Spike-timing dependent plasticity is a learning mechanism used extensively within neural modelling. The learning rule has been shown to allow a neuron to find the onset of a spatio-temporal pattern repeated among its afferents. In this thesis, the first question addressed is what does this neuron learn? With a spiking neuron model and linear prediction, evidence is adduced that the neuron learns two components: (1) the level of average background activity and (2) specific spike times of a pattern. Taking advantage of these findings, a network is developed that can train recognisers for longer spatio-temporal input signals using spike-timing dependent plasticity. Using a number of neurons that are mutually connected by plastic synapses and subject to a global winner-takes-all mechanism, chains of neurons can form where each neuron is selective to a different segment of a repeating input pattern, and the neurons are feedforwardly connected in such a way that both the correct stimulus and the ...
Supervisors: Ole Paulsen, Tanja Fuchsberger. Spike timing-dependent plasticity (STDP) is a physiologically relevant form of Hebbian learning, in which near coincident pre- and postsynaptic firing induces synaptic plasticity: Long term potentiation (LTP) is induced when the presynaptic spike precedes postsynaptic firing, and long term depression (LTD) when postsynaptic firing precedes the presynaptic spike [1]. However, these plasticity rules are profoundly influenced by neuromodulators [2]. Reward, novelty or surprise are correlated with neuromodulatory signals, such as dopamine, acetylcholine or noradrenaline, which modulate memories and behavioural outcome. They regulate STDP through various mechanisms, as they can control the biophysical properties of dendrites, including the dynamics of spike backpropagation, and can influence the state of kinases and phosphatases implicated in synaptic plasticity (Seol et al., 2007). In our laboratory we recently demonstrated a retroactive effect of ...
Long-term potentiation (LTP) and long-term depression (LTD) are generally assumed to be cellular correlates for learning and memory. Different types of LTP induction protocols differing in severity of stimulation can be distinguished in CA1 of the hippocampus. To better understand signaling mechanisms and involvement of neuromodulators such as dopamine in synaptic plasticity, less severe and more physiological low frequency induction protocols should be used. In the study which is reviewed here, critical determinants of spike timing-dependent plasticity (STDP) at hippocampal CA3-CA1 synapses were investigated. We found that dopamine via D1 receptor signaling, but not adrenergic signaling activated by the -adrenergic agonist isoproterenol, is important for successful expression of STDP at CA3-CA1 synapses. The dopamine effect on STDP is paralleled by changes in spike firing properties, thereby changing intrinsic excitability of postsynaptic CA1 neurons, and gating STDP,. Whereas β-adrenergic
Structure-based virtual screening for selecting potential drug candidates is usually challenged by how numerous false positives in a molecule library are excluded when receptor plasticity is considered. In this study, based on the binding energy landscape theory, a hypothesis that a true inhibitor can bind to different conformations of the binding site favorably was put forth, and related strategies to defeat this challenge were devised; reducing false positives when receptor plasticity is considered. The receptor in the study is the influenza A nucleoprotein, whose oligomerization is a requirement for RNA binding. The structural flexibility of influenza A nucleoprotein was explored by molecular dynamics simulations. The resultant distinctive structures and the crystal structure were used as receptor models in docking exercises in which two binding sites, the tail-loop binding pocket and the RNA binding site, were targeted with the Otava PrimScreen1 diversity-molecule library using the GOLD software.
Synaptic plasticity directs development of the nervous system and is thought to underlie memory storage in adult animals. A great deal of our current understanding of the role of AMPA receptors in synaptic plasticity comes from studies on developing cortex and cell cultures. In the present study, we instead focus on plasticity in mature neurons in the neocortex of adult animals. We find that the glutamate receptor 1 (GluR1) subunit of the AMPA receptor is involved in experience-dependent plasticity in adult cortex in vivo and that it acts in addition to neuronal nitric oxide synthase (αNOS1), an enzyme that produces the rapid synaptic signaling molecule nitric oxide (NO). Potentiation of the spared whisker response, following single whisker experience, is ∼33% less in GluR1-null mutants than in wild types. We found that the remaining plasticity depended on αNOS1. Potentiation was reduced by ,42% in the single αNOS1-null mutants and completely abolished in GluR1/αNOS1 double-knock-out mice. ...
Background. Synaptic plasticity is thought to be the cellular correlate for the formation of memory traces in the brain. Recently, spike-timing dependent plasticity has gained increased interest as a plausible physiological mechanism for the activity-dependent modification of synaptic strength. It might be fundamental for circuit refinement, map plasticity and the explanation of higher brain functions. It is not clear if spike-timing dependent plasticity is a universal learning rule based on simple biophysical mechanisms. The molecular signalling pathways involved are quite diverse and apparently use-dependent. The fundamental question is what determines the molecular machinery at a synaptic contact that translates electrical activity into a change in synaptic strength.Specific Aims. (1) The influence of active dendritic properties, which can result in the generation of local dendritic spikes, on changes in synaptic strength will be studied. They will have an important impact on the local ...
The plasticity of inhibitory transmission is expected to play a key role in the modulation of neuronal excitability and network function. Over the last two decades, the investigation of the determinants of inhibitory synaptic plasticity has allowed distinguishing presynaptic and postsynaptic mechanisms. While there has been a remarkable progress in the characterization of presynaptically-expressed plasticity of inhibition, the postsynaptic mechanisms of inhibitory long-term synaptic plasticity only begin to be unraveled. At postsynaptic level, the expression of inhibitory synaptic plasticity involves the rearrangement of the postsynaptic molecular components of the GABAergic synapse, including GABAA receptors, scaffold proteins and structural molecules. This implies a dynamic modulation of receptor intracellular trafficking and receptor surface lateral diffusion, along with regulation of the availability and distribution of scaffold proteins. This Review will focus on the mechanisms of the multifaceted
Neuroplasticity studies examining children with hemiparesis (CH) have focused predominantly on unilateral interventions. CH also have bimanual coordination impairments with bimanual interventions showing benefits. We explored neuroplasticity following hand-Arm bimanual intensive therapy (HABIT) of 60 hours in twelve CH (6 females, mean age 11 ± 3.6 y). Serial behavioral evaluations and MR imaging including diffusion tensor (DTI) and functional (fMRI) imaging were performed before, immediately after, and at 6-week follow-up. Manual skills were assessed repeatedly with the Assisting Hand Assessment, Childrens Hand Experience Questionnaire, and Jebsen-Taylor Test of Hand Function. Beta values, indicating the level of activation, and lateralization index (LI), indicating the pattern of brain activation, were computed from fMRI. White matter integrity of major fibers was assessed using DTI. 11/12 children showed improvement after intervention in at least one measure, with 8/12 improving on two or ...
