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Sample records for bidirectional synaptic plasticity

  1. Pannexin 1 Regulates Bidirectional Hippocampal Synaptic Plasticity in Adult Mice

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    Alvaro O. Ardiles

    2014-10-01

    Full Text Available The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR composition of GluN2 subunits. Pannexin 1 (Panx1, a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP, it remains unknown whether these channels also modulate long-term depression (LTD or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory.

  2. Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice

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    Ardiles, Alvaro O.; Flores-Muñoz, Carolina; Toro-Ayala, Gabriela; Cárdenas, Ana M.; Palacios, Adrian G.; Muñoz, Pablo; Fuenzalida, Marco; Sáez, Juan C.; Martínez, Agustín D.

    2014-01-01

    The threshold for bidirectional modification of synaptic plasticity is known to be controlled by several factors, including the balance between protein phosphorylation and dephosphorylation, postsynaptic free Ca2+ concentration and NMDA receptor (NMDAR) composition of GluN2 subunits. Pannexin 1 (Panx1), a member of the integral membrane protein family, has been shown to form non-selective channels and to regulate the induction of synaptic plasticity as well as hippocampal-dependent learning. Although Panx1 channels have been suggested to play a role in excitatory long-term potentiation (LTP), it remains unknown whether these channels also modulate long-term depression (LTD) or the balance between both types of synaptic plasticity. To study how Panx1 contributes to excitatory synaptic efficacy, we examined the age-dependent effects of eliminating or blocking Panx1 channels on excitatory synaptic plasticity within the CA1 region of the mouse hippocampus. By using different protocols to induce bidirectional synaptic plasticity, Panx1 channel blockade or lack of Panx1 were found to enhance LTP, whereas both conditions precluded the induction of LTD in adults, but not in young animals. These findings suggest that Panx1 channels restrain the sliding threshold for the induction of synaptic plasticity and underlying brain mechanisms of learning and memory. PMID:25360084

  3. Orexin A induces bidirectional modulation of synaptic plasticity: Inhibiting long-term potentiation and preventing depotentiation.

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    Lu, Guan-Ling; Lee, Chia-Hsu; Chiou, Lih-Chu

    2016-08-01

    The orexin system consists of two peptides, orexin A and B and two receptors, OX1R and OX2R. It is implicated in learning and memory regulation while controversy remains on its role in modulating hippocampal synaptic plasticity in vivo and in vitro. Here, we investigated effects of orexin A on two forms of synaptic plasticity, long-term potentiation (LTP) and depotentiation of field excitatory postsynaptic potentials (fEPSPs), at the Schaffer Collateral-CA1 synapse of mouse hippocampal slices. Orexin A (≧30 nM) attenuated LTP induced by theta burst stimulation (TBS) in a manner antagonized by an OX1R (SB-334867), but not OX2R (EMPA), antagonist. Conversely, at 1 pM, co-application of orexin A prevented the induction of depotentiation induced by low frequency stimulation (LFS), i.e. restoring LTP. This re-potentiation effect of sub-nanomolar orexin A occurred at LFS of 1 Hz, but not 2 Hz, and with LTP induced by either TBS or tetanic stimulation. It was significantly antagonized by SB-334867, EMPA and TCS-1102, selective OX1R, OX2R and dual OXR antagonists, respectively, and prevented by D609, SQ22536 and H89, inhibitors of phospholipase C (PLC), adenylyl cyclase (AC) and protein kinase A (PKA), respectively. LFS-induced depotentiation was antagonized by blockers of NMDA, A1-adenosine and type 1/5 metabotropic glutamate (mGlu1/5) receptors, respectively. However, orexin A (1 pM) did not affect chemical-induced depotentiation by agonists of these receptors. These results suggest that orexin A bidirectionally modulates hippocampal CA1 synaptic plasticity, inhibiting LTP via OX1Rs at moderate concentrations while inducing re-potentiation via OX1Rs and OX2Rs, possibly through PLC and AC-PKA signaling at sub-nanomolar concentrations. PMID:26965217

  4. Bidirectional synaptic plasticity in intercalated amygdala neurons and the extinction of conditioned fear responses.

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    Royer, S; Paré, D

    2002-01-01

    Classical fear conditioning is believed to result from potentiation of conditioned synaptic inputs in the basolateral amygdala. That is, the conditioned stimulus would excite more neurons in the central nucleus and, via their projections to the brainstem and hypothalamus, evoke fear responses. However, much data suggests that extinction of fear responses does not depend on the reversal of these changes but on a parallel NMDA-dependent learning that competes with the first one. Because they control impulse traffic from the basolateral amygdala to the central nucleus, GABAergic neurons of the intercalated cell masses are ideally located to implement this second learning. Consistent with this hypothesis, the present study shows that low- and high-frequency stimulation of basolateral afferents respectively induce long-term depression (LTD) and potentiation (LTP) of responses in intercalated cells. Moreover, induction of LTP and LTD is prevented by application of an NMDA antagonist. To determine how these activity-dependent changes are expressed, we tested whether LTD and LTP induction are associated with modifications in paired-pulse facilitation, an index of transmitter release probability. Only LTP induction was associated with a change in paired-pulse facilitation. Depotentiation of previously potentiated synapses did not revert the modification in paired pulse facilitation, suggesting that LTP is associated with presynaptic alterations, but that LTD and depotentiation depend on postsynaptic changes. Taken together, our results suggest that basolateral synapses onto intercalated neurons can express NMDA-dependent LTP and LTD, consistent with the possibility that intercalated neurons are a critical locus of plasticity for the extinction of conditioned fear responses. Ultimately, these plastic events may prevent conditioned amygdala responses from exciting neurons of the central nucleus, and thus from evoking conditioned fear responses.

  5. Modelling bidirectional modulations in synaptic plasticity: A biochemical pathway model to understand the emergence of long term potentiation (LTP) and long term depression (LTD).

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    He, Yao; Kulasiri, Don; Samarasinghe, Sandhya

    2016-08-21

    Synaptic plasticity induces bidirectional modulations of the postsynaptic response following a synaptic transmission. The long term forms of synaptic plasticity, named long term potentiation (LTP) and long term depression (LTD), are critical for the antithetic functions of the memory system, memory formation and removal, respectively. A common Ca(2+) signalling upstream triggers both LTP and LTD, and the critical proteins and factors coordinating the LTP/LTD inductions are not well understood. We develop an integrated model based on the sub-models of the indispensable synaptic proteins in the emergence of synaptic plasticity to validate and understand their potential roles in the expression of synaptic plasticity. The model explains Ca(2+)/calmodulin (CaM) complex dependent coordination of LTP/LTD expressions by the interactions among the indispensable proteins using the experimentally estimated kinetic parameters. Analysis of the integrated model provides us with insights into the effective timescales of the key proteins and we conclude that the CaM pool size is critical for the coordination between LTP/LTD expressions. PMID:27185535

  6. SCRAPPER regulates the thresholds of long-term potentiation/depression, the bidirectional synaptic plasticity in hippocampal CA3-CA1 synapses.

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    Takagi, Hiroshi; Setou, Mitsutoshi; Ito, Seiji; Yao, Ikuko

    2012-01-01

    SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1. Here, we recorded the induction of long-term potentiation/depression (LTP/LTD) in CA3-CA1 synapses in E3 ubiquitin ligase SCRAPPER-deficient hippocampal slices. Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with larger magnitudes after induction with tetanus stimulation. These findings suggest that SCRAPPER regulates the threshold of bidirectional synaptic plasticity and, therefore, metaplasticity. PMID:23316391

  7. SCRAPPER Regulates the Thresholds of Long-Term Potentiation/Depression, the Bidirectional Synaptic Plasticity in Hippocampal CA3-CA1 Synapses

    Directory of Open Access Journals (Sweden)

    Hiroshi Takagi

    2012-01-01

    Full Text Available SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1. Here, we recorded the induction of long-term potentiation/depression (LTP/LTD in CA3-CA1 synapses in E3 ubiquitin ligase SCRAPPER-deficient hippocampal slices. Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with larger magnitudes after induction with tetanus stimulation. These findings suggest that SCRAPPER regulates the threshold of bidirectional synaptic plasticity and, therefore, metaplasticity.

  8. Impairment of bidirectional synaptic plasticity in the striatum of a mouse model of DYT1 dystonia: role of endogenous acetylcholine

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    Martella, Giuseppina; Tassone, Annalisa; Sciamanna, Giuseppe; Platania, Paola; Cuomo, Dario; Viscomi, Maria Teresa; Bonsi, Paola; Cacci, Emanuele; Biagioni, Stefano; Usiello, Alessandro; Bernardi, Giorgio; Sharma, Nutan

    2009-01-01

    DYT1 dystonia is a severe form of inherited dystonia, characterized by involuntary twisting movements and abnormal postures. It is linked to a deletion in the dyt1 gene, resulting in a mutated form of the protein torsinA. The penetrance for dystonia is incomplete, but both clinically affected and non-manifesting carriers of the DYT1 mutation exhibit impaired motor learning and evidence of altered motor plasticity. Here, we characterized striatal glutamatergic synaptic plasticity in transgenic mice expressing either the normal human torsinA or its mutant form, in comparison to non-transgenic (NT) control mice. Medium spiny neurons recorded from both NT and normal human torsinA mice exhibited normal long-term depression (LTD), whereas in mutant human torsinA littermates LTD could not be elicited. In addition, although long-term potentiation (LTP) could be induced in all the mice, it was greater in magnitude in mutant human torsinA mice. Low-frequency stimulation (LFS) can revert potentiated synapses to resting levels, a phenomenon termed synaptic depotentiation. LFS induced synaptic depotentiation (SD) both in NT and normal human torsinA mice, but not in mutant human torsinA mice. Since anti-cholinergic drugs are an effective medical therapeutic option for the treatment of human dystonia, we reasoned that an excess in endogenous acetylcholine could underlie the synaptic plasticity impairment. Indeed, both LTD and SD were rescued in mutant human torsinA mice either by lowering endogenous acetylcholine levels or by antagonizing muscarinic M1 receptors. The presence of an enhanced acetylcholine tone was confirmed by the observation that acetylcholinesterase activity was significantly increased in the striatum of mutant human torsinA mice, as compared with both normal human torsinA and NT littermates. Moreover, we found similar alterations of synaptic plasticity in muscarinic M2/M4 receptor knockout mice, in which an increased striatal acetylcholine level has been

  9. Synaptic Plasticity and Nociception

    Institute of Scientific and Technical Information of China (English)

    ChenJianguo

    2004-01-01

    Synaptic plasticity is one of the fields that progresses rapidly and has a lot of success in neuroscience. The two major types of synaptie plasticity: long-term potentiation ( LTP and long-term depression (LTD are thought to be the cellular mochanisms of learning and memory. Recently, accumulating evidence suggests that, besides serving as a cellular model for learning and memory, the synaptic plasticity involves in other physiological or pathophysiological processes, such as the perception of pain and the regulation of cardiovascular system. This minireview will focus on the relationship between synaptic plasticity and nociception.

