosen for comparison to determine whether palatability differentially affected incubation and/or plasticity. Rats showed robust incubation of craving for both food rewards, although responding for cues previously associated with high fat was greater than chow at both 1 and 30 days. In addition, previous experience with high-fat consumption reduced dendritic spine density in the PFC at both time points. In contrast, incubation was associated with an increase in NAc spine density and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated transmission at 30 days in both groups. Finally, incubation of craving for chow and high fat was accompanied by an increase in calcium-permeable and calcium-impermeable AMPARs, respectively. Our results suggest that incubation of food craving alters brain reward circuitry and macronutrient composition specifically induces cortical changes in a way that may facilitate maladaptive food-seeking behaviors.

Biodegradability of plastics.

PubMed

Tokiwa, Yutaka; Calabia, Buenaventurada P; Ugwu, Charles U; Aiba, Seiichi

2009-08-26

Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed.

Biodegradability of Plastics

PubMed Central

Tokiwa, Yutaka; Calabia, Buenaventurada P.; Ugwu, Charles U.; Aiba, Seiichi

2009-01-01

Plastic is a broad name given to different polymers with high molecular weight, which can be degraded by various processes. However, considering their abundance in the environment and their specificity in attacking plastics, biodegradation of plastics by microorganisms and enzymes seems to be the most effective process. When plastics are used as substrates for microorganisms, evaluation of their biodegradability should not only be based on their chemical structure, but also on their physical properties (melting point, glass transition temperature, crystallinity, storage modulus etc.). In this review, microbial and enzymatic biodegradation of plastics and some factors that affect their biodegradability are discussed. PMID:19865515

Synaptic plasticity and levodopa-induced dyskinesia: electrophysiological and structural abnormalities.

PubMed

Picconi, Barbara; De Leonibus, Elvira; Calabresi, Paolo

2018-02-28

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons located in the midbrain. The gold-standard therapy for PD is the restoration of dopamine (DA) levels through the chronic administration of the DA precursor levodopa (L-DOPA). Although levodopa therapy is the main therapeutic approach for PD, its use is limited by the development of very disabling dyskinetic movements, mainly due to the fluctuation of DA cerebral content. Experimental animal models of PD identified in DA D1/ERK-signaling pathway aberrant activation, occurring in striatal projection neurons, coupled with structural spines abnormalities, the molecular and neuronal basis of L-DOPA-induced dyskinesia (LIDs) occurrence. Different electrophysiological approaches allowed the identification of  the alteration of homeostatic structural and synaptic changes, the neuronal bases of LIDs either in vivo in parkinsonian patients or in vitro in experimental animals. Here, we report the most recent studies showing electrophysiological and morphological evidence of aberrant synaptic plasticity in parkinsonian patients during LIDs in different basal ganglia nuclei and also in cortical transmission, accounting for the complexity of the synaptic changes during dyskinesias. All together, these studies suggest that LIDs are associated with a loss of homeostatic synaptic mechanisms.

Plastic Jellyfish.

ERIC Educational Resources Information Center

Moseley, Christine

2000-01-01

Presents an environmental science activity designed to enhance students' awareness of the hazards of plastic waste for wildlife in aquatic environments. Discusses how students can take steps to reduce the effects of plastic waste. (WRM)

All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis.

PubMed

Vivar, Carmen; Potter, Michelle C; van Praag, Henriette

2013-01-01

Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF).

Neuropeptide Signaling Networks and Brain Circuit Plasticity.

PubMed

McClard, Cynthia K; Arenkiel, Benjamin R

2018-01-01

The brain is a remarkable network of circuits dedicated to sensory integration, perception, and response. The computational power of the brain is estimated to dwarf that of most modern supercomputers, but perhaps its most fascinating capability is to structurally refine itself in response to experience. In the language of computers, the brain is loaded with programs that encode when and how to alter its own hardware. This programmed "plasticity" is a critical mechanism by which the brain shapes behavior to adapt to changing environments. The expansive array of molecular commands that help execute this programming is beginning to emerge. Notably, several neuropeptide transmitters, previously best characterized for their roles in hypothalamic endocrine regulation, have increasingly been recognized for mediating activity-dependent refinement of local brain circuits. Here, we discuss recent discoveries that reveal how local signaling by corticotropin-releasing hormone reshapes mouse olfactory bulb circuits in response to activity and further explore how other local neuropeptide networks may function toward similar ends.

Plasticized poly(lactic acid)-poly(hydroxybutyrate) (PLA-PHB) blends incorporated with catechin intended for active food-packaging applications.

PubMed

Arrieta, Marina Patricia; Castro-López, María del Mar; Rayón, Emilio; Barral-Losada, Luis Fernando; López-Vilariño, José Manuel; López, Juan; González-Rodríguez, María Victoria

2014-10-15

Active biobased packaging materials based on poly(lactic acid)-poly(hydroxybutyrate) (PLA-PHB) blends were prepared by melt blending and fully characterized. Catechin incorporation, as antioxidant compound, enhanced the thermal stability, whereas its release was improved by the addition of acetyl(tributyl citrate) (ATBC) as plasticizer. Whereas the incorporation of ATBC resulted in a reduction of elastic modulus and hardness, catechin addition produced more rigid materials due to hydrogen-bonding interactions between catechin hydroxyl groups and carbonyl groups of PLA and PHB. The quantification of catechin released into a fatty food simulant and the antioxidant effectiveness after the release process were demonstrated. The effect of the materials' exposure to a food simulant was also investigated. PHB-added materials maintained their structural and mechanical properties after 10 days in a test medium that represents the worst foreseeable conditions of the intended use. Thus, plasticized PLA-PHB blends with catechin show their potential as biobased active packaging for fatty food.