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Bacterial morphological plasticity refers to changes in the shape and size that bacterial cells undergo when they encounter stressful environments. Although bacteria have evolved complex molecular strategies to maintain their shape, many are able to alter their shape as a survival strategy in response to protist predators, antibiotics, the immune response, and other threats. Normally, bacteria have different shapes and sizes which include coccus, rod and helical/spiral (among others less common) and that allow for their classification. For instance, rod shapes may allow bacteria to attach more readily in environments with shear stress (e.g., in flowing water). Cocci may have access to small pores, creating more attachment sites per cell and hiding themselves from external shear forces. Spiral bacteria combine some of the characteristics cocci (small footprints) and of filaments (more surface area on which shear forces can act) and the ability to form an unbroken set of cells to build biofilms. ...
The ability to generate action potentials (spikes) in response to synaptic input determines whether a neuron participates in information processing. How a developing neuron becomes an active participant in a circuit or whether this process is activity dependent is not known, especially as spike-dependent plasticity mechanisms would not be available to non-spiking neurons. Here we use the optic tectum of awake Xenopus laevis tadpoles to determine how a neuron becomes able to generate sensory-driven spikes in vivo. At the onset of vision, many tectal neurons do not exhibit visual spiking behavior, despite being intrinsically excitable and receiving visuotopically organized synaptic inputs. However, a brief period of visual stimulation can drive these neurons to start generating stimulus-driven spikes. This conversion relies upon a selective increase in glutamatergic input and requires depolarizing GABAergic transmission and NMDA receptor activation. This permissive form of experience-dependent plasticity
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Our overarching interest is in the question of how experience and deprivation modify synaptic connections in the brain. Experience-dependent synaptic plasticity is the physical substrate of memory, sculpts connections during postnatal development to determine the capabilities and limitations of brain functions, is responsible for the reorganization of the brain after damage, and is vulnerable in numerous psychiatric and neurological diseases and contributes to their symptoms.. Historically, our major efforts to address this question have been focused on the visual cortex and hippocampus. The visual cortex is a site of robust experience-dependent synaptic plasticity, exemplified by the consequences of temporary monocular deprivation (MD) during childhood. MD sets in motion a stereotyped choreography of synaptic modification whereby the deprived-eye inputs to visual cortex rapidly lose strength and, with a delay, the open-eye inputs undergo a compensatory gain in strength. The behavioral ...
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AD patients show after iTBS an impairment of LTP-like cortical plasticity forming a paradoxical LTD in comparison to HS. LTD-like cortical plasticity is similar between AD and HS. LTP-like cortical plasticity is not associated with age, but AD patients presenting with more altered LTP-like cortical plasticity have more-severe cognitive decline at 18 months. SAI is impaired in AD and shows a strong association with the individual age of subjects rather than with disease age of onset.. ...
A major hallmark of brain diseases is neuroinflammation. We are interested in how immune mediators affect synaptic plasticity. Particularly, our work focuses on better understanding how these factors influence intracellular calcium stores, i.e. the spine apparatus organelle, and how these changes alter the ability of neurons to express associative and homeostatic synaptic plasticity. We study the role of coagulation factors in this context and test whether these changes can be modified by rTMS.. Ben Shimon M*, Lenz M*, Ikenberg B, Becker D, Shavit Stein E, Chapmann J, Tanne D, Pick CG, Blatt I, Neufeld M, Vlachos A*, Maggio N*° (2015) Thrombin regulation of synaptic transmission and plasticity: implications for health and disease. Front Cel Neurosci. 9: 151.. Becker D, Deller T, Vlachos A° (2015) Tumor necrosis factor (TNF)-receptor 1 and 2 mediate homeostatic synaptic plasticity of denervated mouse dentate granule cells. Sci Rep. 5: 12726.. Strehl A, Lenz M, Itsekson-Hayosh Z, Becker D, ...
The role of dopamine in plasticity at glutamatergic synapses in the striatum is central to our understanding of basal ganglia functions and dopamine-dependent reward mechanisms. Long-term potentiation (LTP) and long-term depression (LTD) at these synapses are thought to be dependent on D1 and D2 dopamine receptors, respectively. However, the mechanisms of LTP and LTD in the striatum are controversial. Using brain slices from transgenic mice, Shen et al. show that LTP and LTD can occur in both D1- and D2-expressing neurons but with different molecular mechanisms. Dopaminergic modulation of plasticity is receptor and cell-type specific. The findings suggest that the control of bidirectional plasticity is not exerted through a monolithic mechanism, as previously asserted, but by cell-type-specific mechanisms depending on the subtype of dopamine receptor expressed.. W. Shen, M. Flajolet, P. Greengard, D. J. Surmeier, Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321, ...
The Haas Lab has developed specific visual stimulation protocols consisted of different periods of light ON and OFF stimuli to induce plasticity or metaplasticity in the optic tectum of awake Xenopus laevis tadpoles (Dunfield and Haas, 2009, 2010; Chen et al. 2012). Using these experience-driven neuronal plasticity induction stimuli and two-photon time-lapse imaging of mitochondrial movement and dendritic arbor growth, and calcium imaging of neuronal activity of individual neurons in the intact and awake developing brain, we are looking at mitochondria localization and size in LTD and LTP neurons. Other imaging and molecular techniques are also being used to underline the specific mitochondria proteins that regulate synaptic plasticity. ...