  10. Optogenetics and synaptic plasticity.

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    Xie, Yu-feng; Jackson, Michael F; Macdonald, John F

    2013-11-01

    The intricate and complex interaction between different populations of neurons in the brain has imposed limits on our ability to gain detailed understanding of synaptic transmission and its integration when employing classical electrophysiological approaches. Indeed, electrical field stimulation delivered via traditional microelectrodes does not permit the targeted, precise and selective control of neuronal activity amongst a varied population of neurons and their inputs (eg, cholinergic, dopaminergic or glutamatergic neurons). Recently established optogenetic techniques overcome these limitations allowing precise control of the target neuron populations, which is essential for the elucidation of the neural substrates underlying complex animal behaviors. Indeed, by introducing light-activated channels (ie, microbial opsin genes) into specific neuronal populations, optogenetics enables non-invasive optical control of specific neurons with milliseconds precision. These approaches can readily be applied to freely behaving live animals. Recently there is increased interests in utilizing optogenetics tools to understand synaptic plasticity and learning/memory. Here, we summarize recent progress in applying optogenetics in in the study of synaptic plasticity.

  11. SCRAPPER Regulates the Thresholds of Long-Term Potentiation/Depression, the Bidirectional Synaptic Plasticity in Hippocampal CA3-CA1 Synapses

    OpenAIRE

    Hiroshi Takagi; Mitsutoshi Setou; Seiji Ito; Ikuko Yao

    2012-01-01

    SCRAPPER, which is an F-box protein encoded by FBXL20, regulates the frequency of the miniature excitatory synaptic current through the ubiquitination of Rab3-interacting molecule 1. Here, we recorded the induction of long-term potentiation/depression (LTP/LTD) in CA3-CA1 synapses in E3 ubiquitin ligase SCRAPPER-deficient hippocampal slices. Compared to wild-type mice, Scrapper-knockout mice exhibited LTDs with smaller magnitudes after induction with low-frequency stimulation and LTPs with la...

  12. Emergence of Functional Specificity in Balanced Networks with Synaptic Plasticity.

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    Sadra Sadeh

    2015-06-01

    Full Text Available In rodent visual cortex, synaptic connections between orientation-selective neurons are unspecific at the time of eye opening, and become to some degree functionally specific only later during development. An explanation for this two-stage process was proposed in terms of Hebbian plasticity based on visual experience that would eventually enhance connections between neurons with similar response features. For this to work, however, two conditions must be satisfied: First, orientation selective neuronal responses must exist before specific recurrent synaptic connections can be established. Second, Hebbian learning must be compatible with the recurrent network dynamics contributing to orientation selectivity, and the resulting specific connectivity must remain stable for unspecific background activity. Previous studies have mainly focused on very simple models, where the receptive fields of neurons were essentially determined by feedforward mechanisms, and where the recurrent network was small, lacking the complex recurrent dynamics of large-scale networks of excitatory and inhibitory neurons. Here we studied the emergence of functionally specific connectivity in large-scale recurrent networks with synaptic plasticity. Our results show that balanced random networks, which already exhibit highly selective responses at eye opening, can develop feature-specific connectivity if appropriate rules of synaptic plasticity are invoked within and between excitatory and inhibitory populations. If these conditions are met, the initial orientation selectivity guides the process of Hebbian learning and, as a result, functionally specific and a surplus of bidirectional connections emerge. Our results thus demonstrate the cooperation of synaptic plasticity and recurrent dynamics in large-scale functional networks with realistic receptive fields, highlight the role of inhibition as a critical element in this process, and paves the road for further computational

  13. Synaptic vesicle proteins and active zone plasticity

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    Robert J Kittel

    2016-04-01

    Full Text Available Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone. The complex molecular architecture of active zones mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of active zones vary significantly, even for a given connection. Thus, there appear to be distinct active zone states, which fundamentally influence neuronal communication by controlling the positioning and release of synaptic vesicles. Vice versa, recent evidence has revealed that synaptic vesicle components also modulate organizational states of the active zone.The protein-rich cytomatrix at the active zone (CAZ provides a structural platform for molecular interactions guiding vesicle exocytosis. Studies in Drosophila have now demonstrated that the vesicle proteins Synaptotagmin-1 (Syt1 and Rab3 also regulate glutamate release by shaping differentiation of the CAZ ultrastructure. We review these unexpected findings and discuss mechanistic interpretations of the reciprocal relationship between synaptic vesicles and active zone states, which has heretofore received little attention.

  14. Synaptic Vesicle Proteins and Active Zone Plasticity.

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    Kittel, Robert J; Heckmann, Manfred

    2016-01-01

    Neurotransmitter is released from synaptic vesicles at the highly specialized presynaptic active zone (AZ). The complex molecular architecture of AZs mediates the speed, precision and plasticity of synaptic transmission. Importantly, structural and functional properties of AZs vary significantly, even for a given connection. Thus, there appear to be distinct AZ states, which fundamentally influence neuronal communication by controlling the positioning and release of synaptic vesicles. Vice versa, recent evidence has revealed that synaptic vesicle components also modulate organizational states of the AZ. The protein-rich cytomatrix at the active zone (CAZ) provides a structural platform for molecular interactions guiding vesicle exocytosis. Studies in Drosophila have now demonstrated that the vesicle proteins Synaptotagmin-1 (Syt1) and Rab3 also regulate glutamate release by shaping differentiation of the CAZ ultrastructure. We review these unexpected findings and discuss mechanistic interpretations of the reciprocal relationship between synaptic vesicles and AZ states, which has heretofore received little attention.

  15. Bi-directional modulation of AMPA receptor unitary conductance by synaptic activity

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    Matthews Paul

    2004-11-01

    Full Text Available Abstract Background Knowledge of how synapses alter their efficiency of communication is central to the understanding of learning and memory. The most extensively studied forms of synaptic plasticity are long-term potentiation (LTP and its counterpart long-term depression (LTD of AMPA receptor-mediated synaptic transmission. In the CA1 region of the hippocampus, it has been shown that LTP often involves a rapid increase in the unitary conductance of AMPA receptor channels. However, LTP can also occur in the absence of any alteration in AMPA receptor unitary conductance. In the present study we have used whole-cell dendritic recording, failures analysis and non-stationary fluctuation analysis to investigate the mechanism of depotentiation of LTP. Results We find that when LTP involves an increase in unitary conductance, subsequent depotentiation invariably involves the return of unitary conductance to pre-LTP values. In contrast, when LTP does not involve a change in unitary conductance then depotentiation also occurs in the absence of any change in unitary conductance, indicating a reduction in the number of activated receptors as the most likely mechanism. Conclusions These data show that unitary conductance can be bi-directionally modified by synaptic activity. Furthermore, there are at least two distinct mechanisms to restore synaptic strength from a potentiated state, which depend upon the mechanism of the previous potentiation.

  16. Synaptic plasticity and the warburg effect

    KAUST Repository

    Magistretti, Pierre J.

    2014-01-01

    Functional brain imaging studies show that in certain brain regions glucose utilization exceeds oxygen consumption, indicating the predominance of aerobic glycolysis. In this issue, Goyal et al. (2014) report that this metabolic profile is associated with an enrichment in the expression of genes involved in synaptic plasticity and remodeling processes. © 2014 Elsevier Inc.

  17. Calcineurin, Synaptic Plasticity, and Memory

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    Carl Weitlauf

    2001-01-01

    Full Text Available A long-held hypothesis in neuroscience holds that learning and memory mechanisms involve lasting changes in synaptic weights. Multiple mechanisms for producing such changes exist, of which NMDA-receptor–dependent long-term potentiation (LTP is the most widely studied. Curiously, the relatively simple hypothesis that LTP plays a role in learning and memory has proven difficult to test. A current experimental strategy is to generate genetically altered mice with mutations in genes thought to be involved in LTP and assess the effects of these mutations both on LTP and animal behavior[1,2]. A difficulty associated with these approaches has been that they are not temporally or spatially refined. To alleviate this problem, Dr. Isabelle Mansuy and colleagues used an inducible and reversible transgene expression system in which transgene expression could be controlled on a week-to-week timescale to assess the effects of genetic reduction of the activity of a protein phosphatase known as calcineurin or PP2B in adult mouse forebrain[3,4].

  18. Emerging Links between Homeostatic Synaptic Plasticity and Neurological Disease

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    Dion eDickman

    2013-11-01

    Full Text Available Homeostatic signaling systems are ubiquitous forms of biological regulation, having been studied for hundreds of years in the context of diverse physiological processes including body temperature and osmotic balance. However, only recently has this concept been brought to the study of excitatory and inhibitory electrical activity that the nervous system uses to establish and maintain stable communication. Synapses are a primary target of neuronal regulation with a variety of studies over the past 15 years demonstrating that these cellular junctions are under bidirectional homeostatic control. Recent work from an array of diverse systems and approaches has revealed exciting new links between homeostatic synaptic plasticity and a variety of seemingly disparate neurological and psychiatric diseases. These include autism spectrum disorders, intellectual disabilities, schizophrenia, and Fragile X Syndrome. Although the molecular mechanisms through which defective homeostatic signaling may lead to disease pathogenesis remain unclear, rapid progress is likely to be made in the coming years using a powerful combination of genetic, imaging, electrophysiological, and next generation sequencing approaches. Importantly, understanding homeostatic synaptic plasticity at a cellular and molecular level may lead to developments in new therapeutic innovations to treat these diseases. In this review we will examine recent studies that demonstrate homeostatic control of postsynaptic protein translation, retrograde signaling, and presynaptic function that may contribute to the etiology of complex neurological and psychiatric diseases.

  19. Filamentary Switching: Synaptic Plasticity through Device Volatility

    CERN Document Server

    La Barbera, Selina; Alibart, Fabien

    2015-01-01

    Replicating the computational functionalities and performances of the brain remains one of the biggest challenges for the future of information and communication technologies. Such an ambitious goal requires research efforts from the architecture level to the basic device level (i.e., investigating the opportunities offered by emerging nanotechnologies to build such systems). Nanodevices, or, more precisely, memory or memristive devices, have been proposed for the implementation of synaptic functions, offering the required features and integration in a single component. In this paper, we demonstrate that the basic physics involved in the filamentary switching of electrochemical metallization cells can reproduce important biological synaptic functions that are key mechanisms for information processing and storage. The transition from short- to long-term plasticity has been reported as a direct consequence of filament growth (i.e., increased conductance) in filamentary memory devices. In this paper, we show tha...

  20. Fragile X mental retardation protein and synaptic plasticity

    OpenAIRE

    Sidorov, Michael S.; Auerbach, Benjamin D.; Bear, Mark F.

    2013-01-01

    Loss of the translational repressor FMRP causes Fragile X syndrome. In healthy neurons, FMRP modulates the local translation of numerous synaptic proteins. Synthesis of these proteins is required for the maintenance and regulation of long-lasting changes in synaptic strength. In this role as a translational inhibitor, FMRP exerts profound effects on synaptic plasticity.

  1. Nicotinic mechanisms influencing synaptic plasticity in the hippocampus

    Institute of Scientific and Technical Information of China (English)

    Andon Nicholas PLACZEK; Tao A ZHANG; John Anthony DANI

    2009-01-01

    Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the hippocampus, and nicotinic signaling plays an important role in neuronal function. In the context of learning and memory related behaviors associated with hippocampal function, a potentially significant feature of nAChR activity is the impact it has on synaptic plasticity. Synaptic plasticity in hippocampal neurons has long been considered a contributing cellular mechanism of learning and memory. These same kinds of cellular mechanisms are a factor in the development of nicotine addiction. Nicotinic signaling has been demonstrated by in vitro studies to affect synaptic plasticity in hippocampal neurons via multiple steps, and the signaling has also been shown to evoke synaptic plasticity in vivo. This review focuses on the nAChRs subtypes that contribute to hippocampal synaptic plasticity at the cellular and circuit level. It also considers nicotinic influences over long-term changes in the hippocampus that may contribute to addiction.