The Thermal and Microstructural Effect of Plasticizing HMX-Nitrocellulose Composites

DOE PAGES

Yeager, John David; Watkins, Erik Benjamin; Duque, Amanda Lynn; ...

2017-03-15

Thermal ignition via self-heating (cook-off) of cyclotetramethylene-tetranitramine (HMX)-containing plastic-bonded explosives (PBXs) is driven by the β → δ phase transition in the HMX, which is affected if not dominated by microstructure. Here, we studied the HMX-binder interface and phase transition for several variations of PBX 9404 (HMX with plasticized nitrocellulose [NC] binder). Neutron reflectometry was used to examine the interface under several conditions—pristine, after aging, and after thermal treatment. The initial interfacial structure depended on the plasticizer, but the interface homogenized over time. Thermal and optical analyses showed that all formulated materials had higher transition temperatures than neat HMX. Thismore » effect increased with NC content.« less

The Thermal and Microstructural Effect of Plasticizing HMX-Nitrocellulose Composites

NASA Astrophysics Data System (ADS)

Yeager, John D.; Watkins, Erik B.; Higginbotham Duque, Amanda L.; Majewski, Jaroslaw

2018-01-01

Thermal ignition via self-heating (cook-off) of cyclotetramethylene-tetranitramine (HMX)-containing plastic-bonded explosives (PBXs) is driven by the β → δ phase transition in the HMX, which is affected if not dominated by microstructure. Here, the HMX-binder interface and phase transition were studied for several variations of PBX 9404 (HMX with plasticized nitrocellulose [NC] binder). Neutron reflectometry was used to examine the interface under several conditions-pristine, after aging, and after thermal treatment. The initial interfacial structure depended on the plasticizer, but the interface homogenized over time. Thermal and optical analyses showed that all formulated materials had higher transition temperatures than neat HMX. This effect increased with NC content.

Learning-dependent plasticity with and without training in the human brain.

PubMed

Zhang, Jiaxiang; Kourtzi, Zoe

2010-07-27

Long-term experience through development and evolution and shorter-term training in adulthood have both been suggested to contribute to the optimization of visual functions that mediate our ability to interpret complex scenes. However, the brain plasticity mechanisms that mediate the detection of objects in cluttered scenes remain largely unknown. Here, we combine behavioral and functional MRI (fMRI) measurements to investigate the human-brain mechanisms that mediate our ability to learn statistical regularities and detect targets in clutter. We show two different routes to visual learning in clutter with discrete brain plasticity signatures. Specifically, opportunistic learning of regularities typical in natural contours (i.e., collinearity) can occur simply through frequent exposure, generalize across untrained stimulus features, and shape processing in occipitotemporal regions implicated in the representation of global forms. In contrast, learning to integrate discontinuities (i.e., elements orthogonal to contour paths) requires task-specific training (bootstrap-based learning), is stimulus-dependent, and enhances processing in intraparietal regions implicated in attention-gated learning. We propose that long-term experience with statistical regularities may facilitate opportunistic learning of collinear contours, whereas learning to integrate discontinuities entails bootstrap-based training for the detection of contours in clutter. These findings provide insights in understanding how long-term experience and short-term training interact to shape the optimization of visual recognition processes.

Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

PubMed Central

Posfai, Eszter; Petropoulos, Sophie; de Barros, Flavia Regina Oliveira; Schell, John Paul; Jurisica, Igor; Sandberg, Rickard; Lanner, Fredrik; Rossant, Janet

2017-01-01

The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene expression changes are still unclear. Single-cell RNA sequencing during lineage segregation revealed that the TE transcriptional profile stabilizes earlier than the ICM and prior to blastocyst formation. Using quantitative Cdx2-eGFP expression as a readout of Hippo signaling activity, we assessed the experimental potential of individual blastomeres based on their level of Cdx2-eGFP expression and correlated potential with gene expression dynamics. We find that TE specification and commitment coincide and occur at the time of transcriptional stabilization, whereas ICM cells still retain the ability to regenerate TE up to the early blastocyst stage. Plasticity of both lineages is coincident with their window of sensitivity to Hippo signaling. DOI: http://dx.doi.org/10.7554/eLife.22906.001 PMID:28226240

Structural explanation for the role of Mn2+ in the activity of phi6 RNA-dependent RNA polymerase.

PubMed

Poranen, Minna M; Salgado, Paula S; Koivunen, Minni R L; Wright, Sam; Bamford, Dennis H; Stuart, David I; Grimes, Jonathan M

2008-11-01

The biological role of manganese (Mn(2+)) has been a long-standing puzzle, since at low concentrations it activates several polymerases whilst at higher concentrations it inhibits. Viral RNA polymerases possess a common architecture, reminiscent of a closed right hand. The RNA-dependent RNA polymerase (RdRp) of bacteriophage 6 is one of the best understood examples of this important class of polymerases. We have probed the role of Mn(2+) by biochemical, biophysical and structural analyses of the wild-type enzyme and of a mutant form with an altered Mn(2+)-binding site (E491 to Q). The E491Q mutant has much reduced affinity for Mn(2+), reduced RNA binding and a compromised elongation rate. Loss of Mn(2+) binding structurally stabilizes the enzyme. These data and a re-examination of the structures of other viral RNA polymerases clarify the role of manganese in the activation of polymerization: Mn(2+) coordination of a catalytic aspartate is necessary to allow the active site to properly engage with the triphosphates of the incoming NTPs. The structural flexibility caused by Mn(2+) is also important for the enzyme dynamics, explaining the requirement for manganese throughout RNA polymerization.