Synaptic Plasticity. Synaptic Plasticity. I. Synaptic Plasticity (Excitatory spine synapses) Changes in synaptic strength are important for formation of memory. Short Term Plasticity (paired-pulse facilitation, short-term potentiation, synaptic depression) Slideshow 6690266 by lev-levine
Challenges in the pain field include translation from animal models to identification of novel targets for drug development for humans and developing strategies that lead to improvements in patient care. Toward this goal, the symposium featured presentations that reviewed advances in the basic science and clinical arenas. Timothy Brennan, Ph.D., M.D. (Associate Professor of Anesthesia and Pharmacology, University of Iowa, Iowa City, Iowa), discussed the "Peripheral and Central Plasticity in an Animal Model of Incisional Pain" and Gary Strichartz, Ph.D. (Professor of Anesthesia, Pharmacology and Biophysics, Harvard Medical School, Brigham and Womens Hospital, Boston, Massachusetts), reviewed "Pharmacological Studies on Preventing or Modulating the Plastic Changes in Experimental Models of Incisional Pain." Additional presentations on "Clinical Evidence for Neural Plasticity in the Postoperative Period: Its Relevance and Modulation" and "Persistent Pain following Surgery: Neurobiological ...
The efficacy of synaptic transmission changes depending on the neuronal activity in the central nervous system. Such synaptic plasticity underlies experience-dependent refinement of information proces
Learning is primarily mediated by activity-dependent modifications of synaptic strength within neuronal circuits. We discovered that place fields in hippocampal area CA1 are produced by a synaptic potentiation notably different from Hebbian plasticity. Place fields could be produced in vivo in a single trial by potentiation of input that arrived seconds before and after complex spiking. The potentiated synaptic input was not initially coincident with action potentials or depolarization. This rule, named behavioral time scale synaptic plasticity, abruptly modifies inputs that were neither causal nor close in time to postsynaptic activation. In slices, five pairings of subthreshold presynaptic activity and calcium (Ca(2+)) plateau potentials produced a large potentiation with an asymmetric seconds-long time course. This plasticity efficiently stores entire behavioral sequences within synaptic weights to produce predictive place cell activity.. ...
Spike timing-dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst inductio
Arm-amputation involves two powerful drivers for brain plasticity-sensory deprivation and altered use. However, research has largely focused on sensory deprivation and maladaptive change. Here we show that adaptive patterns of limb usage after amputation drive cortical plasticity. We report that individuals with congenital or acquired limb-absence vary in whether they preferentially use their intact hand or residual arm in daily activities. Using fMRI, we show that the deprived sensorimotor cortex is employed by whichever limb individuals are over-using. Individuals from either group that rely more on their intact hands (and report less frequent residual arm usage) showed increased intact hand representation in the deprived cortex, and increased white matter fractional anisotropy underlying the deprived cortex, irrespective of the age at which deprivation occurred. Our results demonstrate how experience-driven plasticity in the human brain can transcend boundaries that have been thought to limit
Citation: Freire, R., Cheng, H. 2004. Experience-dependent changes in the hippocampus of domestic chicks: a model for spatial memory. European Journal of Neuroscience. 20(4):1065-1068. Interpretive Summary: In the modern broiler industry, chickens housed in large groups do not space themselves evenly but instead crowd in particular areas, which may affect chicken health and increase mortality. One contributing factor may be a deficit in spatial skills arising from the absence of essential environmental factors during routine rearing. The present study was to examine whether chick spatial skills can be improved by experimental training at an early age. Compared to control chicks, experience-induced changes in brain morphology reported here suggest that early experience leads to changes in the hippocampus that appear to be related to the development of spatial memory. Enhanced spatial memory in chickens may result in improving their well-being by increasing their distribution and their skills to ...
... , Yi Zhang, Rui Ma, Shaohong Zou, Gaiyu Tong, Gulibakeranmu Abula, Manna
The long-term goal of our research is to understand the neural circuit basis of learning and memory. In this project, we aim to understand how neural circuits p...
In D2 MSNs (fig. S1), repeated pairing of a synaptic stimulation with a postsynaptic spike 5 ms later resulted in LTP of the synaptic response (Fig. 1D). In contrast, preceding synaptic stimulation (-10 ms) with a short burst of postsynaptic spikes induced LTD (Fig. 1E). There were no lasting alterations in synaptic strength with unpaired presynaptic or postsynaptic activity (fig. S1).. Previous studies of striatal LTD induced by conventional plasticity protocols have underscored the importance of D2 receptors (7, 8, 16). In D2 MSNs, timing-dependent LTD was disrupted by antagonizing D2 receptors with sulpiride (control n = 5; sulpiride n = 5; P , 0.05, Mann-Whitney rank sum test), suggesting a similar involvement of D2 receptors (Fig. 1F). Moreover, LTD was disrupted by antagonizing CB1 endocannabinoid (fig. S2) or mGluR5 glutamate receptors (fig. S3). The combination of presynaptic activity and activation of terminal CB1 receptors leads to a lasting reduction in glutamate release probability ...
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The molecular mechanisms controlling the delivery and subsequent stabilization of AMPARs during synaptic plasticity are still poorly understood. Recent findings have suggested PSD-95 as candidate molecule in these processes (El-Husseini et al., 2000; Schnell et al., 2002; Beique, 2003). However, particularly in the light of findings from PSD-95 mutant mice that exhibit enhanced LTP (Migaud et al., 1998), it remained controversial whether and how PSD-95 participates in synaptic plasticity. Here, we show that PSD-95 controls AMPAR delivery during synaptic strengthening by LTP in vitro and during experience-driven synaptic plasticity in vivo. We use three criteria to establish this: First, expression of wt PSD-95 mimics, and second wt PSD-95 occludes AMPAR delivery during synaptic strengthening; third, dominant negative forms of PSD-95 block the incorporation of AMPAR during plasticity.. Several findings indicate that expression of PSD-95 mimics key aspects of LTP and experience-driven synaptic ...