  2. Spikes Synchronization in Neural Networks with Synaptic Plasticity

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    Borges, Rafael R; Batista, Antonio M; Caldas, Iberê L; Borges, Fernando S; Lameu, Ewandson L

    2015-01-01

    In this paper, we investigated the neural spikes synchronisation in a neural network with synaptic plasticity and external perturbation. In the simulations the neural dynamics is described by the Hodgkin Huxley model considering chemical synapses (excitatory) among neurons. According to neural spikes synchronisation is expected that a perturbation produce non synchronised regimes. However, in the literature there are works showing that the combination of synaptic plasticity and external perturbation may generate synchronised regime. This article describes the effect of the synaptic plasticity on the synchronisation, where we consider a perturbation with a uniform distribution. This study is relevant to researches of neural disorders control.

  3. The impact of synapsins on synaptic plasticity and cognitive behaviors

    Institute of Scientific and Technical Information of China (English)

    Lin ZHANG; Zhong-Xin ZHAO

    2006-01-01

    Synapsins are a family of phosphoproteins specifically associated with the cytoplasmic surface of the synaptic vesicle membrane, appearing to regulate neurotransmitter release, the formation and maintenance of synaptic contacts.They could induce the change of the synaptic plasticity to regulate various adaptation reactions, and change the cognitive behaviors. So we presume that if some cognitive behavior are damaged, synapsins would be changed as well. This gives us a new recognition of better diagnosis and therapy of cognitive disorder desease.

  4. The Ubiquitin-Proteasome Pathway and Synaptic Plasticity

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    Hegde, Ashok N.

    2010-01-01

    Proteolysis by the ubiquitin-proteasome pathway (UPP) has emerged as a new molecular mechanism that controls wide-ranging functions in the nervous system, including fine-tuning of synaptic connections during development and synaptic plasticity in the adult organism. In the UPP, attachment of a small protein, ubiquitin, tags the substrates for…

  5. Corticosteroid Regulation of Synaptic Plasticity in the Hippocampus

    OpenAIRE

    Nicola Maggio; Menahem Segal

    2010-01-01

    Stress, via release of steroid hormones, has been shown to affect several cellular functions in the brain, including synaptic receptors and ion channels. As such, corticosteroids were reported to modulate plasticity, expressed as long-term changes in reactivity to afferent stimulation. The classical view of the effects of stress on synaptic plasticity and cognitive functions assumes an inverted U-shape curve, such that a low stress level facilitates and a high stress level (i.e., corticostero...

  6. Mapping homeostatic synaptic plasticity using cable properties of dendrites.

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    Queenan, B N; Lee, K J; Tan, H; Huganir, R L; Vicini, S; Pak, D T S

    2016-02-19

    When chronically silenced, cortical and hippocampal neurons homeostatically upregulate excitatory synaptic function. However, the subcellular position of such changes on the dendritic tree is not clear. We exploited the cable-filtering properties of dendrites to derive a parameter, the dendritic filtering index (DFI), to map the spatial distribution of synaptic currents. Our analysis indicates that young rat cortical neurons globally scale AMPA receptor-mediated currents, while mature hippocampal neurons do not, revealing distinct homeostatic strategies between brain regions and developmental stages. The DFI presents a useful tool for mapping the dendritic origin of synaptic currents and the location of synaptic plasticity changes.

  7. Activity-dependent synaptic plasticity of a chalcogenide electronic synapse for neuromorphic systems.

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    Li, Yi; Zhong, Yingpeng; Zhang, Jinjian; Xu, Lei; Wang, Qing; Sun, Huajun; Tong, Hao; Cheng, Xiaoming; Miao, Xiangshui

    2014-01-01

    Nanoscale inorganic electronic synapses or synaptic devices, which are capable of emulating the functions of biological synapses of brain neuronal systems, are regarded as the basic building blocks for beyond-Von Neumann computing architecture, combining information storage and processing. Here, we demonstrate a Ag/AgInSbTe/Ag structure for chalcogenide memristor-based electronic synapses. The memristive characteristics with reproducible gradual resistance tuning are utilised to mimic the activity-dependent synaptic plasticity that serves as the basis of memory and learning. Bidirectional long-term Hebbian plasticity modulation is implemented by the coactivity of pre- and postsynaptic spikes, and the sign and degree are affected by assorted factors including the temporal difference, spike rate and voltage. Moreover, synaptic saturation is observed to be an adjustment of Hebbian rules to stabilise the growth of synaptic weights. Our results may contribute to the development of highly functional plastic electronic synapses and the further construction of next-generation parallel neuromorphic computing architecture. PMID:24809396

  8. Cerebellar Synaptic Plasticity and the Credit Assignment Problem.

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    Jörntell, Henrik

    2016-04-01

    The mechanism by which a learnt synaptic weight change can contribute to learning or adaptation of brain function is a type of credit assignment problem, which is a key issue for many parts of the brain. In the cerebellum, detailed knowledge not only of the local circuitry connectivity but also of the topography of different sources of afferent/external information makes this problem particularly tractable. In addition, multiple forms of synaptic plasticity and their general rules of induction have been identified. In this review, we will discuss the possible roles of synaptic and cellular plasticity at specific locations in contributing to behavioral changes. Focus will be on the parts of the cerebellum that are devoted to limb control, which constitute a large proportion of the cortex and where the knowledge of the external connectivity is particularly well known. From this perspective, a number of sites of synaptic plasticity appear to primarily have the function of balancing the overall level of activity in the cerebellar circuitry, whereas the locations at which synaptic plasticity leads to functional changes in terms of limb control are more limited. Specifically, the postsynaptic forms of long-term potentiation (LTP) and long-term depression (LTD) at the parallel fiber synapses made on interneurons and Purkinje cells, respectively, are the types of plasticity that mediate the widest associative capacity and the tightest link between the synaptic change and the external functions that are to be controlled. PMID:25417189

  9. Synaptic plasticity functions in an organic electrochemical transistor

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    Gkoupidenis, Paschalis; Schaefer, Nathan; Strakosas, Xenofon; Fairfield, Jessamyn A.; Malliaras, George G.

    2015-12-01

    Synaptic plasticity functions play a crucial role in the transmission of neural signals in the brain. Short-term plasticity is required for the transmission, encoding, and filtering of the neural signal, whereas long-term plasticity establishes more permanent changes in neural microcircuitry and thus underlies memory and learning. The realization of bioinspired circuits that can actually mimic signal processing in the brain demands the reproduction of both short- and long-term aspects of synaptic plasticity in a single device. Here, we demonstrate the implementation of neuromorphic functions similar to biological memory, such as short- to long-term memory transition, in non-volatile organic electrochemical transistors (OECTs). Depending on the training of the OECT, the device displays either short- or long-term plasticity, therefore, exhibiting non von Neumann characteristics with merged processing and storing functionalities. These results are a first step towards the implementation of organic-based neuromorphic circuits.

  10. Morphological plasticity of astroglia: Understanding synaptic microenvironment

    OpenAIRE

    Heller, J. P.; Rusakov, D. A.

    2015-01-01

    Memory formation in the brain is thought to rely on the remodeling of synaptic connections which eventually results in neural network rewiring. This remodeling is likely to involve ultrathin astroglial protrusions which often occur in the immediate vicinity of excitatory synapses. The phenomenology, cellular mechanisms, and causal relationships of such astroglial restructuring remain, however, poorly understood. This is in large part because monitoring and probing of the underpinning molecula...

  11. Cell-specific synaptic plasticity induced by network oscillations.

    Science.gov (United States)

    Zarnadze, Shota; Bäuerle, Peter; Santos-Torres, Julio; Böhm, Claudia; Schmitz, Dietmar; Geiger, Jörg Rp; Dugladze, Tamar; Gloveli, Tengis

    2016-01-01

    Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner. PMID:27218453

  12. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity.

    Science.gov (United States)

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

  13. Isoform Specificity of Protein Kinase Cs in Synaptic Plasticity

    Science.gov (United States)

    Sossin, Wayne S.

    2007-01-01

    Protein kinase Cs (PKCs) are implicated in many forms of synaptic plasticity. However, the specific isoform(s) of PKC that underlie(s) these events are often not known. We have used "Aplysia" as a model system in order to investigate the isoform specificity of PKC actions due to the presence of fewer isoforms and a large number of documented…

  14. Spontaneous Activity Drives Local Synaptic Plasticity In Vivo

    NARCIS (Netherlands)

    Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, C.

    2015-01-01

    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 t

  15. Synaptic plasticity%神经突触可塑性

    Institute of Scientific and Technical Information of China (English)

    张强; 叶桂兰

    2002-01-01

    Nervous system is modifiable and more plastic than we thought. Neuronal plasticity or synaptic plasticity is maximal during brain development and still exists in adult brain. In the last ten years, most effort in the study of synaptic plasticity has been putting on activity dependent plasticity, in terms of LTP and LTD, which are thought underlines mechanisms of learning and memory. Here we briefly reviewed the concept of plasticity and summarized the research progresses of some aspects in activity dependent plasticity and developmental plasticity.%脑、神经元、神经突触都具有可塑性.脑发育过程中其可塑性最强,成年脑仍具有可塑性.对神经可塑性的研究,大致可分类为发育可塑性、活动依赖性可塑性、损伤后可塑性以及移植后可塑性.本文概要地介绍了对神经可塑性的理解,发育可塑性的研究视点,以及活动依赖性突触可塑性的研究进展.

  16. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Robert Nisticò

    Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

  17. Spontaneous Activity Drives Local Synaptic Plasticity In Vivo.

    Science.gov (United States)

    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 (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. PMID:26182421

  18. Frequency dependent changes in NMDAR-dependent synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Arvind eKumar

    2011-09-01

    Full Text Available The NMDAR-dependent synaptic plasticity is thought to mediate several forms of learning, and can be induced by spike trains containing a small number of spikes occurring with varying rates and timing, as well as with oscillations. We computed the influence of these variables on the plasticity induced at a single NMDAR containing synapse using a reduced model that was analytically tractable, and these findings were confirmed using detailed, multi-compartment model. In addition to explaining diverse experimental results about the rate and timing dependence of synaptic plasticity, the model made several novel and testable predictions. We found that there was a preferred frequency for inducing long-term potentiation (LTP such that higher frequency stimuli induced lesser LTP, decreasing as 1/f when the number of spikes in the stimulus was kept fixed. Among other things, the preferred frequency for inducing LTP varied as a function of the distance of the synapse from the soma. In fact, same stimulation frequencies could induce LTP or LTD depending on the dendritic location of the synapse. Next, we found that rhythmic stimuli induced greater plasticity then irregular stimuli. Furthermore, brief bursts of spikes significantly expanded the timing dependence of plasticity. Finally, we found that in the ~5-15Hz frequency range both rate- and timing-dependent plasticity mechanisms work synergistically to render the synaptic plasticity most sensitive to spike-timing. These findings provide computational evidence that oscillations can have a profound influence on the plasticity of an NMDAR-dependent synapse, and show a novel role for the dendritic morphology in this process.