Sleep loss and structural plasticity.

PubMed

Areal, Cassandra C; Warby, Simon C; Mongrain, Valérie

2017-06-01

Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

A temperature dependent cyclic plasticity model for hot work tool steel including particle coarsening

NASA Astrophysics Data System (ADS)

Jilg, Andreas; Seifert, Thomas

2018-05-01

Hot work tools are subjected to complex thermal and mechanical loads during hot forming processes. Locally, the stresses can exceed the material's yield strength in highly loaded areas as e.g. in small radii in die cavities. To sustain the high loads, the hot forming tools are typically made of martensitic hot work steels. While temperatures for annealing of the tool steels usually lie in the range between 400 and 600 °C, the steels may experience even higher temperatures during hot forming, resulting in softening of the material due to coarsening of strengthening particles. In this paper, a temperature dependent cyclic plasticity model for the martensitic hot work tool steel 1.2367 (X38CrMoV5-3) is presented that includes softening due to particle coarsening and that can be applied in finite-element calculations to assess the effect of softening on the thermomechanical fatigue life of hot work tools. To this end, a kinetic model for the evolution of the mean size of secondary carbides based on Ostwald ripening is coupled with a cyclic plasticity model with kinematic hardening. Mechanism-based relations are developed to describe the dependency of the mechanical properties on carbide size and temperature. The material properties of the mechanical and kinetic model are determined on the basis of tempering hardness curves as well as monotonic and cyclic tests.

Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning

PubMed Central

Barre, Alexander; Berthoux, Coralie; De Bundel, Dimitri; Valjent, Emmanuel; Bockaert, Joël; Marin, Philippe; Bécamel, Carine

2016-01-01

Higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (PFC). Alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. Prefrontal serotonin (5-HT)2A receptors play an essential role in cortical network activity, but the mechanism underlying their modulation of glutamatergic transmission and plasticity at thalamocortical synapses remains largely unexplored. Here, we show that 5-HT2A receptor activation enhances NMDA transmission and gates the induction of temporal-dependent plasticity mediated by NMDA receptors at thalamocortical synapses in acute PFC slices. Expressing 5-HT2A receptors in the mediodorsal thalamus (presynaptic site) of 5-HT2A receptor-deficient mice, but not in the PFC (postsynaptic site), using a viral gene-delivery approach, rescued the otherwise absent potentiation of NMDA transmission, induction of temporal plasticity, and deficit in associative memory. These results provide, to our knowledge, the first physiological evidence of a role of presynaptic 5-HT2A receptors located at thalamocortical synapses in the control of thalamofrontal connectivity and the associated cognitive functions. PMID:26903620

The influences of soil and nearby structures on dispersion characteristics of wave propagating along buried plastic pipes

NASA Astrophysics Data System (ADS)

Liu, Shuyong; Jiang, J.; Parr, Nicola

2016-09-01

Water loss in distribution systems is a global problem for the water industry and governments. According to the international water supply association (IWSA), as a result of leaks from distribution pipes, 20% to 30% of water is lost while in transit from treatment plants to consumers. Although governments have tried to push the water industry to reduce the water leaks, a lot of experts have pointed out that a wide use of plastic pipes instead of metal pipes in recent years has caused difficulties in the detection of leaks using current acoustic technology. Leaks from plastic pipes are much quieter than traditional metal pipes and comparing to metal pipes the plastic pipes have very different coupling characteristics with soil, water and surrounding structures, such as other pipes, road surface and building foundations. The dispersion characteristics of wave propagating along buried plastic pipes are investigated in this paper using finite element and boundary element based models. Both empty and water- filled pipes were considered. Influences from nearby pipes and building foundations were carefully studied. The results showed that soil condition and nearby structures have significant influences on the dispersion characteristics of wave propagating along buried plastic pipes.

Different patterns of motor activity induce differential plastic changes in pyramidal neurons in the motor cortex of rats: A Golgi study.

PubMed

Vázquez-Hernández, Nallely; González-Tapia, Diana C; Martínez-Torres, Nestor I; González-Tapia, David; González-Burgos, Ignacio

2017-09-14

Rehabilitation is a process which favors recovery after brain damage involving motor systems, and neural plasticity is the only real resource the brain has for inducing neurobiological events in order to bring about re-adaptation. Rats were placed on a treadmill and made to walk, in different groups, at different velocities and with varying degrees of inclination. Plastic changes in the spines of the apical and basal dendrites of fifth-layer pyramidal neurons in the motor cortices of the rats were detected after study with the Golgi method. Numbers of dendritic spines increased in the three experimental groups, and thin, mushroom, stubby, wide, and branched spines increased or decreased in proportion depending on the motor demands made of each group. Along with the numerical increase of spines, the present findings provide evidence that dendritic spines' geometrical plasticity is involved in the differential performance of motor activity. Copyright © 2017 Elsevier B.V. All rights reserved.