Network structure determines the flow of electrical activity in every neural network and determines its functional and computational properties. Electrical activation of the neuron goes along with an intracellular increase in calcium which induces morphological alterations of the neuron on a slower time scale. Morphological changes, such as changes in dendritic spine and axonal bouton numbers as well as elongation, retraction and branching of axons and dendrites have direct impact on network connectivity (structural plasticity) even in the adult brain: As a consequence of morphological changes, synapses may break, new synapses can form and axonal branches can be re-routed. Rewired network connectivity, in turn, gives rise to an altered activity dynamic and may hold as a source for long term memory formation. Experimental data further support the notion that structural plasticity is not necessarily Hebbian-like but may serve as a neuronal mechanism to maintain electrical activity at a certain ...
When a cell has to endure lasting changes in its environment that require it to actively transport more molecules than normal through the cell membra...
The long-term goal of this project is to identify thalamocortical network mechanisms involved in consolidating experience-dependent plasticity in the visual sys...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The induction of both LTP and LTD was equally sensitive to loading of the postsynaptic cell with the rapidly equilibrating Ca2+ buffer BAPTA or the slower buffer EGTA. Therefore, the volume-averaged elevation of spine [Ca2+]i is an important factor for the induction of changes in synaptic strength. The putative Ca2+ sensors that trigger the induction of LTP or LTD presumably are separated from the Ca2+ entry site by several tens of nanometers (Neher, 1998). They might be mobile Ca2+ buffers, which compete with Ca2+ extrusion and additional fixed Ca2+ buffers. Another possibility is that the Ca2+ sensors have slower binding kinetics for Ca2+ than EGTA. In this case the Ca2+ sensors might be localized in close proximity to Ca2+ channels, but still they would be sensitive mainly to the volume-averaged increases in [Ca2+]i. In the case of LTP, calmodulin is a possible candidate Ca2+ sensor. It can activate Ca2+/calmodulin-dependent protein kinase II (CaMKII), which translocates to the plasma ...
Brain plasticity is profoundly impacted by ones living environment. The hippocampus, involved in learning and memory, is highly susceptible to plasticity. Raising rodents in an
In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory evoked activity. Importantly, inhibitory transmission is highly plastic, but the functional role of inhibitory synaptic plasticity is unknown. In the mouse barrel cortex, activation of layer (L) 2/3 pyramidal neurons (PNs) elicits strong feedforward inhibition (FFI) onto L5 PNs. We find that FFI involving parvalbumin (PV)-expressing cells is strongly potentiated by postsynaptic PN burst firing. FFI plasticity modifies the PN excitation-to-inhibition (E/I) ratio, strongly modulates PN gain, and alters information transfer across cortical layers. Moreover, our LTPi-inducing protocol modifies firing of L5 PNs and alters the temporal association of PN spikes to γ-oscillations both in vitro and in vivo. All of these effects are captured by unbalancing the E/I ratio in a feedforward inhibition circuit model. Altogether, our results indicate that activity-dependent modulation of perisomatic inhibitory strength ...
Exercise is beneficial to the brain, as it increases brain plasticity. Our brains neurons can keep changing with experience, learning and memory through a process called brain plasticity.
Memory is a highly complex cognitive function that involves interactions between numerous brain structures, proteins and signalling molecules. Indeed, experience-dependent changes in the strength of synaptic connections between neurons are thought to underlie information storage in the brain. Thus, understanding the highly elastic nature - or the plasticity - of synapses is critical to uncovering how the brain converts our individual experiences into lasting memories. To this end, modulatory neurotransmitter systems play a central role in shaping synaptic processes involved in the encoding and retention of information within neural circuits. A fundamental problem remains, though, in understanding how extrinsic factors recruit, mimic or even hijack these endogenous regulatory signals to affect the development of brain systems critical to cognitive and mnemonic function. The primary focus of my research is in determining how the hippocampus and parahippocampal cortices integrate signals from ...
The Jay Baraban Laboratory studies key aspects of neuronal plasticity induced by environmental stimuli, including drugs. The ability of the microRNA system to regulate protein translation in the vicinity of synapses indicates it is well positioned to play a central role in regulating synaptic plasticity. Accordingly, we are studying how this system regulates synaptic function. In particular, we have identified the translin/trax RNAse complex as a key regulator of microRNA processing and are using genetically engineered mice that lack this complex to understand its role in neuronal function. For example, these mice display defects in responsiveness to cocaine and in certain forms of synaptic plasticity. We use a combination of behavioral and molecular approaches to conduct studies aimed at understanding how the microRNA system regulates these processes.. Research Areas: synaptic plasticity, neuronal plasticity, drugs, RNA ...
The team is working on changes in the neurobiological substrate during learning and memory processes, including in pathological conditions. The underlying hypothesis is that durable memory traces proceed from the marking of specific neural networks. These synaptic plasticity mechanisms result from molecular and structural changes that largely remain to be identified and integrated at the behavioral level.. In mice, we developed a new olfactory test, "the tubular olfactory maze" where we test the effect of molecules or genetic manipulations on different memory subcategories. We observed specific structural changes in the dorsal and apical dendrite density of CA1 pyramidal cells of the hippocampus, specifically amplified by a 5-HT4 receptor agonist known for his promnesic effect. We are currently using this test in a model of Alzheimers disease (5XFAD transgenic mice).. With the same aim of creating animal models to study memory, we developed a deferred task paradigm in mice that highlights ...
NEURON mod files from the paper: M. Migliore, et al. (2015). In this paper, we investigate the possibility that the experimental protocols on synaptic plasticity may result in different consequences (e.g., LTD instead of LTP), according to the initial conditions of the stimulated synapses, and can generate confusing results. Using biophysical models of synaptic plasticity and hippocampal CA1 pyramidal neurons, we study how, why, and to what extent EPSPs observed at the soma after induction of LTP/LTD reflects the actual (local) synaptic state. The model and the results suggest a physiologically plausible explanation of why LTD induction is experimentally difficult, and they offer experimentally testable predictions on the stimulation protocols that may be more effective ...