  19. Bayesian synaptic plasticity makes predictions about plasticity experiments in vivo

    OpenAIRE

    Aitchison, Laurence; Latham, Peter E.

    2014-01-01

    Humans and other animals learn by updating synaptic weights in the brain. Rapid learning allows animals to adapt quickly to changes in their environment, giving them a large selective advantage. As brains have been evolving for several hundred million years, we might expect biological learning rules to be close to optimal, by exploiting all locally available information in order to learn as rapidly as possible. However, no previously proposed learning rules are optimal in this sense. We there...

  20. Translational regulatory mechanisms in persistent forms of synaptic plasticity.

    Science.gov (United States)

    Kelleher, Raymond J; Govindarajan, Arvind; Tonegawa, Susumu

    2004-09-30

    Memory and synaptic plasticity exhibit distinct temporal phases, with long-lasting forms distinguished by their dependence on macromolecular synthesis. Prevailing models for the molecular mechanisms underlying long-lasting synaptic plasticity have largely focused on transcriptional regulation. However, a growing body of evidence now supports a crucial role for neuronal activity-dependent mRNA translation, which may occur in dendrites for a subset of neuronal mRNAs. Recent work has begun to define the signaling mechanisms coupling synaptic activation to the protein synthesis machinery. The ERK and mTOR signaling pathways have been shown to regulate the activity of the general translational machinery, while the translation of particular classes of mRNAs is additionally controlled by gene-specific mechanisms. Rapid enhancement of the synthesis of a diverse array of neuronal proteins through such mechanisms provides the components necessary for persistent forms of LTP and LTD. These findings have important implications for the synapse specificity and associativity of protein synthesis-dependent changes in synaptic strength. PMID:15450160

  1. Plasticity-Driven Self-Organization under Topological Constraints Accounts for Non-random Features of Cortical Synaptic Wiring.

    Directory of Open Access Journals (Sweden)

    Daniel Miner

    2016-02-01

    Full Text Available Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function. Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random, exhibiting, for example, above-chance bidirectionality and an overrepresentation of certain triangular motifs. Additional evidence suggests a significant distance dependency to connectivity over a local scale of a few hundred microns, and particular patterns of synaptic turnover dynamics, including a heavy-tailed distribution of synaptic efficacies, a power law distribution of synaptic lifetimes, and a tendency for stronger synapses to be more stable over time. Understanding how many of these non-random features simultaneously arise would provide valuable insights into the development and function of the cortex. While previous work has modeled some of the individual features of local cortical wiring, there is no model that begins to comprehensively account for all of them. We present a spiking network model of a rodent Layer 5 cortical slice which, via the interactions of a few simple biologically motivated intrinsic, synaptic, and structural plasticity mechanisms, qualitatively reproduces these non-random effects when combined with simple topological constraints. Our model suggests that mechanisms of self-organization arising from a small number of plasticity rules provide a parsimonious explanation for numerous experimentally observed non-random features of recurrent cortical wiring. Interestingly, similar mechanisms have been shown to endow recurrent networks with powerful learning abilities, suggesting that these mechanism are central to understanding both structure and function of cortical synaptic wiring.

  2. Fragile X Syndrome: Keys to the Molecular Genetics of Synaptic Plasticity

    Science.gov (United States)

    Lombroso, Paul J.; Ogren, Marilee P.

    2008-01-01

    Fragile X syndrome, the most common form of inherited mental retardation is discussed. The relationship between specific impairments in synaptic plasticity and Fragile X syndrome is investigated as it strengthens synaptic contacts between neurons.

  3. The computational power of astrocyte mediated synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Rogier eMin

    2012-11-01

    Full Text Available Research in the last two decades has made clear that astrocytes play a crucial role in the brain beyond their functions in energy metabolism and homeostasis. Many studies have shown that astrocytes can dynamically modulate neuronal excitability and synaptic plasticity, and might participate in higher brain functions like learning and memory. With the plethora of astrocyte-mediated signaling processes described in the literature today, the current challenge is to identify which of these processes happen under what physiological condition, and how this shapes information processing and, ultimately, behavior. To answer these questions will require a combination of advanced physiological, genetical and behavioral experiments. Additionally, mathematical modeling will prove crucial for testing predictions on the possible functions of astrocytes in neuronal networks, and to generate novel ideas as to how astrocytes can contribute to the complexity of the brain. Here, we aim to provide an outline of how astrocytes can interact with neurons. We do this by reviewing recent experimental literature on astrocyte-neuron interactions, discussing the dynamic effects of astrocytes on neuronal excitability and short- and long-term synaptic plasticity. Finally, we will outline the potential computational functions that astrocyte-neuron interactions can serve in the brain. We will discuss how astrocytes could govern metaplasticity in the brain, how they might organize the clustering of synaptic inputs, and how they could function as memory elements for neuronal activity. We conclude that astrocytes can enhance the computational power of neuronal networks in previously unexpected ways.

  4. Astrocytes mediate in vivo cholinergic-induced synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Marta Navarrete

    2012-02-01

    Full Text Available Long-term potentiation (LTP of synaptic transmission represents the cellular basis of learning and memory. Astrocytes have been shown to regulate synaptic transmission and plasticity. However, their involvement in specific physiological processes that induce LTP in vivo remains unknown. Here we show that in vivo cholinergic activity evoked by sensory stimulation or electrical stimulation of the septal nucleus increases Ca²⁺ in hippocampal astrocytes and induces LTP of CA3-CA1 synapses, which requires cholinergic muscarinic (mAChR and metabotropic glutamate receptor (mGluR activation. Stimulation of cholinergic pathways in hippocampal slices evokes astrocyte Ca²⁺ elevations, postsynaptic depolarizations of CA1 pyramidal neurons, and LTP of transmitter release at single CA3-CA1 synapses. Like in vivo, these effects are mediated by mAChRs, and this cholinergic-induced LTP (c-LTP also involves mGluR activation. Astrocyte Ca²⁺ elevations and LTP are absent in IP₃R2 knock-out mice. Downregulating astrocyte Ca²⁺ signal by loading astrocytes with BAPTA or GDPβS also prevents LTP, which is restored by simultaneous astrocyte Ca²⁺ uncaging and postsynaptic depolarization. Therefore, cholinergic-induced LTP requires astrocyte Ca²⁺ elevations, which stimulate astrocyte glutamate release that activates mGluRs. The cholinergic-induced LTP results from the temporal coincidence of the postsynaptic activity and the astrocyte Ca²⁺ signal simultaneously evoked by cholinergic activity. Therefore, the astrocyte Ca²⁺ signal is necessary for cholinergic-induced synaptic plasticity, indicating that astrocytes are directly involved in brain storage information.

  5. Presynaptic active zone density during development and synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Gwenaëlle L Clarke

    2012-02-01

    Full Text Available 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.

  6. The Role of Short Term Synaptic Plasticity in Temporal Coding of Neuronal Networks

    Science.gov (United States)

    Chandrasekaran, Lakshmi

    2008-01-01

    Short term synaptic plasticity is a phenomenon which is commonly found in the central nervous system. It could contribute to functions of signal processing namely, temporal integration and coincidence detection by modulating the input synaptic strength. This dissertation has two parts. First, we study the effects of short term synaptic plasticity…

  7. Histone Deacetylase Inhibition Facilitates Massed Pattern-Induced Synaptic Plasticity and Memory

    Science.gov (United States)

    Pandey, Kiran; Sharma, Kaushik P.; Sharma, Shiv K.

    2015-01-01

    Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well…

  8. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    OpenAIRE

    Masoud Soheili; Mostafa Rezaei Tavirany; Mahmoud Salami

    2015-01-01

    Objective(s): Neurodegenerative Alzheimer’s disease (AD) is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP), an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia) on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extra...

  9. Endocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses

    Directory of Open Access Journals (Sweden)

    María-Paz Viveros

    2007-01-01

    Full Text Available The endocannabinoid system has been involved in the regulation of anxiety, and proposed as an inhibitory modulator of neuronal, behavioral and adrenocortical responses to stressful stimuli. Brain regions such as the amygdala, hippocampus and cortex, which are directly involved in the regulation of emotional behavior, contain high densities of cannabinoid CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic and depressive-like behaviors as well as an altered hypothalamus pituitary adrenal axis activity, whereas enhancement of endocannabinoid signaling produces anxiolytic and antidepressant-like effects. Genetic and pharmacological approaches also support an involvement of endocannabinoids in extinction of aversive memories. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states. Endocannabinoids have emerged as mediators of short- and long- term synaptic plasticity in diverse brain structures. Despite the fact that most of the studies on this field have been performed using in vitro models, endocannabinoid-mediated plasticity might be considered as a plausible candidate underlying some of the diverse physiological functions of the endogenous cannabinoid system, including developmental, affective and cognitive processes. In this paper, we will focus on the functional relevance of endocannabinoid-mediated plasticity within the framework of emotional responses. Alterations of the endocannabinoid system may constitute an important factor in the aetiology of certain neuropsychiatric disorders, and, in turn, enhancers of endocannabinoid signaling could represent a potential therapeutical tool in the treatment of both anxiety and depressive symptoms.

  10. Endocannabinoid system and synaptic plasticity: implications for emotional responses.

    Science.gov (United States)

    Viveros, María-Paz; Marco, Eva-María; Llorente, Ricardo; López-Gallardo, Meritxell

    2007-01-01

    The endocannabinoid system has been involved in the regulation of anxiety, and proposed as an inhibitory modulator of neuronal, behavioral and adrenocortical responses to stressful stimuli. Brain regions such as the amygdala, hippocampus and cortex, which are directly involved in the regulation of emotional behavior, contain high densities of cannabinoid CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic and depressive-like behaviors as well as an altered hypothalamus pituitary adrenal axis activity, whereas enhancement of endocannabinoid signaling produces anxiolytic and antidepressant-like effects. Genetic and pharmacological approaches also support an involvement of endocannabinoids in extinction of aversive memories. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states. Endocannabinoids have emerged as mediators of short- and long-term synaptic plasticity in diverse brain structures. Despite the fact that most of the studies on this field have been performed using in vitro models, endocannabinoid-mediated plasticity might be considered as a plausible candidate underlying some of the diverse physiological functions of the endogenous cannabinoid system, including developmental, affective and cognitive processes. In this paper, we will focus on the functional relevance of endocannabinoid-mediated plasticity within the framework of emotional responses. Alterations of the endocannabinoid system may constitute an important factor in the aetiology of certain neuropsychiatric disorders, and, in turn, enhancers of endocannabinoid signaling could represent a potential therapeutical tool in the treatment of both anxiety and depressive symptoms.