The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

PubMed Central

Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

2015-01-01

The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

Structures of almond hydroxynitrile lyase isoenzyme 5 provide a rationale for the lack of oxidoreductase activity in flavin dependent HNLs.

PubMed

Pavkov-Keller, Tea; Bakhuis, Janny; Steinkellner, Georg; Jolink, Fenneke; Keijmel, Esther; Birner-Gruenberger, Ruth; Gruber, Karl

2016-10-10

Hydroxynitrile lyases (HNLs) catalyze the asymmetric addition of HCN to aldehydes producing enantiomerically pure cyanohydrins. These enzymes can be heterologously expressed in large quantities making them interesting candidates for industrial applications. The HNLs from Rosaceae evolved from flavin dependent dehydrogenase/oxidase structures. Here we report the high resolution X-ray structure of the highly glycosylated Prunus amygdalus HNL isoenzyme5 (PaHNL5 V317A) expressed in Aspergillus niger and its complex with benzyl alcohol. A comparison with the structure of isoenzyme PaHNL1 indicates a higher accessibility to the active site and a larger cavity for PaHNL5. Additionally, the PaHNL5 complex structure with benzyl alcohol was compared with the structurally related aryl-alcohol oxidase (AAO). Even though both enzymes contain an FAD-cofactor and histidine residues at crucial positions in the active site, PaHNL5 lacks the oxidoreductase activity. The structures indicate that in PaHNLs benzyl alcohol is bound too far away from the FAD cofactor in order to be oxidized. Copyright © 2016 Elsevier B.V. All rights reserved.

Self-Assembled Ag-MXA Superclusters with Structure-Dependent Mechanical Properties.

PubMed

Qin, Xiaoyun; Luo, Dan; Xue, Zhenjie; Song, Qian; Wang, Tie

2018-03-01

The low elastic modulus and time-consuming formation process represent the major challenges that impede the penetration of nanoparticle superstructures into daily life applications. As observed in the molecular or atomic crystals, more effective interactions between adjacent nanoparticles would introduce beneficial features to assemblies enabling optimized mechanical properties. Here, a straightforward synthetic strategy is showed that allows fast and scalable fabrication of 2D Ag-mercaptoalkyl acid superclusters of either hexagonal or lamellar topology. Remarkably, these ordered superstructures exhibit a structure-dependent elastic modulus which is subject to the tether length of straight-chain mercaptoalkyl acids or the ratio between silver and tether molecules. These superclusters are plastic and moldable against arbitrarily shaped masters of macroscopic dimensions, thereby opening a wealth of possibilities to develop more nanocrystals with practically useful nanoscopic properties. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Length of Acupuncture Training and Structural Plastic Brain Changes in Professional Acupuncturists

PubMed Central

Dong, Minghao; Zhao, Ling; Yuan, Kai; Zeng, Fang; Sun, Jinbo; Liu, Jixin; Yu, Dahua; von Deneen, Karen M.; Liang, Fanrong; Qin, Wei; Tian, Jie

2013-01-01

Background The research on brain plasticity has fascinated researchers for decades. Use/training serves as an instrumental factor to influence brain neuroplasticity. Parallel to acquisition of behavioral expertise, extensive use/training is concomitant with substantial changes of cortical structure. Acupuncturists, serving as a model par excellence to study tactile-motor and emotional regulation plasticity, receive intensive training in national medical schools following standardized training protocol. Moreover, their behavioral expertise is corroborated during long-term clinical practice. Although our previous study reported functional plastic brain changes in the acupuncturists, whether or not structural plastic changes occurred in acupuncturists is yet elusive. Methodology/Principal Findings Cohorts of acupuncturists (N = 22) and non-acupuncturists (N = 22) were recruited. Behavioral tests were delivered to assess the acupuncturists’ behavioral expertise. The results confirmed acupuncturists’ tactile-motor skills and emotion regulation proficiency compared to non-acupuncturists. Using the voxel-based morphometry technique, we revealed larger grey matter volumes in acupuncturists in the hand representation of the contralateral primary somatosensory cortex (SI), the right lobule V/VI and the bilateral ventral anterior cingulate cortex/ventral medial prefrontal cortex. Grey matter volumes of the SI and Lobule V/VI positively correlated with the duration of acupuncture practice. Conclusions To our best knowledge, this study provides first evidence for the anatomical alterations in acupuncturists, which would possibly be the neural correlates underlying acupuncturists’ exceptional skills. On one hand, we suggest our findings may have ramifications for tactile-motor rehabilitation. On the other hand, our results in emotion regulation domain may serve as a target for our future studies, from which we can understand how modulations of aversive emotions

Algorithms for elasto-plastic-creep postbuckling

NASA Technical Reports Server (NTRS)

Padovan, J.; Tovichakchaikul, S.

1984-01-01

This paper considers the development of an improved constrained time stepping scheme which can efficiently and stably handle the pre-post-buckling behavior of general structure subject to high temperature environments. Due to the generality of the scheme, the combined influence of elastic-plastic behavior can be handled in addition to time dependent creep effects. This includes structural problems exhibiting indefinite tangent properties. To illustrate the capability of the procedure, several benchmark problems employing finite element analyses are presented. These demonstrate the numerical efficiency and stability of the scheme. Additionally, the potential influence of complex creep histories on the buckling characteristics is considered.