20) Spike-timing dependent plasticity: Getting the brain from correlation to causation (Levy - 1983, Sakmann - 1994, Bi & Poo - 1998, Dan - 2002). Hebbs original proposal was worded as such: When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that As efficiency, as one of the cells firing B, is increased. [emphasis added]. The phrase takes part in firing implies causation of Bs activity via As activity, not simply a correlation of the two.. There are several ways to go beyond correlation to infer causation. One method is to observe that one event (e.g., cell As activity) comes just before the caused event (e.g., cell Bs activity).. In 1983 Levy showed with hippocampal slices that electrically stimulating cell A to fire before cell B will cause long-lasting strengthening of the synapse from cell A to cell B. However, when the opposite occurs, and ...
Connect and collaborate with Trevor Bekolay, with research interests in Long-term memory and Spike-timing dependent plasticity, on Mendeley.
SYMPTOMS AND SIGNS CAUSED BY NEURAL PLASTICITY. Signs and symptoms of disorders. Not everything can be seen on MRI or other imaging techniques Not everything has positive laboratory tests. Neural plasticity play greater role in generating symptoms and signs than previously assumed. Slideshow 3772149 by fordon
Phenotypic plasticity, the ability of cells to reversibly alter their phenotypes in response to signals, presents a significant clinical challenge to treating solid tumors. Tumor cells utilize phenotypic plasticity to evade therapies, metastasize, and colonize distant organs. As a result, phenotypic plasticity can accelerate tumor progression. A well-studied example of phenotypic plasticity is the bidirectional conversions among epithelial, mesenchymal, and hybrid epithelial/mesenchymal (E/M) phenotype(s). These conversions can alter a repertoire of cellular traits associated with multiple hallmarks of cancer, such as metabolism, immune evasion, invasion, and metastasis. To tackle the complexity and heterogeneity of these transitions, mathematical models have been developed that seek to capture the experimentally verified molecular mechanisms and act as hypothesis-generating machines. Here, we discuss how these quantitative mathematical models have helped us explain existing experimental data, ...
The main research interest of Dr. Thiels is how animals acquire information from the environment and use that information to guide their behavior. Understanding of the biological substrates of learning and memory is one of the most sought-after goals of neuroscience because of the universality of these cognitive faculties and their utmost importance for survival in a variable environment. Growing evidence indicates that learning and memory involve specific neural circuits and, within these circuits, specific physiological, biochemical, and molecular processes. Likely neurophysiological substrates of learning and memory include experience-induced changes in the strength of synaptic communication. Dr. Thiels laboratory studies experience-dependent bidirectional synaptic plasticity in the hippocampus, a structure in the medial temporal lobes critical for the acquisition and storage of episodic and factual memories. Another, recently initiated line of study in the laboratory focuses on ...
J. Liepert, W. H. R. Miltner, H. Bauder, M. Sommer, C. Dettmers, E. Taub, and C. Weiller. 1998. Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neuroscience Letter, 250: pp. 5-8 ...
How do human infants learn the causal dependencies between events? Evidence suggests that this remarkable feat can be achieved by observation of only a handful of examples. Many computational models have been produced to explain how infants perform causal inference without explicit teaching about statistics or the scientific method. Here, we propose a spiking neuronal network implementation that can be entrained to form a dynamical model of the temporal and causal relationships between events that it observes. The network uses spike-time dependent plasticity, long-term depression, and heterosynaptic competition rules to implement Rescorla-Wagner-like learning. Transmission delays between neurons allow the network to learn a forward model of the temporal relationships between events. Within this framework, biologically realistic synaptic plasticity rules account for well-known behavioral data regarding cognitive causal assumptions such as backwards blocking and screening-off. These models can ...
Semantic Scholar extracted view of Steroids in the brain: regulators of brain plasticity and protectors against neuronal damage. by Cordian Beyer et al.
How do human infants learn the causal dependencies between events? Evidence suggests that this remarkable feat can be achieved by observation of only a handful of examples. Many computational models have been produced to explain how infants perform causal inference without explicit teaching about statistics or the scientific method. Here, we propose a spiking neuronal network implementation that can be entrained to form a dynamical model of the temporal and causal relationships between events that it observes. The network uses spike-time dependent plasticity, long-term depression, and heterosynaptic competition rules to implement Rescorla-Wagner-like learning. Transmission delays between neurons allow the network to learn a forward model of the temporal relationships between events. Within this framework, biologically realistic synaptic plasticity rules account for well-known behavioral data regarding cognitive causal assumptions such as backwards blocking and screening-off. These models can ...
The product of this gene belongs to the Serine/Threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This enzyme is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Two transcript variants encoding distinct isoforms have been identified for this gene ...
article{c4f10640-1893-48bd-8bbf-fd04ad0d7a94, author = {Johansson, Barbro}, issn = {0022-9717}, language = {eng}, number = {4}, pages = {46--231}, publisher = {Keio Gijuku Daigaku Igakubu}, series = {The Keio journal of medicine}, title = {Brain plasticity in health and disease.}, volume = {53}, year = {2004 ...
Regulation of myelination by neural impulse activity Synaptic plasticity Hippocampal synaptic plasticity Regulation of gene expression by action-potential firing patterns
Input-dependent synaptic plasticity is critical for the reproducible activation of a specific neuronal assembly encoding a particular memory. The synaptic tagging hypothesis, which suggests how input specificity is maintained in late-phase synaptic plasticity, attempts to explain the persistence of long-term memory. However, it has been difficult to identify proteins that behave as the hypothesis predicts. Okada et al. investigated whether the regulated spine entry of a late-phase-related somatically synthesized plasticity-related protein, Vesl-1S, works as a synaptic tag. Vesl-1S protein was carried from the soma to every dendrite and recruited into spines by synaptic activation in an input-specific manner. Spine entry was protein-synthesis independent, was NMDA-receptor dependent, and had a persistent lifetime of activation. These results provide long-sought evidence for the input-specific capturing of a plasticity-related protein as postulated by the synaptic tagging hypothesis.. D. Okada, F. ...
Brain plasticity, or neuroplasticity, can be defined at the capability of the nervous system to change. Learn everything you need to know about neuroplasticity and how exercising it with CogniFit can boost your skills to recover and restructure themselves.