  11. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  12. Spike-Timing–Dependent Synaptic Plasticity and Synaptic Democracy in Dendrites

    Science.gov (United States)

    Gidon, Albert; Segev, Idan

    2009-01-01

    We explored in a computational study the effect of dendrites on excitatory synapses undergoing spike-timing–dependent plasticity (STDP), using both cylindrical dendritic models and reconstructed dendritic trees. We show that even if the initial strength, gpeak, of distal synapses is augmented in a location independent manner, the efficacy of distal synapses diminishes following STDP and proximal synapses would eventually dominate. Indeed, proximal synapses always win over distal synapses following linear STDP rule, independent of the initial synaptic strength distribution in the dendritic tree. This effect is more pronounced as the dendritic cable length increases but it does not depend on the dendritic branching structure. Adding a small multiplicative component to the linear STDP rule, whereby already strong synapses tend to be less potentiated than depressed (and vice versa for weak synapses) did partially “save” distal synapses from “dying out.” Another successful strategy for balancing the efficacy of distal and proximal synapses following STDP is to increase the upper bound for the synaptic conductance (gmax) with distance from the soma. We conclude by discussing an experiment for assessing which of these possible strategies might actually operate in dendrites. PMID:19357339

  13. Spike-timing-dependent synaptic plasticity and synaptic democracy in dendrites.

    Science.gov (United States)

    Gidon, Albert; Segev, Idan

    2009-06-01

    We explored in a computational study the effect of dendrites on excitatory synapses undergoing spike-timing-dependent plasticity (STDP), using both cylindrical dendritic models and reconstructed dendritic trees. We show that even if the initial strength, g(peak), of distal synapses is augmented in a location independent manner, the efficacy of distal synapses diminishes following STDP and proximal synapses would eventually dominate. Indeed, proximal synapses always win over distal synapses following linear STDP rule, independent of the initial synaptic strength distribution in the dendritic tree. This effect is more pronounced as the dendritic cable length increases but it does not depend on the dendritic branching structure. Adding a small multiplicative component to the linear STDP rule, whereby already strong synapses tend to be less potentiated than depressed (and vice versa for weak synapses) did partially "save" distal synapses from "dying out." Another successful strategy for balancing the efficacy of distal and proximal synapses following STDP is to increase the upper bound for the synaptic conductance (g(max)) with distance from the soma. We conclude by discussing an experiment for assessing which of these possible strategies might actually operate in dendrites.

  14. The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens

    OpenAIRE

    Ji, Xincai; Saha, Sucharita; Martin, Gilles E.

    2015-01-01

    It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different informatio...

  15. Expression of long-term plasticity at individual synapses in hippocampus is graded, bidirectional, and mainly presynaptic: optical quantal analysis.

    Science.gov (United States)

    Enoki, Ryosuke; Hu, Yi-Ling; Hamilton, David; Fine, Alan

    2009-04-30

    Key aspects of the expression of long-term potentiation (LTP) and long-term depression (LTD) remain unresolved despite decades of investigation. Alterations in postsynaptic glutamate receptors are believed to contribute to the expression of various forms of LTP and LTD, but the relative importance of presynaptic mechanisms is controversial. In addition, while aggregate synaptic input to a cell can undergo sequential and graded (incremental) LTP and LTD, it has been suggested that individual synapses may only support binary changes between initial and modified levels of strength. We have addressed these issues by combining electrophysiological methods with two-photon optical quantal analysis of plasticity at individual active (non-silent) Schaffer collateral synapses on CA1 pyramidal neurons in acute slices of hippocampus from adolescent rats. We find that these synapses sustain graded, bidirectional long-term plasticity. Remarkably, changes in potency are small and insignificant; long-term plasticity at these synapses is expressed overwhelmingly via presynaptic changes in reliability of transmitter release.

  16. Fear Extinction as a Model for Synaptic Plasticity in Major Depressive Disorder

    OpenAIRE

    Marion Kuhn; Nora Höger; Bernd Feige; Jens Blechert; Claus Normann; Christoph Nissen

    2014-01-01

    BACKGROUND: The neuroplasticity hypothesis of major depressive disorder proposes that a dysfunction of synaptic plasticity represents a basic pathomechanism of the disorder. Animal models of depression indicate enhanced plasticity in a ventral emotional network, comprising the amygdala. Here, we investigated fear extinction learning as a non-invasive probe for amygdala-dependent synaptic plasticity in patients with major depressive disorder and healthy controls. METHODS: Differential fear con...

  17. A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Takashi Nakano

    2010-02-01

    Full Text Available Corticostriatal synapse plasticity of medium spiny neurons is regulated by glutamate input from the cortex and dopamine input from the substantia nigra. While cortical stimulation alone results in long-term depression (LTD, the combination with dopamine switches LTD to long-term potentiation (LTP, which is known as dopamine-dependent plasticity. LTP is also induced by cortical stimulation in magnesium-free solution, which leads to massive calcium influx through NMDA-type receptors and is regarded as calcium-dependent plasticity. Signaling cascades in the corticostriatal spines are currently under investigation. However, because of the existence of multiple excitatory and inhibitory pathways with loops, the mechanisms regulating the two types of plasticity remain poorly understood. A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32, as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA, protein phosphatase 2A (PP2A, and the phosphorylation site at threonine 75 of DARPP-32 (Thr75 served as the major switch for inducing LTD and LTP. Calcium input modulated this loop through the PP2B (phosphatase 2B-CK1 (casein kinase 1-Cdk5 (cyclin-dependent kinase 5-Thr75 pathway and PP2A, whereas calcium and dopamine input activated the loop via PKA activation by cyclic AMP (cAMP. The positive feedback loop displayed robust bi-stable responses following changes in the reaction parameters. Increased basal dopamine levels disrupted this dopamine-dependent plasticity. The

  18. Regulation of hippocampal synaptic plasticity thresholds and changes in exploratory and learning behavior in dominant negative NPR-B mutant rats

    Directory of Open Access Journals (Sweden)

    Gleb eBarmashenko

    2014-12-01

    Full Text Available The second messenger cyclic GMP affects synaptic transmission and modulates synaptic plasticity and certain types of learning and memory processes. The impact of the natriuretic peptide receptor B (NPR-B and its ligand C-type natriuretic peptide (CNP, one of several cGMP producing signalling systems, on hippocampal synaptic plasticity and learning is, however, less well understood. We have previously shown that the NPR-B ligand CNP increases the magnitude of long-term depression (LTD in hippocampal area CA1, while reducing the induction of long-term potentiation (LTP. We have extended this line of research to show that bidirectional plasticity is affected in the opposite way in rats expressing a dominant-negative mutant of NPR-B (NSE-NPR-BdeltaKC lacking the intracellular guanylyl cyclase domain under control of a promoter for neuron-specific enolase. The brain cells of these transgenic rats express functional dimers of the NPR-B receptor containing the dominant-negative NPR-BdeltaKC mutant, and therefore show decreased CNP-stimulated cGMP-production in brain membranes. The NPR-B transgenic rats display enhanced LTP but reduced LTD in hippocampal slices. When the frequency-dependence of synaptic modification to afferent stimulation in the range of 1-100 Hz was assessed in transgenic rats the threshold for LTP induction was raised, but LTD induction was facilitated. In parallel, NPR-BdeltaKC rats exhibited an enhancement in exploratory and learning behavior. These results indicate that bidirectional plasticity and learning and memory mechanism are affected in transgenic rats expressing a dominant-negative mutant of NPR-B. Our data substantiate the hypothesis that NPR-B-dependent cGMP signalling has a modulatory role for synaptic information storage and learning.

  19. On higher order computations and synaptic meta-plasticity in the human brain: IT point of view (March, 2016)

    OpenAIRE

    Ambroszkiewicz, Stanislaw

    2016-01-01

    Glia modify neuronal connectivity by creating structural changes in the neuronal connectome. Glia also influence the functional connectome by modifying the flow of information through neural networks (Fields et al. 2015). There are strong experimental evidences that glia are responsible for synaptic meta-plasticity. Synaptic plasticity is the modification of the strength of connections between neurons. Meta-plasticity, i.e. plasticity of synaptic plasticity, may be viewed as mechanisms for dy...

  20. BAI1 regulates spatial learning and synaptic plasticity in the hippocampus

    DEFF Research Database (Denmark)

    Zhu, Dan; Li, Chenchen; Swanson, Andrew M;

    2015-01-01

    Synaptic plasticity is the ability of synapses to modulate the strength of neuronal connections; however, the molecular factors that regulate this feature are incompletely understood. Here, we demonstrated that mice lacking brain-specific angiogenesis inhibitor 1 (BAI1) have severe deficits...... of PSD-95 expression in hippocampal neurons in BAI1-deficient mice by viral gene therapy was sufficient to compensate for Bai1 loss and rescued deficits in synaptic plasticity. Together, our results reveal that interaction of BAI1 with MDM2 in the brain modulates PSD-95 levels and thereby regulates...... synaptic plasticity. Moreover, these results suggest that targeting this pathway has therapeutic potential for a variety of neurological disorders....

  1. Inhibitory synaptic plasticity: spike timing-dependence and putative network function

    OpenAIRE

    Vogels, Tim P.; Froemke, Robert C.; Nicolas Doyon; Matthieu Gilson; Haas, Julie S.; Robert Liu; Arianna Maffei; Paul Miller; Corette Wierenga; Woodin, Melanie A.; Henning Sprekeler

    2013-01-01

    While the plasticity of excitatory synaptic connections in the brain has been widely studied, the plasticity of inhibitory connections is much less understood. Here, we present recent experimental and theoretical findings concerning the rules of spike timing-dependent inhibitory plasticity and their putative network function. This is a summary of a workshop at the COSYNE conference 2012.

  2. The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens.

    Science.gov (United States)

    Ji, Xincai; Saha, Sucharita; Martin, Gilles E

    2015-01-01

    It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive). Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD) and long-term potentiation (LTP) and long-term potentiation (tLTP) and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength. PMID:26257641

  3. Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia

    OpenAIRE

    Crabtree, Gregg W.; Gogos, Joseph A.

    2014-01-01

    Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adapt...

  4. Cross-talk induces bifurcations in nonlinear models of synaptic plasticity.

    Science.gov (United States)

    Elliott, Terry

    2012-02-01

    Linear models of synaptic plasticity provide a useful starting-point for examining the dynamics of neuronal development and learning, but their inherent problems are well known. Models of synaptic plasticity that embrace the demands of biological realism are therefore typically nonlinear. Viewed from a more abstract perspective, nonlinear models of synaptic plasticity are a subset of nonlinear dynamical systems. As such, they may therefore exhibit bifurcations under the variation of control parameters, including noise and errors in synaptic updates. One source of noise or error is the cross-talk that occurs during otherwise Hebbian plasticity. Under cross-talk, stimulation of a set of synapses can induce or modify plasticity in adjacent, unstimulated synapses. Here, we analyze two nonlinear models of developmental synaptic plasticity and a model of independent component analysis in the presence of a simple model of cross-talk. We show that cross-talk does indeed induce bifurcations in these models, entirely destroying their ability to acquire either developmentally or learning-related patterns of fixed points. Importantly, the critical level of cross-talk required to induce bifurcations in these models is very sensitive to the statistics of the afferents' activities and the number of afferents synapsing on a postsynaptic cell. In particular, the critical level can be made arbitrarily small. Because bifurcations are inevitable in nonlinear models, our results likely apply to many nonlinear models of synaptic plasticity, although the precise details vary by model. Hence, many nonlinear models of synaptic plasticity are potentially fatally compromised by the toxic influence of cross-talk and other sources of noise and errors more generally. We conclude by arguing that biologically realistic models of synaptic plasticity must be robust against noise-induced bifurcations and that biological systems may have evolved strategies to circumvent their possible dangers.