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

PubMed Central

Bartsch, Julia C; Fidzinski, Pawel; Huck, Jojanneke HJ; Hörtnagl, Heide; Kovács, Richard; Liotta, Agustin; Priller, Josef; Wozny, Christian; Behr, Joachim

2015-01-01

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca2+ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system. PMID:25315194

Cell type dependence and variability in the short-term plasticity of EPSCs in identified mouse hippocampal interneurones

PubMed Central

Losonczy, Attila; Zhang, Limei; Shigemoto, Ryuichi; Somogyi, Peter; Nusser, Zoltan

2002-01-01

Synapses exhibit different short-term plasticity patterns and this behaviour influences information processing in neuronal networks. We tested how the short-term plasticity of excitatory postsynaptic currents (EPSCs) depends on the postsynaptic cell type, identified by axonal arborizations and molecular markers in the hippocampal CA1 area. Three distinct types of short-term synaptic behaviour (facilitating, depressing and combined facilitating–depressing) were defined by fitting a dynamic neurotransmission model to the data. Approximately 75 % of the oriens-lacunosum-moleculare (O-LM) interneurones received facilitating EPSCs, but in three of 12 O-LM cells EPSCs also showed significant depression. Over 90 % of the O-LM cells were immunopositive for somatostatin and mGluR1α and all tested cells were decorated by strongly mGluR7a positive axon terminals. Responses in eight of 12 basket cells were described well with a model involving only depression, but the other cells displayed combined facilitating–depressing EPSCs. No apparent difference was found between the plasticity of EPSCs in cholecystokinin- or parvalbumin-containing basket cells. In oriens-bistratified cells (O-Bi), two of nine cells showed facilitating EPSCs, another two depressing, and the remaining five cells combined facilitating–depressing EPSCs. Seven of 10 cells tested for somatostatin were immunopositive, but mGluR1α was detectable only in two of 11 tested cells. Furthermore, most O-Bi cells projected to the CA3 area and the subiculum, as well as outside the hippocampal formation. Postsynaptic responses to action potentials recorded in vivo from a CA1 place cell were modelled, and revealed great differences between and within cell types. Our results demonstrate that the short-term plasticity of EPSCs is cell type dependent, but with significant heterogeneity within all three interneurone populations. PMID:12096061

Internal state variable plasticity-damage modeling of AISI 4140 steel including microstructure-property relations: temperature and strain rate effects

NASA Astrophysics Data System (ADS)

Nacif el Alaoui, Reda

Mechanical structure-property relations have been quantified for AISI 4140 steel. under different strain rates and temperatures. The structure-property relations were used. to calibrate a microstructure-based internal state variable plasticity-damage model for. monotonic tension, compression and torsion plasticity, as well as damage evolution. Strong stress state and temperature dependences were observed for the AISI 4140 steel. Tension tests on three different notched Bridgman specimens were undertaken to study. the damage-triaxiality dependence for model validation purposes. Fracture surface. analysis was performed using Scanning Electron Microscopy (SEM) to quantify the void. nucleation and void sizes in the different specimens. The stress-strain behavior exhibited. a fairly large applied stress state (tension, compression dependence, and torsion), a. moderate temperature dependence, and a relatively small strain rate dependence.

Human Depotentiation following Induction of Spike Timing Dependent Plasticity.

PubMed

Pedroarena-Leal, Nicole; Heidemeyer, Larissa; Trenado, Carlos; Ruge, Diane

2018-06-18

Depotentiation (DP) is a crucial mechanism for the tuning of memory traces once LTP (Long Term Potentiation) has been induced via learning, artificial procedures, or other activities. Putative unuseful LTP might be abolished via this process. Its deficiency is thought to play a role in pathologies, such as drug induced dyskinesia. However, since it is thought that it represents a mechanism that is linked to the susceptibility to interference during consolidation of a memory trace, it is an important process to consider when therapeutic interventions, such as psychotherapy, are administered. Perhaps a person with an abnormal depotentiation is prone to lose learned effects very easily or on the other end of the spectrum is prone to overload with previously generated unuseful LTP. Perhaps this process partly explains why some disorders and patients are extremely resistant to therapy. The present study seeks to quantify the relationship between LTP and depotentiation in the human brain by using transcranial magnetic stimulation (TMS) over the cortex of healthy participants. The results provide further evidence that depotentiation can be quantified in humans by use of noninvasive brain stimulation techniques. They provide evidence that a nonfocal rhythmic on its own inefficient stimulation, such as a modified thetaburst stimulation, can depotentiate an associative, focal spike timing-dependent PAS (paired associative stimulation)-induced LTP. Therefore, the depotentiation-like process does not seem to be restricted to specific subgroups of synapses that have undergone LTP before. Most importantly, the induced LTP seems highly correlated with the amount of generated depotentiation in healthy individuals. This might be a phenomenon typical of health and might be distorted in brain pathologies, such as dystonia, or dyskinesias. The ratio of LTP/DP might be a valuable marker for potential distortions of persistence versus deletion of memory traces represented by LTP

Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan.