The inherent flexibility of the immune system is even more complex than previously thought, as thats the basis of vaccine-mediated immunity.
www.MOLUNA.de Synaptic Plasticity and Transsynaptic Signaling [4174086] - Brain functions are realized by the activity of neuronal networks composed of a huge number of neurons. The efficiency of information transfer within the networks is changeable. Even the networks themselves can change through experience. Information transfer between neurons is performed at the synapse (the site of the neurons contact)
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Integrated Brain Restoration after Ischemic Stroke -- Medical Management, Risk Factors, Nutrients, and other Interventions for Managing Inflammation and Enhancing Brain Plasticity. Brain injury from ischemic stroke can be devastating, but full brain restoration is feasible. Time until treatment is critical; rapid rate of injury progression, logistical and personnel constrai.... ...
University of Bristol - person profile - MRC Centre for Synaptic Plasticity - Professor Stafford Lightman - Regulation of the hypothalamo-pituitary-adrenal (HPA) axis in health and disease.
Ottawa: Looking at the effects of hormone therapy on females, researchers have found that pregnancy and motherhood could stimulate certain permanent changes in the brain. Hormone therapy is prescribed to alleviate some of the symptoms of menopause
By examining the ways in which were trying to fool ourselves into thinking our condition can be lived with, we might just jump ahead a couple of steps and move onto some real -- and surprisingly simple -- changes that can have a lasting effect on not only our overall health, but also our psyche.
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The model hereby clarifies, for the first time, how the following levels of brain organization coexist to realize cognitive processing properties that regulate fast learning and stable memory of brain representations: single cell properties, such as spiking dynamics, spike-timing-dependent plasticity (STDP), and acetylcholine modulation; detailed laminar thalamic and cortical circuit designs and their interactions; aggregate cell recordings, such as current-source densities and local field potentials; and single cell and large-scale inter-areal oscillations in the gamma and beta frequency domains ...
Biundo F, dAbramo C, Tambini MD, Zhang H, Del Prete D, Vitale F, Giliberto L, Arancio O, DAdamio L. Abolishing Tau cleavage by caspases at Aspartate421 causes memory/synaptic plasticity deficits and pre-pathological Tau alterations ...
Below is something I have actually found that might be of interest. Theres a great deal said on this topic, nonetheless attempting to get to the bottom of things has actually taken me a while. This is just one of the posts I discovered. If its not to your taste Ive put some links at…
Neuroplasticity: The brains ability to reorganize itself by forming new neural connections throughout life. Neuroplasticity allows the neurons (nerve cell
Being fluent in more than one language is a way to stimulate our brains plasticity. Reading a passage in a language and then joining a conversation in another language forces our brain to constantly restructure itself, reorganize and create new synapses that help our brain to be more alert, more active and highly more responsive. As we learn new vocabulary or a new grammar tense, our brain is constantly adding, saving and relating that new info to previous concepts we have learnt so that our brains plasticity if always put to the test. ...
What is neuroplasticity? Here you can read more about the theory & psychology of neuroplasticity + the best books, TED talks & exercises.
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It has been clear for almost two decades that cortical representations in adult animals are not fixed entities, but rather, are dynamic and are continuously modified by experience. The cortex can preferentially allocate area to represent the particular peripheral input sources that are proportionall …
Biological systems have both robustness and plasticity, a property that distinguish them from artificial systems and is essential for their survival. Biological systems generally exhibit robustness to various perturbations, including the noise in gene/protein expressions and unexpected environmental changes. At the same time, they are plastic to the surrounding environment, changing their state through processes like adaptation, evolution and cell differentiation. Although the coexistence of robustness and plasticity can be understood as a dynamic property of complex and interacting networks consisting of a large number of components, the mechanisms responsible for the coexistence are largely unknown. Thus, the research aim of our team is to understand these mechanisms in biological systems. We have hypothesized that to maintain robustness and plasticity, there exists an interplay between different hierarchical layers in the systems. For example, in the development of multicellular organisms, ...
Piggybacking on Vaughan Bells account of how the word "neuroplasticity" is abused in the public sphere, heres one specific example from to show how fuzzy the picture really is. This particular study by Minerbi et al, available via open access here, measures the structural changes to synapses over a fairly long time frame (~ 5 days) in the presence and absence of electrical input ...
The only thing that is constant in todays world is change. Thats why we invest in long-term relationships to help you design, manage and execute lasting change.
Dendrin, 0.1 mg. Synaptic plasticity and memory formation involve remodeling of the postsynaptic cytoskeleton, a process that is in part based on both local translation of dendritic mRNAs and synaptic recruitment of newly synthesized proteins.
The teams findings describe for the first time the changes that take place in the genetic material of excitatory neurons in the hippocampus of adult mice when they activate.
Investigating the Structural Plasticity of a Cytochrome P450: Three-Dimensional Structures of P450 Eryk and Binding to its Physiological Substrate ...
Activation of the gene product (e.g. receptor) or blockade thereof directly modulates postsynaptic basic function/plasticity events ...
In the mammalian dentate gyrus (DG) neurogenesis continues throughout life. Accumulating evidence suggests a unique contribution of adult-generated neurons in DG synaptic plasticity and hippocampal-mediated learning and memory functions. However, the precise involvement of adult neurogenesis to disease-related cognitive deficits still remains unclear. Intellectual disabilities are the most striking clinical features of Down Syndrome (DS) and are characterized by learning deficits and memory impairment, particularly in hippocampus-related functions. Accordingly, the Ts65Dn mouse model of DS recapitulate many hippocampal cognitive deficits of the human syndrome, and also show decreased adult neurogenesis and impaired DG synaptic plasticity. To elucidate the contribution of faulty adult neurogenesis to DG synaptic plasticity deficits and memory impairment in DS we have treated adult Ts65Dn mice with lithium, a widely used mood stabilizer that also promotes neurogenesis. Results showed that chronic ...