  5. Bidirectional Plasticity in Striatonigral Synapses: A Switch to Balance Direct and Indirect Basal Ganglia Pathways

    Science.gov (United States)

    Aceves, Jose J.; Rueda-Orozco, Pavel E.; Hernandez-Martinez, Ricardo; Galarraga, Elvira; Bargas, Jose

    2011-01-01

    There is no hypothesis to explain how direct and indirect basal ganglia (BG) pathways interact to reach a balance during the learning of motor procedures. Both pathways converge in the substantia nigra pars reticulata (SNr) carrying the result of striatal processing. Unfortunately, the mechanisms that regulate synaptic plasticity in striatonigral…

  6. NMDA receptor subunit composition determines the polarity of leptin-induced synaptic plasticity

    OpenAIRE

    Moult, Peter R; Harvey, Jenni

    2011-01-01

    Leptin is a hormone that crosses the blood-brain barrier and regulates numerous CNS functions. The hippocampus in particular is an important site for leptin action. Indeed, leptin markedly influences excitatory synaptic transmission and synaptic plasticity in this brain region. Recent studies indicate that leptin modulation of hippocampal excitatory synaptic transmission is age-dependent however the cellular basis for this is unclear. Here we show that early in development leptin evokes a tra...

  7. A role for synaptic plasticity in the adolescent development of executive function

    OpenAIRE

    Selemon, L D

    2013-01-01

    Adolescent brain maturation is characterized by the emergence of executive function mediated by the prefrontal cortex, e.g., goal planning, inhibition of impulsive behavior and set shifting. Synaptic pruning of excitatory contacts is the signature morphologic event of late brain maturation during adolescence. Mounting evidence suggests that glutamate receptor-mediated synaptic plasticity, in particular long term depression (LTD), is important for elimination of synaptic contacts in brain deve...

  8. Effects of changes in glucose concentration on synaptic plasticity in hippocampal slices

    NARCIS (Netherlands)

    Gispen, W.H.; Kamal, A.; Spoelstra, K.; Biessels, G.J.; Urban, I.J.A.

    1999-01-01

    The effects of a low or high concentration of glucose in the perfusion medium on synaptic activity and plasticity were studied in hippocampal slices from rats. Low-glucose medium depressed the field excitatory post-synaptic potentials (fEPSP) significantly, whereas high-glucose medium had little eff

  9. Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation

    OpenAIRE

    Adasme, Tatiana; Haeger, Paola; Paula-Lima, Andrea C.; Espinoza, Italo; Casas-Alarcón, M. Mercedes; Carrasco, M. Angélica; Hidalgo, Cecilia

    2011-01-01

    Ryanodine receptors (RyR) amplify activity-dependent calcium influx via calcium-induced calcium release. Calcium signals trigger postsynaptic pathways in hippocampal neurons that underlie synaptic plasticity, learning, and memory. Recent evidence supports a role of the RyR2 and RyR3 isoforms in these processes. Along with calcium signals, brain-derived neurotrophic factor (BDNF) is a key signaling molecule for hippocampal synaptic plasticity and spatial memory. Upon binding to specific TrkB r...

  10. AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging

    OpenAIRE

    Henley JM; Wilkinson KA

    2013-01-01

    Even in healthy individuals there is an inexorable agerelated decline in cognitive function. This is due, in large part, to reduced synaptic plasticity caused by changes in the molecular composition of the postsynaptic membrane. AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate the overwhelming majority of fast excitatory transmission in the brain. Changes in AMPAR number and/or function are a core feature of synaptic plasticity and age-related cognitive decline, AMPARs...

  11. Emotional enhancement of memory: how norepinephrine enables synaptic plasticity

    OpenAIRE

    Tully Keith; Bolshakov Vadim Y

    2010-01-01

    Abstract Changes in synaptic strength are believed to underlie learning and memory. We explore the idea that norepinephrine is an essential modulator of memory through its ability to regulate synaptic mechanisms. Emotional arousal leads to activation of the locus coeruleus with the subsequent release of norepineprine in the brain, resulting in the enhancement of memory. Norepinephrine activates both pre- and post-synaptic adrenergic receptors at central synapses with different functional outc...

  12. Reversible plasticity of fear memory-encoding amygdala synaptic circuits even after fear memory consolidation.

    Directory of Open Access Journals (Sweden)

    Ingie Hong

    Full Text Available It is generally believed that after memory consolidation, memory-encoding synaptic circuits are persistently modified and become less plastic. This, however, may hinder the remaining capacity of information storage in a given neural circuit. Here we consider the hypothesis that memory-encoding synaptic circuits still retain reversible plasticity even after memory consolidation. To test this, we employed a protocol of auditory fear conditioning which recruited the vast majority of the thalamic input synaptic circuit to the lateral amygdala (T-LA synaptic circuit; a storage site for fear memory with fear conditioning-induced synaptic plasticity. Subsequently the fear memory-encoding synaptic circuits were challenged with fear extinction and re-conditioning to determine whether these circuits exhibit reversible plasticity. We found that fear memory-encoding T-LA synaptic circuit exhibited dynamic efficacy changes in tight correlation with fear memory strength even after fear memory consolidation. Initial conditioning or re-conditioning brought T-LA synaptic circuit near the ceiling of their modification range (occluding LTP and enhancing depotentiation in brain slices prepared from conditioned or re-conditioned rats, while extinction reversed this change (reinstating LTP and occluding depotentiation in brain slices prepared from extinguished rats. Consistently, fear conditioning-induced synaptic potentiation at T-LA synapses was functionally reversed by extinction and reinstated by subsequent re-conditioning. These results suggest reversible plasticity of fear memory-encoding circuits even after fear memory consolidation. This reversible plasticity of memory-encoding synapses may be involved in updating the contents of original memory even after memory consolidation.

  13. Synaptic plasticity, AMPA-R trafficking, and Ras-MAPK signaling

    Institute of Scientific and Technical Information of China (English)

    Yun GU; Ruth L STORNETTA

    2007-01-01

    Synaptic modification of transmission is a general phenomenon expressed at al-most every excitatory synapse in the mammalian brain. Over the last three decades,much has been discovered about the cellular, synaptic, molecular, and signalingmechanisms responsible for controlling synaptic transmission and plasticity. Here,we present a brief review of these mechanisms with emphasis on the currentunderstanding of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid recep-tor (AMPA-R) trafficking and Ras-mitogen-activated protein kinase (MAPK)signaling events involved in controlling synaptic transmission.

  14. Axonal accumulation of synaptic markers in APP transgenic Drosophila depends on the NPTY motif and is paralleled by defects in synaptic plasticity

    DEFF Research Database (Denmark)

    Rusu, Patricia; Jansen, Anna; Soba, Peter;

    2007-01-01

    neurotransmission at the neuromuscular junction in transgenic larvae that express human APP. Consistent with the observation that these larvae do not show any obvious movement deficits, we found no changes in basal synaptic transmission. However, short-term synaptic plasticity was affected by overexpression of APP....... Together, our results show that overexpression of APP induces partial stalling of axonal transport vesicles, paralleled by abnormalities in synaptic plasticity, which may provide a functional link to the deterioration of cognitive functions observed in AD....

  15. Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome.

    Science.gov (United States)

    Hethorn, Whitney R; Ciarlone, Stephanie L; Filonova, Irina; Rogers, Justin T; Aguirre, Daniela; Ramirez, Raquel A; Grieco, Joseph C; Peters, Melinda M; Gulick, Danielle; Anderson, Anne E; L Banko, Jessica; Lussier, April L; Weeber, Edwin J

    2015-05-01

    The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain. PMID:25864922

  16. Activity-dependent synaptic plasticity modulates the critical phase of brain development.

    Science.gov (United States)

    Chaudhury, Sraboni; Sharma, Vikram; Kumar, Vivek; Nag, Tapas C; Wadhwa, Shashi

    2016-04-01

    Plasticity or neuronal plasticity is a unique and adaptive feature of nervous system which allows neurons to reorganize their interactions in response to an intrinsic or extrinsic stimulation and shapes the formation and maintenance of a functional neuronal circuit. Synaptic plasticity is the most important form of neural plasticity and plays critical role during the development allowing the formation of precise neural connectivity via the process of pruning. In the sensory systems-auditory and visual, this process is heavily dependent on the external cues perceived during the development. Environmental enrichment paradigms in an activity-dependent manner result in early maturation of the synapses and more efficient trans-synaptic signaling or communication flow. This has been extensively observed in the avian auditory system. On the other hand, stimuli results in negative effect can cause alterations in the synaptic connectivity and strength resulting in various developmental brain disorders including autism, fragile X syndrome and rett syndrome. In this review we discuss the role of different forms of activity (spontaneous or environmental) during the development of the nervous system in modifying synaptic plasticity necessary for shaping the adult brain. Also, we try to explore various factors (molecular, genetic and epigenetic) involved in altering the synaptic plasticity in positive and negative way. PMID:26515724

  17. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain

    Directory of Open Access Journals (Sweden)

    Christian Bonansco

    2016-01-01

    Full Text Available Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks.

  18. Plasticity of Hippocampal Excitatory-Inhibitory Balance: Missing the Synaptic Control in the Epileptic Brain.

    Science.gov (United States)

    Bonansco, Christian; Fuenzalida, Marco

    2016-01-01

    Synaptic plasticity is the capacity generated by experience to modify the neural function and, thereby, adapt our behaviour. Long-term plasticity of glutamatergic and GABAergic transmission occurs in a concerted manner, finely adjusting the excitatory-inhibitory (E/I) balance. Imbalances of E/I function are related to several neurological diseases including epilepsy. Several evidences have demonstrated that astrocytes are able to control the synaptic plasticity, with astrocytes being active partners in synaptic physiology and E/I balance. Here, we revise molecular evidences showing the epileptic stage as an abnormal form of long-term brain plasticity and propose the possible participation of astrocytes to the abnormal increase of glutamatergic and decrease of GABAergic neurotransmission in epileptic networks. PMID:27006834

  19. Phosphorylation of AMPA receptors is required for sensory deprivation-induced homeostatic synaptic plasticity.

    Science.gov (United States)

    Goel, Anubhuti; Xu, Linda W; Snyder, Kevin P; Song, Lihua; Goenaga-Vazquez, Yamila; Megill, Andrea; Takamiya, Kogo; Huganir, Richard L; Lee, Hey-Kyoung

    2011-01-01

    Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca(2+)-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

  20. Phosphorylation of AMPA receptors is required for sensory deprivation-induced homeostatic synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Anubhuti Goel

    Full Text Available Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca(2+-permeable AMPA receptors (CP-AMPARs. However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1 subunit at the serine 845 (S845 site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants, which is a substrate of cAMP-dependent kinase (PKA, show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.

  1. Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels.