PubMed

Miyata, Shinji; Kitagawa, Hiroshi

2017-10-01

The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration. Here, we review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity, with a particular focus on the mechanism that regulates PV cell function through specific interactions between CS chains and their binding partners. We also discuss how the barrier function of the brain ECM restricts dendritic spine dynamics and limits axon regeneration after injury. The brain ECM not only forms physical barriers that modulate neural plasticity and axon regeneration, but also forms molecular brakes that actively controls maturation of PV cells and synapse plasticity in which sulfation patterns of CS chains play a key role. Structural remodeling of the brain ECM modulates neural function during development and pathogenesis. Genetic or enzymatic manipulation of the brain ECM may restore neural plasticity and enhance recovery from nerve injury. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. Copyright © 2017 Elsevier B.V. All rights reserved.

Electromigration-induced Plasticity and Texture in Cu Interconnects

NASA Astrophysics Data System (ADS)

Budiman, A. S.; Hau-Riege, C. S.; Besser, P. R.; Marathe, A.; Joo, Y.-C.; Tamura, N.; Patel, J. R.; Nix, W. D.

2007-10-01

Plastic deformation has been observed in damascene Cu interconnect test structures during an in-situ electromigration experiment and before the onset of visible microstructural damage (ie. voiding) using a synchrotron technique of white beam X-ray microdiffraction. We show here that the extent of this electromigration-induced plasticity is dependent on the texture of the Cu grains in the line. In lines with strong <111> textures, the extent of plastic deformation is found to be relatively large compared to our plasticity results in the previous study[1] using another set of Cu lines with weaker textures. This is consistent with our earlier observation that the occurrence of plastic deformation in a given grain can be strongly correlated with the availability of a <112> direction of the crystal in the proximity of the direction of the electron flow in the line (within an angle of 10°). In <111> out-of-plane oriented grains in a damascene interconnect scheme, the crystal plane facing the sidewall tends to be a {110} plane,[2-4] so as to minimize interfacial energy. Therefore, it is deterministic rather than probabilistic that the <111> grains will have a <112> direction nearly parallel to the direction of electron flow. Thus, strong <111> textures lead to more plasticity, as we observe.

CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

PubMed Central

Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

2016-01-01

Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV. DOI: http://dx.doi.org/10.7554/eLife.20985.001 PMID:27996938

A Re-Examination of Hebbian-Covariance Rules and Spike Timing-Dependent Plasticity in Cat Visual Cortex in vivo

PubMed Central

Frégnac, Yves; Pananceau, Marc; René, Alice; Huguet, Nazyed; Marre, Olivier; Levy, Manuel; Shulz, Daniel E.

2010-01-01

Spike timing-dependent plasticity (STDP) is considered as an ubiquitous rule for associative plasticity in cortical networks in vitro. However, limited supporting evidence for its functional role has been provided in vivo. In particular, there are very few studies demonstrating the co-occurrence of synaptic efficiency changes and alteration of sensory responses in adult cortex during Hebbian or STDP protocols. We addressed this issue by reviewing and comparing the functional effects of two types of cellular conditioning in cat visual cortex. The first one, referred to as the “covariance” protocol, obeys a generalized Hebbian framework, by imposing, for different stimuli, supervised positive and negative changes in covariance between postsynaptic and presynaptic activity rates. The second protocol, based on intracellular recordings, replicated in vivo variants of the theta-burst paradigm (TBS), proven successful in inducing long-term potentiation in vitro. Since it was shown to impose a precise correlation delay between the electrically activated thalamic input and the TBS-induced postsynaptic spike, this protocol can be seen as a probe of causal (“pre-before-post”) STDP. By choosing a thalamic region where the visual field representation was in retinotopic overlap with the intracellularly recorded cortical receptive field as the afferent site for supervised electrical stimulation, this protocol allowed to look for possible correlates between STDP and functional reorganization of the conditioned cortical receptive field. The rate-based “covariance protocol” induced significant and large amplitude changes in receptive field properties, in both kitten and adult V1 cortex. The TBS STDP-like protocol produced in the adult significant changes in the synaptic gain of the electrically activated thalamic pathway, but the statistical significance of the functional correlates was detectable mostly at the population level. Comparison of our observations with the

Sacrificial plastic mold with electroplatable base

DOEpatents

Domeier, Linda A.; Hruby, Jill M.; Morales, Alfredo M.

2002-01-01

A sacrificial plastic mold having an electroplatable backing is provided. One embodiment consists of the infusion of a softened or molten thermoplastic through a porous metal substrate (sheet, screen, mesh or foam) and into the features of a micro-scale molding tool contacting the porous metal substrate. Upon demolding, the porous metal substrate will be embedded within the thermoplastic and will project a plastic structure with features determined by the mold tool. This plastic structure, in turn, provides a sacrificial plastic mold mechanically bonded to the porous metal substrate which provides a conducting support suitable for electroplating either contiguous or non-contiguous metal replicates. After electroplating and lapping, the sacrificial plastic can be dissolved to leave the desired metal structure bonded to the porous metal substrate. Optionally, the electroplated structures may be debonded from the porous substrate by selective dissolution of the porous substrate or a coating thereon.

Castable plastic mold with electroplatable base

DOEpatents

Domeier, Linda A.; Morales, Alfredo M.; Gonzales, Marcela G.; Keifer, Patrick M.