Research Interests The future aint what it used to be - Yogi Berra It is precisely because the future is unpredictable that the mammalian brain has evolved the capacity to acquire new information through sensory experiences, store this information as memories, and rapidly retrieve this information to modify behavior. But how do novel sensory experiences embed themselves in the fabric of the brain to form memories? This question drives the research in my laboratory, which examines the cellular and synaptic mechanisms of experience-dependent plasticity in the neocortex. Specifically, I am interested in understanding i) where experience-dependent plasticity is initiated in the cortical circuitry; ii) how experience regulates the growth or retraction of synapses; iii) whether plasticity is restricted to only a subset of synaptic connections; iv) what distinguishes "critical period" plasticity from adult plasticity; v) how synaptic plasticity is altered in the aging and diseased brain. Techniques: To ...
Previous studies have reported primary auditory cortex plasticity following vagus nerve stimulation (VNS) paired with a sound. Does this phenomenon extend to other fields in the auditory pathway? In this podcast, Editor-in-Chief Bill Yates talks with Dr. Michael S. Borland and Dr. Crystal Engineer (both from the University of Texas at Dallas) about their recent study, which is the first to to document both cortical and subcortical plasticity following VNS-sound pairing. Listen to learn about auditory plasticity, potential therapies for auditory processing disorders, and more! Listen Now. August 14, 2019. ...
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 ...
This new research might unite neurobiologists studying circadian rhythms with those studying developmental brain plasticity, Kobayashi notes. It could open inquiries into the role of circadian rhythm genes beyond the visual system, including brain regions that control cognition and social behaviors.. Specifically, the findings may have implications for disorders such as autism and schizophrenia. A number of genes associated with mental illness were expressed differently in the PV-cells of Clock-deficient versus control mice. The Hensch group and others have long proposed a link between neurodevelopmental disorders and timing defects in critical periods of brain plasticity. And finally, factors that influence circadian rhythms-sleep deprivation, seasonal changes limiting sunlight exposure, night shift work, etc.-have been linked to mood disorders.. By implicating circadian rhythm genes in the control of developmental brain plasticity, the new study may help bridge these ideas and suggests that ...
We used the rat visual cortex as a model system to examine the changes in protein synthesis during experience-induced synaptic plasticity. Dark-rearing rats from birth results in a relatively immature visual cortex that maintains the high de- gree of synaptic plasticity characteristic of the critical period (Kirkwood et al., 1995). Exposure of dark-reared rats to light results in a rapid, robust and coordinated burst of experience- driven synaptic plasticity that can be readily monitored at the biochemical and electrophysiological level (Quinlan et al., 1999). In previous work, we showed that visual experience evokes the polyadenylation of ␣-CaMKII mRNA in visual cortex and the elevation of ␣-CaMKII protein in synaptic fractions from this brain region. Moreover, this increase was a direct result of new synthesis because it was sensitive to the translation inhibitor cycloheximide (Wu et al., 1998). Here we show that the experience-induced increase of ␣-CaMKII pro- tein does not require new ...
While stroke-related deaths have decreased in recent years, stroke is still the leading cause of long-term disability in the United States. Adequate rehabilitation is dependant upon plasticity, a multidimensional and adaptive process underlying recovery of function in both the human and rodent brain. The complexity of processes underlying plasticity in the central nervous system is still largely unknown, but manipulating this spontaneous state of the healing brain is of the utmost importance as it will allow maximum therapeutic effect. Characterization of lesion-induced local and remote rewiring, initial behavioral deficit and their long-term relationships to behavioral outcome are required to fill some of the gaps in our understanding of brain repair mechanisms after stroke. The experiments outlined in this dissertation take advantage of hypothesized neuroplasticity foundations of learning and memory, as well as an established model of forelimb motor cortex injury in rats in order to examine ...
article{ef532af8-d218-4166-9ec2-b39930c591ef, abstract = {,p,Following stroke, complete cellular death in the ischemic brain area may ensue, with remaining brain areas undergoing tissue remodelling to various degrees. Experience-dependent brain plasticity exerted through an enriched environment (EE) promotes remodelling after central nervous system injury, such as stroke. Post-stroke tissue reorganization is modulated by growth inhibitory molecules differentially expressed within the ischemic hemisphere, like chondroitin sulfate proteoglycans found in perineuronal nets (PNNs). PNNs in the neocortex predominantly enwrap parvalbumin-containing GABAergic (PV/GABA) neurons, important in sensori-information processing. Here, we investigate how extracellular matrix (ECM) proteases and their inhibitors may participate in the regulation of PNN integrity during stroke recovery. Rats were subjected to photothrombotic stroke in the motor cortex, and functional deficits were assessed at 7 days of recovery. ...
Resum: Although there is a decline in brain plasticity across lifespan, neurons in certain areas of the adult brain retain the ability to undergo synaptic, dendritic and spine remodeling in response to different stimuli. This neuronal structural plasticity seems to be the basis for many cognitive processes and it is crucial for adaptive responses to aversive experiences and recovery from brain damage and disease. Among the numerous candidate molecules that have been identified for mediating this neuronal remodeling, cell adhesion molecules and, specially, the neural cell adhesion molecule (NCAM), are of particular interest. The addition of polysialic acid (PSA) to the NCAM is critical for the structural changes that underlie plasticity; not only because it prevents both homotypic and heterotypic NCAM bindings (anti-adhesive properties) but also because it interacts with a large number of molecules and signaling pathways that regulate synaptic strength. In consonance with this fact, PSA-NCAM ...
Abstract. It is now accepted that immune molecules are not only present within the brain during pathology but they exert physiological functions in the "healthy" brain as well. Increasing evidence points to a neuro-modulatory role of cytokines and chemokines (CHEMOtactic cytoKINES) in basal transmission and plasticity processes where signaling between peri-synaptic astrocytes, microglia and neurons plays an important role. Nevertheless, the exact mechanisms as to how cytokines, and in particular chemokines, participate in the molecular and cellular processes thought to subserve memory formation, plasticity processes and responsiveness to environmental stimuli remain to be clarified. Interestingly, in in vitro preparations, molecules like TNF-a, interleukin (IL)-1ß, IL-6, CX3CL1, CXCL12, CCL2 and CCL3 are implicated in synaptic formation and scaling, in modulation of glutamatergic transmission, in plasticity and neurogenesis, in particular in the hippocampus. The hippocampus is an extremely ...