    Science.gov (United States)

    Schreiber, Joerg; Végh, Marlene J; Dawitz, Julia; Kroon, Tim; Loos, Maarten; Labonté, Dorthe; Li, Ka Wan; Van Nierop, Pim; Van Diepen, Michiel T; De Zeeuw, Chris I; Kneussel, Matthias; Meredith, Rhiannon M; Smit, August B; Van Kesteren, Ronald E

    2015-11-01

    Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two actin isoforms, β- and γ-actin, are expressed in dendritic spines, the specific contribution of γ-actin in the expression of synaptic plasticity is unknown. We show that synaptic γ-actin levels are regulated by the E3 ubiquitin ligase TRIM3. TRIM3 protein and Actg1 transcript are colocalized in messenger ribonucleoprotein granules responsible for the dendritic targeting of messenger RNAs. TRIM3 polyubiquitylates γ-actin, most likely cotranslationally at synaptic sites. Trim3(-/-) mice consequently have increased levels of γ-actin at hippocampal synapses, resulting in higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory consolidation. Interestingly, hippocampal deletion of Actg1 caused an increase in long-term fear memory. Collectively, our findings suggest that temporal control of γ-actin levels by TRIM3 is required to regulate the timing of hippocampal plasticity. We propose a model in which TRIM3 regulates synaptic γ-actin turnover and actin filament stability and thus forms a transient inhibitory constraint on the expression of hippocampal synaptic plasticity. PMID:26527743

  2. CaMKII Activity in the Ventral Tegmental Area Gates Cocaine-Induced Synaptic Plasticity in the Nucleus Accumbens

    OpenAIRE

    Liu, Xiaojie; Liu, Yong; Zhong, Peng; Wilkinson, Brianna; Qi, Jinshun; Olsen, Christopher M; Bayer, K. Ulrich; Liu, Qing-song

    2013-01-01

    Addictive drugs such as cocaine induce synaptic plasticity in discrete regions of the reward circuit. The aim of the present study is to investigate whether cocaine-evoked synaptic plasticity in the ventral tegmental area (VTA) and nucleus accumbens (NAc) is causally linked. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of long-term synaptic plasticity, learning, and drug addiction. We examined whether blocking CaMKII activity in the VTA affected cocaine conditio...

  3. Downregulation of caveolin-1 contributes to the synaptic plasticity deficit in the hippocampus of aged rats*******

    Institute of Scientific and Technical Information of China (English)

    Yang Liu; Zhanhua Liang; Jing Liu; Wei Zou; Xiaoyan Li; Yachen Wang; Lijia An

    2013-01-01

    Caveolin-1 is involved in the regulation of synaptic plasticity, but the relationship between its pression and cognitive function during aging remains controversial. To explore the relationship be-tween synaptic plasticity in the aging process and changes in learning and memory, we examined caveolin-1 expression in the hippocampus, cortex and cerebel um of rats at different ages. We also examined the relationship between the expression of caveolin-1 and synaptophysin, a marker of synaptic plasticity. Hippocampal caveolin-1 and synaptophysin expression in aged (22-24 month old) rats was significantly lower than that in young (1 month old) and adult (4 months old) rats. pression levels of both proteins were significantly greater in the cortex of aged rats than in that of young or adult rats, and levels were similar between the three age groups in the cerebel um. Linear regression analysis revealed that hippocampal expression of synaptophysin was associated with memory and learning abilities. Moreover, synaptophysin expression correlated positively with caveolin-1 expression in the hippocampus, cortex and cerebel um. These results confirm that caveolin-1 has a regulatory effect on synaptic plasticity, and suggest that the downregulation of hippocampal caveolin-1 expression causes a decrease in synaptic plasticity during physiological aging.

  4. Plasticity of inhibitory synaptic network interactions in the lateral amygdala upon fear conditioning in mice.

    Science.gov (United States)

    Szinyei, Csaba; Narayanan, Rajeevan T; Pape, Hans-Christian

    2007-02-01

    After fear conditioning, plastic changes of excitatory synaptic transmission occur in the amygdala. Fear-related memory also involves the GABAergic system, although no influence on inhibitory synaptic transmission is known. In the present study we assessed the influence of Pavlovian fear conditioning on the plasticity of GABAergic synaptic interactions in the lateral amygdala (LA) in brain slices prepared from fear-conditioned, pseudo-trained and naïve adult mice. Theta-burst tetanization of thalamic afferent inputs to the LA evoked an input-specific potentiation of inhibitory postsynaptic responses in projection neurons; the cortical input was unaffected. Philanthotoxin (10 microM), an antagonist of Ca2+-permeable AMPA receptors, disabled this plastic phenomenon. Surgical isolation of the LA, extracellular application of a GABA(B) receptor antagonist (CGP 55845A, 10 microM) or an NMDA receptor antagonist (APV, 50 microM), or intracellular application of BAPTA (10 mM), did not influence the plasticity. The plasticity also showed as a potentiation of monosynaptic excitatory responses in putative GABAergic interneurons. Pavlovian fear conditioning, but not pseudo-conditioning, resulted in a significant reduction in this potentiation that was evident 24 h after training. Two weeks after training, the potentiation returned to control levels. In conclusion, a reduction in potentiation of inhibitory synaptic interactions occurs in the LA and may contribute to a shift in synaptic balance towards excitatory signal flow during the processes of fear-memory acquisition or consolidation.

  5. Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus.

    Science.gov (United States)

    Broussard, John I; Yang, Kechun; Levine, Amber T; Tsetsenis, Theodoros; Jenson, Daniel; Cao, Fei; Garcia, Isabella; Arenkiel, Benjamin R; Zhou, Fu-Ming; De Biasi, Mariella; Dani, John A

    2016-03-01

    Dopamine release during reward-driven behaviors influences synaptic plasticity. However, dopamine innervation and release in the hippocampus and its role during aversive behaviors are controversial. Here, we show that in vivo hippocampal synaptic plasticity in the CA3-CA1 circuit underlies contextual learning during inhibitory avoidance (IA) training. Immunohistochemistry and molecular techniques verified sparse dopaminergic innervation of the hippocampus from the midbrain. The long-term synaptic potentiation (LTP) underlying the learning of IA was assessed with a D1-like dopamine receptor agonist or antagonist in ex vivo hippocampal slices and in vivo in freely moving mice. Inhibition of D1-like dopamine receptors impaired memory of the IA task and prevented the training-induced enhancement of both ex vivo and in vivo LTP induction. The results indicate that dopamine-receptor signaling during an aversive contextual task regulates aversive memory retention and regulates associated synaptic mechanisms in the hippocampus that likely underlie learning. PMID:26904943

  6. SYNAPTIC PLASTICITY IN THE DENTATE GYRUS OF AGED RATS IS ALTERED AFTER CHRONIC NIMODIPINE APPLICATION

    OpenAIRE

    deJong, GI; Buwalda, B.; Schuurman, T.; Luiten, PGM

    1992-01-01

    We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this compound improves hippocampal neuronal physiology and enhances cognitive function during aging. In the supragranular layer of the dentate gyrus we found a 24% decrease in synaptic density (Nv) in a...

  7. Regulation of Synaptic Transmission and Plasticity by Neuronal Nicotinic Acetylcholine Receptors

    OpenAIRE

    McKay, Bruce E.; Placzek, Andon N; Dani, John A.

    2007-01-01

    Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the central nervous system and participate in a variety of physiological functions. Recent advances have revealed roles of nAChRs in the regulation of synaptic transmission and synaptic plasticity, particularly in the hippocampus and midbrain dopamine centers. In general, activation of nAChRs causes membrane depolarization and directly and indirectly increases the intracellular calcium concentration. Thus, when nAChRs ...

  8. Hippocampal Place Cell Firing Patterns can Induce Long-Term Synaptic Plasticity In Vitro

    OpenAIRE

    Isaac, John T. R.; Buchanan, Katherine A.; Muller, Robert U.; Mellor, Jack R.

    2009-01-01

    In the hippocampus, synaptic strength between pyramidal cells is modifiable by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD), both of which require coincident pre- and postsynaptic activity. In vivo, many pyramidal cells exhibit location-specific activity patterns and are known as “place cells”. The combination of these factors suggests that synaptic plasticity will be induced at synapses connecting place cells with overlapping firing fields, sinc...

  9. A neuromorphic implementation of multiple spike-timing synaptic plasticity rules for large-scale neural networks

    Directory of Open Access Journals (Sweden)

    Runchun Mark Wang

    2015-05-01

    Full Text Available 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 2^26 (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 and/or delayed pre-synaptic spike to the target synapse 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 2^36 (64G synaptic adaptors on a current high-end FPGA platform.

  10. Synaptic plasticity, neural circuits and the emerging role of altered short-term information processing in schizophrenia

    Directory of Open Access Journals (Sweden)

    Gregg W. Crabtree

    2014-11-01

    Full Text Available Synaptic plasticity alters the strength of information flow between presynaptic and postsynaptic neurons and thus modifies the likelihood that action potentials in a presynaptic neuron will lead to an action potential in a postsynaptic neuron. As such, synaptic plasticity and pathological changes in synaptic plasticity impact the synaptic computation which controls the information flow through the neural microcircuits responsible for the complex information processing necessary to drive adaptive behaviors. As current theories of neuropsychiatric disease suggest that distinct dysfunctions in neural circuit performance may critically underlie the unique symptoms of these diseases, pathological alterations in synaptic plasticity mechanisms may be fundamental to the disease process. Here we consider mechanisms of both short-term and long-term plasticity of synaptic transmission and their possible roles in information processing by neural microcircuits in both health and disease. As paradigms of neuropsychiatric diseases with strongly implicated risk genes, we discuss the findings in schizophrenia and autism and consider the alterations in synaptic plasticity and network function observed in both human studies and genetic mouse models of these diseases. Together these studies have begun to point towards a likely dominant role of short-term synaptic plasticity alterations in schizophrenia while dysfunction in autism spectrum disorders may be due to a combination of both short-term and long-term synaptic plasticity alterations.

  11. The requirement of BDNF for hippocampal synaptic plasticity is experience‐dependent

    Science.gov (United States)

    Aarse, Janna; Herlitze, Stefan

    2016-01-01

    ABSTRACT Brain‐derived neurotrophic factor (BDNF) supports neuronal survival, growth, and differentiation and has been implicated in forms of hippocampus‐dependent learning. In vitro, a specific role in hippocampal synaptic plasticity has been described, although not all experience‐dependent forms of synaptic plasticity critically depend on BDNF. Synaptic plasticity is likely to enable long‐term synaptic information storage and memory, and the induction of persistent (>24 h) forms, such as long‐term potentiation (LTP) and long‐term depression (LTD) is tightly associated with learning specific aspects of a spatial representation. Whether BDNF is required for persistent (>24 h) forms of LTP and LTD, and how it contributes to synaptic plasticity in the freely behaving rodent has never been explored. We examined LTP, LTD, and related forms of learning in the CA1 region of freely dependent mice that have a partial knockdown of BDNF (BDNF+/−). We show that whereas early‐LTD (BDNF, short‐term depression (BDNF is required for LTP that is induced by mild, but not strong short afferent stimulation protocols. Object‐place learning triggers LTD in the CA1 region of mice. We observed that object‐place memory was impaired and the object‐place exploration failed to induce LTD in BDNF+/− mice. Furthermore, spatial reference memory, that is believed to be enabled by LTP, was also impaired. Taken together, these data indicate that BDNF is required for specific, but not all, forms of hippocampal‐dependent information storage and memory. Thus, very robust forms of synaptic plasticity may circumvent the need for BDNF, rather it may play a specific role in the optimization of weaker forms of plasticity. The finding that both learning‐facilitated LTD and spatial reference memory are both impaired in BDNF+/− mice, suggests moreover, that it is critically required for the physiological encoding of hippocampus‐dependent memory. © 2015 The Authors

  12. Synaptic plasticity in the hippocampal area CA1-subiculum projection: implications for theories of memory.

    Science.gov (United States)

    O'Mara, S M; Commins, S; Anderson, M

    2000-01-01

    This paper reviews investigations of synaptic plasticity in the major, and underexplored, pathway from hippocampal area CA1 to the subiculum. This brain area is the major synaptic relay for the majority of hippocampal area CA1 neurons, making the subiculum the last relay of the hippocampal formation prior to the cortex. The subiculum thus has a very major role in mediating hippocampal-cortical interactions. We demonstrate that the projection from hippocampal area CA1 to the subiculum sustains plasticity on a number of levels. We show that this pathway is capable of undergoing both long-term potentiation (LTP) and paired-pulse facilitation (PPF, a short-term plastic effect). Although we failed to induce long-term depression (LTD) of this pathway with low-frequency stimulation (LFS) and two-pulse stimulation (TPS), both protocols can induce a "late-developing" potentiation of synaptic transmission. We further demonstrate that baseline synaptic transmission can be dissociated from paired-pulse stimulation of the same pathway; we also show that it is possible, using appropriate protocols, to change PPF to paired-pulse depression, thus revealing subtle and previously undescribed mechanisms which regulate short-term synaptic plasticity. Finally, we successfully recorded from individual subicular units in the freely-moving animal, and provide a description of the characteristics of such neurons in a pellet-chasing task. We discuss the implications of these findings in relation to theories of the biological consolidation of memory.