2004-01-20

A sacrificial plastic mold having an electroplatable backing is provided as are methods of making such a mold via the infusion of a castable liquid formulation through a porous metal substrate (sheet, screen, mesh or foam) and into the features of a micro-scale master mold. Upon casting and demolding, the porous metal substrate is embedded within the cast formulation and projects a plastic structure with features determined by the mold tool. The plastic structure provides a sacrificial plastic mold mechanically bonded to the porous metal substrate, which provides a conducting support suitable for electroplating either contiguous or non-contiguous metal replicates. After electroplating and lapping, the sacrificial plastic can be dissolved, leaving the desired metal structure bonded to the porous metal substrate. Optionally, the electroplated structures may be debonded from the porous substrate by selective dissolution of the porous substrate or a coating thereon.

Sacrificial Plastic Mold With Electroplatable Base

DOEpatents

Domeier, Linda A.; Hruby, Jill M.; Morales, Alfredo M.

2005-08-16

A sacrificial plastic mold having an electroplatable backing is provided. One embodiment consists of the infusion of a softened or molten thermoplastic through a porous metal substrate (sheet, screen, mesh or foam) and into the features of a micro-scale molding tool contacting the porous metal substrate. Upon demolding, the porous metal substrate will be embedded within the thermoplastic and will project a plastic structure with features determined by the mold tool. This plastic structure, in turn, provides a sacrificial plastic mold mechanically bonded to the porous metal substrate which provides a conducting support suitable for electroplating either contiguous or non-contiguous metal replicates. After electroplating and lapping, the sacrificial plastic can be dissolved to leave the desired metal structure bonded to the porous metal substrate. Optionally, the electroplated structures may be debonded from the porous substrate by selective dissolution of the porous substrate or a coating thereon.

Analytical, Numerical and Experimental Examination of Reinforced Composites Beams Covered with Carbon Fiber Reinforced Plastic

NASA Astrophysics Data System (ADS)

Kasimzade, A. A.; Tuhta, S.

2012-03-01

In the article, analytical, numerical (Finite Element Method) and experimental investigation results of beam that was strengthened with fiber reinforced plastic-FRP composite has been given as comparative, the effect of FRP wrapping number to the maximum load and moment capacity has been evaluated depending on this results. Carbon FRP qualitative dependences have been occurred between wrapping number and beam load and moment capacity for repair-strengthen the reinforced concrete beams with carbon fiber. Shown possibilities of application traditional known analysis programs, for the analysis of Carbon Fiber Reinforced Plastic (CFRP) strengthened structures.

Shock temperature dependent rate law for plastic bonded explosives

NASA Astrophysics Data System (ADS)

Aslam, Tariq D.

2018-04-01

A reactive flow model for the tri-amino-tri-nitro-benzene (TATB) based plastic bonded explosive PBX 9502 (95% TATB, 5% polymeric binder Kel-F 800) is presented. This newly devised model is based primarily on the shock temperature of the material, along with local pressure, and accurately models a broader range of detonation and initiation scenarios. Specifically, sensitivity changes to the initial explosive temperature are accounted for naturally and with a single set of parameters. The equation of state forms for the reactants and products, as well as the thermodynamic closure of pressure and temperature equilibration, are carried over from the Wescott-Stewart-Davis (WSD) model [Wescott et al., J. Appl. Phys. 98, 053514 (2005) and "Modeling detonation diffraction and dead zones in PBX-9502," in Proceedings of the Thirteenth International Detonation Symposium (2006)]. This newly devised model, with Arrhenius state dependence on the shock temperature, based on the WSD equation of states, is denoted by AWSD. Modifying an existing implementation of the WSD model to the AWSD model in a hydrocode is a rather straightforward procedure.

MAGNETAR FIELD EVOLUTION AND CRUSTAL PLASTICITY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lander, S. K., E-mail: skl@soton.ac.uk

2016-06-20

The activity of magnetars is believed to be powered by colossal magnetic energy reservoirs. We sketch an evolutionary picture in which internal field evolution in magnetars generates a twisted corona, from which energy may be released suddenly in a single giant flare, or more gradually through smaller outbursts and persistent emission. Given the ages of magnetars and the energy of their giant flares, we suggest that their evolution is driven by a novel mechanism: magnetic flux transport/decay due to persistent plastic flow in the crust, which would invalidate the common assumption that the crustal lattice is static and evolves onlymore » under Hall drift and Ohmic decay. We estimate the field strength required to induce plastic flow as a function of crustal depth, and the viscosity of the plastic phase. The star’s superconducting core may also play a role in magnetar field evolution, depending on the star’s spindown history and how rotational vortices and magnetic fluxtubes interact.« less

Fundamental structure of steady plastic shock waves in metals

NASA Astrophysics Data System (ADS)

Molinari, A.; Ravichandran, G.