Author Summary Recent brain imaging and neurophysiological studies suggest that the striatum, the start of the basal ganglia circuit, plays a major role in value-based decision making and behavioral disorders such as drug addiction. The plasticity of synaptic input from the cerebral cortex to output neurons of the striatum, which are medium spiny neurons, depends on interactions between glutamate input from the cortex and dopaminergic input from the midbrain. It also links sensory and cognitive states in the cortex with reward-oriented action outputs. The mechanisms involved in molecular cascades that transmit glutamate and dopamine inputs to changes in postsynaptic glutamate receptors are very complex and it is difficult to intuitively understand the mechanism. Therefore, a biochemical network model was constructed, and computer simulations were performed. The model reproduced dopamine-dependent and calcium-dependent forms of long-term depression (LTD) and potentiation (LTP) of corticostriatal synapses
Tinnitus is a phantom auditory sensation that reduces quality of life for millions of people worldwide, and for which there is no medical cure. Most cases of tinnitus are associated with hearing loss caused by ageing or noise exposure. Exposure to loud recreational sound is common among the young, and this group are at increasing risk of developing tinnitus.
The world was originally introduced to the concept of synaptic plasticity over 60 years ago, when Dr. Donald Hebb first clearly defined a physiological mechanism for learning and memory in his seminal work "The Organization of Behavior". It took another 20 years for Bliss and Lomo to scientifically validate Hebbs postulate, and show that neurons could alter their ability to communicate with one another in a persistent manner. Together, these works started off what has grown to become the field of synaptic plasticity. The years following the initial discovery were exciting times for learning and memory young researchers like myself, and each discovery over the next 20 years seemed to push us closer to elucidating the biological mechanisms responsible for memory formation. This seemed particularly true in the mid-1980s when the NMDA receptor was being heralded as the key to learning and memory processes. However, more recently it has become obvious that the activation of membrane receptors is ...
His recommendations for healthy life (brisk walking, entertaining sporting activities, etc.) can be found in many books. This is supposed to be a book on neuroplasticity. Unfortunately, you hardly find real recommendations on how we can handle problems by using neuroplasticity tools. Title of the book and chapters do not reflect the real subject ...
The trajectory of the somatic membrane potential of a cortical neuron exactly reflects the computations performed on its afferent inputs. However, the spikes of such a neuron are a very low-dimensional and discrete projection of this continually evolving signal. We explored the possibility that the neurons efferent synapses perform the critical computational step of estimating the membrane potential trajectory from the spikes. We found that short-term changes in synaptic efficacy can be interpreted as implementing an optimal estimator of this trajectory. Short-term depression arose when presynaptic spiking was sufficiently intense as to reduce the uncertainty associated with the estimate; short-term facilitation reflected structural features of the statistics of the presynaptic neuron such as up and down states. Our analysis provides a unifying account of a powerful, but puzzling, form of plasticity.. ...
GABAergic (GABA = gamma-aminobutyric acid) neurons from different brain regions contain high levels of parvalbumin, both in their soma and in their neurites. Parvalbumin is a slow Ca(2+) buffer that may affect the amplitude and time course of intracellular Ca(2+) transients in terminals after an action potential, and hence may regulate short-term synaptic plasticity. To test this possibility, we have applied paired-pulse stimulations (with 30- to 300-ms intervals) at GABAergic synapses between interneurons and Purkinje cells, both in wild-type (PV+/+) mice and in parvalbumin knockout (PV-/-) mice. We observed paired-pulse depression in PV+/+ mice, but paired-pulse facilitation in PV-/- mice. In paired recordings of connected interneuron-Purkinje cells, dialysis of the presynaptic interneuron with the slow Ca(2+) buffer EGTA (1 mM) rescues paired-pulse depression in PV-/- mice. These data show that parvalbumin potently modulates short-term synaptic plasticity. ...
Valentina received her Ph.D. in Neuroscience from Tor Vergata University (Rome), where she explored the role of FMRP in the regulation of transport, translation and stability of dendritic mRNAs. Later she worked extensively on learning-dependent synaptic plasticity at the Hospital for Sick Children, Toronto.. Valentina ...
TY - CHAP. T1 - Translating memories. T2 - The role of protein biosynthesis in synpatic plasticity. AU - Westmark, Cara J.. AU - Malter, James S.. PY - 2009/1/1. Y1 - 2009/1/1. N2 - The 1990s, "The Decade of the Brain", resulted in major scientific advances involving brain imaging, gene therapy, brain/robotic interfacing and the neurobiology and molecular biology of learning and memory. However, despite these critical insights, we still do not know exactly how thoughts or memories are formed or stored in the brain, which leaves much exciting research for the twenty-first and probably centuries to come. This review will elaborate on recent advances in the field of protein biosynthesis as related to synaptic plasticity. We will discuss the molecular players (RNA binding proteins and neuronal mRNAs), the signal transduction pathways that have been implicated in learning and memory and how localized translation of selected mRNAs is involved in synaptic plasticity. We will also discuss the pathology ...
Dopamine-dependent long-term depression at subthalamo-nigral synapses is lost in experimental parkinsonism.: Impairments of synaptic plasticity are a hallmark o
It is an open question how the multiple special and temporal scales involved in intracellular Ca2+ handling within the STDP models affect the plasticity outcomes predicted by these models. Hebbian or associative plasticity is triggered by postsynaptic Ca2+ influx which activates calmodulin and CaMKII. The influx of Ca2+ through voltage-dependent NMDA receptors and Ca2+ channels is regulated by Ca2+ -activated K+ channels (SK-channels) providing negative feedback regulation of postsynaptic [Ca2+]. Using 3-dimensional modelling of Ca2+ and calmodulin dynamics within dendritic spines we show that the non-linear relationship between Ca2+ influx and calmodulin activation endows SK-channels with the ability to "gate" calmodulin activation and therefore the induction of Hebbian synaptic plasticity. Since SK-channels are inhibited by several neuro-modulator receptors including acetylcholine and noradrenaline, the gating of synaptic plasticity by SK-channels could represent a common mechanism by which ...