2004-02-01

The propagation of steady plane shock waves in metallic materials is considered. Following the constitutive framework adopted by R. J. Clifton [Shock Waves and the Mechanical Properties of Solids, edited by J. J. Burke and V. Weiss (Syracuse University Press, Syracuse, N.Y., 1971), p. 73] for analyzing elastic-plastic transient waves, an analytical solution of the steady state propagation of plastic shocks is proposed. The problem is formulated in a Lagrangian setting appropriate for large deformations. The material response is characterized by a quasistatic tensile (compression) test (providing the isothermal strain hardening law). In addition the elastic response is determined up to second order elastic constants by ultrasonic measurements. Based on this simple information, it is shown that the shock kinetics can be quite well described for moderate shocks in aluminum with stress amplitude up to 10 GPa. Under the later assumption, the elastic response is assumed to be isentropic, and thermomechanical coupling is neglected. The model material considered here is aluminum, but the analysis is general and can be applied to any viscoplastic material subjected to moderate amplitude shocks. Comparisons with experimental data are made for the shock velocity, the particle velocity and the shock structure. The shock structure is obtained by quadrature of a first order differential equation, which provides analytical results under certain simplifying assumptions. The effects of material parameters and loading conditions on the shock kinetics and shock structure are discussed. The shock width is characterized by assuming an overstress formulation for the viscoplastic response. The effects on the shock structure of strain rate sensitivity are analyzed and the rationale for the J. W. Swegle and D. E. Grady [J. Appl. Phys. 58, 692 (1985)] universal scaling law for homogeneous materials is explored. Finally, the ability to deduce information on the viscoplastic response of

Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

PubMed

Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

2018-03-07

Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

Experience-dependent mushroom body plasticity in butterflies: consequences of search complexity and host range

PubMed Central

Janz, Niklas; Schäpers, Alexander; Gamberale-Stille, Gabriella

2017-01-01

An ovipositing insect experiences many sensory challenges during her search for a suitable host plant. These sensory challenges become exceedingly pronounced when host range increases, as larger varieties of sensory inputs have to be perceived and processed in the brain. Neural capacities can be exceeded upon information overload, inflicting costs on oviposition accuracy. One presumed generalist strategy to diminish information overload is the acquisition of a focused search during its lifetime based on experiences within the current environment, a strategy opposed to a more genetically determined focus expected to be seen in relative specialists. We hypothesized that a broader host range is positively correlated with mushroom body (MB) plasticity, a brain structure related to learning and memory. To test this hypothesis, butterflies with diverging host ranges (Polygonia c-album, Aglais io and Aglais urticae) were subjected to differential environmental complexities for oviposition, after which ontogenetic MB calyx volume differences were compared among species. We found that the relative generalist species exhibited remarkable plasticity in ontogenetic MB volumes; MB growth was differentially stimulated based on the complexity of the experienced environment. For relative specialists, MB volume was more canalized. All in all, this study strongly suggests an impact of host range on brain plasticity in Nymphalid butterflies. PMID:29093221

Activity-Dependent Subcellular Cotrafficking of the Small GTPase Rem2 and Ca2+/CaM-Dependent Protein Kinase IIα

PubMed Central

Flynn, Robyn; Labrie-Dion, Etienne; Bernier, Nikolas; Colicos, Michael A.; De Koninck, Paul; Zamponi, Gerald W.

2012-01-01

Background Rem2 is a small monomeric GTP-binding protein of the RGK family, whose known functions are modulation of calcium channel currents and alterations of cytoskeletal architecture. Rem2 is the only RGK protein found predominantly in the brain, where it has been linked to synaptic development. We wished to determine the effect of neuronal activity on the subcellular distribution of Rem2 and its interacting partners. Results We show that Rem2 undergoes activity-and N-Methyl-D-Aspartate Receptor (NMDAR)-dependent translocation in rat hippocampal neurons. This redistribution of Rem2, from a diffuse pattern to one that is highly punctate, is dependent on Ca2+ influx, on binding to calmodulin (CaM), and also involves an auto-inhibitory domain within the Rem2 distal C-terminus region. We found that Rem2 can bind to Ca2+/CaM-dependent protein kinase IIα (CaMKII) a in Ca2+/CaM-dependent manner. Furthermore, our data reveal a spatial and temporal correlation between NMDAR-dependent clustering of Rem2 and CaMKII in neurons, indicating co-assembly and co-trafficking in neurons. Finally, we show that inhibiting CaMKII aggregation in neurons and HEK cells reduces Rem2 clustering, and that Rem2 affects the baseline distribution of CaMKII in HEK cells. Conclusions Our data suggest a novel function for Rem2 in co-trafficking with CaMKII, and thus potentially expose a role in neuronal plasticity. PMID:22815963

A neuromorphic implementation of multiple spike-timing synaptic plasticity rules for large-scale neural networks

PubMed Central

Wang, Runchun M.; Hamilton, Tara J.; Tapson, Jonathan C.; van Schaik, André

2015-01-01

We present a neuromorphic implementation of multiple synaptic plasticity learning rules, which include both Spike Timing Dependent Plasticity (STDP) and Spike Timing Dependent Delay Plasticity (STDDP). We present a fully digital implementation as well as a mixed-signal implementation, both of which use a novel dynamic-assignment time-multiplexing approach and support up to 226 (64M) synaptic plasticity elements. Rather than implementing dedicated synapses for particular types of synaptic plasticity, we implemented a more generic synaptic plasticity adaptor array that is separate from the neurons in the neural network. Each adaptor performs synaptic plasticity according to the arrival times of the pre- and post-synaptic spikes assigned to it, and sends out a weighted or delayed pre-synaptic spike to the post-synaptic neuron in the neural network. This strategy provides great flexibility for building complex large-scale neural networks, as a neural network can be configured for multiple synaptic plasticity rules without changing its structure. We validate the proposed neuromorphic implementations with measurement results and illustrate that the circuits are capable of performing both STDP and STDDP. We argue that it is practical to scale the work presented here up to 236 (64G) synaptic adaptors on a current high-end FPGA platform. PMID:26041985

THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

PubMed

Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

2018-03-01