  13. Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity

    NARCIS (Netherlands)

    J. Jaworski; L.C. Kapitein; S. Montenegro Gouveia; B.R. Dortland; P.S. Wulf; I. Grigoriev; P. Camera; S.A. Spangler; P. Di Stefano; J. Demmers; H. Krugers; P. Defilippi; A. Akhmanova; C.C. Hoogenraad

    2009-01-01

    Dendritic spines are the major sites of excitatory synaptic input, and their morphological changes have been linked to learning and memory processes. Here, we report that growing microtubule plus ends decorated by the microtubule tip-tracking protein EB3 enter spines and can modulate spine morpholog

  14. Astroglial calcium signaling displays short-term plasticity and adjusts synaptic efficacy

    Directory of Open Access Journals (Sweden)

    Jeremie eSibille

    2015-05-01

    Full Text Available Astrocytes are dynamic signaling brain elements able to sense neuronal inputs and to respond by complex calcium signals, which are thought to represent their excitability. Such signaling has been proposed to modulate, or not, neuronal activities ranging from basal synaptic transmission to epileptiform discharges. However, whether calcium signaling in astrocytes exhibits activity-dependent changes and acutely modulates short-term synaptic plasticity is currently unclear. We here show, using dual recordings of astroglial calcium signals and synaptic transmission, that calcium signaling in astrocytes displays, concomitantly to excitatory synapses, short-term plasticity in response to prolonged repetitive and tetanic stimulations of Schaffer collaterals. We also found that acute inhibition of calcium signaling in astrocytes by intracellular calcium chelation rapidly potentiates excitatory synaptic transmission and short-term plasticity of Shaffer collateral CA1 synapses, i.e. paired-pulse facilitation and responses to tetanic and prolonged repetitive stimulation. These data reveal that calcium signaling of astrocytes is plastic and down-regulates basal transmission and short-term plasticity of hippocampal CA1 glutamatergic synapses.

  15. Hippocampal testosterone relates to reference memory performance and synaptic plasticity in male rats

    Directory of Open Access Journals (Sweden)

    Kristina eSchulz

    2010-12-01

    Full Text Available Steroids are important neuromodulators influencing cognitive performance and synaptic plasticity. While the majority of literature concerns adrenal- and gonadectomized animals, very little is known about the natural endogenous release of hormones during learning. Therefore, we measured blood and brain (hippocampus, prefrontal cortex testosterone, estradiol, and corticosterone concentrations of intact male rats undergoing a spatial learning paradigm which is known to reinforce hippocampal plasticity. We found significant modulations of all investigated hormones over the training course. Corticosterone and testosterone were correlated manifold with behaviour, while estradiol expressed fewer correlations. In the recall session, testosterone was tightly coupled to reference memory performance, which is crucial for reinforcement of synaptic plasticity in the dentate gyrus. Intriguingly, prefrontal cortex and hippocampal levels related differentially to reference memory performance. Correlations of testosterone and corticosterone switched from unspecific activity to specific cognitive functions over training. Correspondingly, exogenous application of testosterone revealed different effects on synaptic and neuronal plasticity in trained versus untrained animals. While hippocampal long-term potentiation (LTP of the field excitatory postsynaptic potential (fEPSP was prolonged in untrained rats, both the fEPSP- and the population spike amplitude-LTP was impaired in trained rats. Behavioural performance was unaffected, but correlations of hippocampal field potentials with behaviour were decoupled in treated rats. The data provide important evidence that besides adrenal, also gonadal steroids play a mechanistic role in linking synaptic plasticity to cognitive performance.

  16. Learning Structure of Sensory Inputs with Synaptic Plasticity Leads to Interference

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    Joseph eChrol-Cannon

    2015-08-01

    Full Text Available Synaptic plasticity is often explored as a form of unsupervised adaptationin cortical microcircuits to learn the structure of complex sensoryinputs and thereby improve performance of classification and prediction. The question of whether the specific structure of the input patterns is encoded in the structure of neural networks has been largely neglected. Existing studies that have analyzed input-specific structural adaptation have used simplified, synthetic inputs in contrast to complex and noisy patterns found in real-world sensory data.In this work, input-specific structural changes are analyzed forthree empirically derived models of plasticity applied to three temporal sensory classification tasks that include complex, real-world visual and auditory data. Two forms of spike-timing dependent plasticity (STDP and the Bienenstock-Cooper-Munro (BCM plasticity rule are used to adapt the recurrent network structure during the training process before performance is tested on the pattern recognition tasks.It is shown that synaptic adaptation is highly sensitive to specific classes of input pattern. However, plasticity does not improve the performance on sensory pattern recognition tasks, partly due to synaptic interference between consecutively presented input samples. The changes in synaptic strength produced by one stimulus are reversed by thepresentation of another, thus largely preventing input-specific synaptic changes from being retained in the structure of the network.To solve the problem of interference, we suggest that models of plasticitybe extended to restrict neural activity and synaptic modification to a subset of the neural circuit, which is increasingly found to be the casein experimental neuroscience.

  17. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    Science.gov (United States)

    Oliva, Carolina A.; Vargas, Jessica Y.; Inestrosa, Nibaldo C.

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer’s disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts. PMID:24348327

  18. Region-specific restoration of striatal synaptic plasticity by dopamine grafts in experimental parkinsonism

    OpenAIRE

    Rylander, D.; Bagetta, V.; Pendolino, V.; Zianni, E.; S. Grealish; Gardoni, F.; DI LUCA M; P. Calabresi; Cenci, M. A.; Picconi, B.

    2013-01-01

    This paper identifies long-term synaptic plasticity restoration as an underlying mechanism of progressive motor improvement after neuronal transplantation in a rat Parkinson model. A Parkinson-associated loss of plasticity in the host striatum could be restored by transplanted dopamine neurons with sufficient fiber innervation, suggesting that functional innervation with possible synapse formation is required for the long-term effect of neural transplants. These data support a multisite-graft...

  19. Long-Term Exercise Is Needed to Enhance Synaptic Plasticity in the Hippocampus

    Science.gov (United States)

    Patten, Anna R.; Sickmann, Helle; Hryciw, Brett N.; Kucharsky, Tessa; Parton, Roberta; Kernick, Aimee; Christie, Brian R.

    2013-01-01

    Exercise can have many benefits for the body, but it also benefits the brain by increasing neurogenesis, synaptic plasticity, and performance on learning and memory tasks. The period of exercise needed to realize the structural and functional benefits for the brain have not been well delineated, and previous studies have used periods of exercise…

  20. Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Amit Agarwal

    2014-08-01

    Full Text Available Neuregulin-1 (NRG1 gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an “optimal” level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect.

  1. SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala

    Science.gov (United States)

    Sinai, Laleh; Duffy, Steven; Roder, John C.

    2010-01-01

    The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src…

  2. Water maze learning and hippocampal synaptic plasticity in streptozotocin diabetic rats: effects of insulin treatment

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.; Kamal, A.; Urban, I.J.A.; Spruijt, B.M.; Erkelens, D.W.

    1998-01-01

    Streptozotocin-diabetic rats express deficits in water maze learning and hippocampal synaptic plasticity. The present study examined whether these deficits could be prevented and/or reversed with insulin treatment. In addition, the water maze learning deficit in diabetic rats was further characteriz

  3. Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.

    Science.gov (United States)

    Mahati, K; Bhagya, V; Christofer, T; Sneha, A; Shankaranarayana Rao, B S

    2016-10-01

    Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders. PMID:27555234

  4. Dysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity.

    Science.gov (United States)

    Agarwal, Amit; Zhang, Mingyue; Trembak-Duff, Irina; Unterbarnscheidt, Tilmann; Radyushkin, Konstantin; Dibaj, Payam; Martins de Souza, Daniel; Boretius, Susann; Brzózka, Magdalena M; Steffens, Heinz; Berning, Sebastian; Teng, Zenghui; Gummert, Maike N; Tantra, Martesa; Guest, Peter C; Willig, Katrin I; Frahm, Jens; Hell, Stefan W; Bahn, Sabine; Rossner, Moritz J; Nave, Klaus-Armin; Ehrenreich, Hannelore; Zhang, Weiqi; Schwab, Markus H

    2014-08-21

    Neuregulin-1 (NRG1) gene variants are associated with increased genetic risk for schizophrenia. It is unclear whether risk haplotypes cause elevated or decreased expression of NRG1 in the brains of schizophrenia patients, given that both findings have been reported from autopsy studies. To study NRG1 functions in vivo, we generated mouse mutants with reduced and elevated NRG1 levels and analyzed the impact on cortical functions. Loss of NRG1 from cortical projection neurons resulted in increased inhibitory neurotransmission, reduced synaptic plasticity, and hypoactivity. Neuronal overexpression of cysteine-rich domain (CRD)-NRG1, the major brain isoform, caused unbalanced excitatory-inhibitory neurotransmission, reduced synaptic plasticity, abnormal spine growth, altered steady-state levels of synaptic plasticity-related proteins, and impaired sensorimotor gating. We conclude that an "optimal" level of NRG1 signaling balances excitatory and inhibitory neurotransmission in the cortex. Our data provide a potential pathomechanism for impaired synaptic plasticity and suggest that human NRG1 risk haplotypes exert a gain-of-function effect. PMID:25131210

  5. ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex.

    Science.gov (United States)

    Lalo, U; Palygin, O; Verkhratsky, A; Grant, S G N; Pankratov, Y

    2016-01-01

    Recent studies highlighted the importance of astrocyte-secreted molecules, such as ATP, for the slow modulation of synaptic transmission in central neurones. Biophysical mechanisms underlying the impact of gliotransmitters on the strength of individual synapse remain, however, unclear. Here we show that purinergic P2X receptors can bring significant contribution to the signalling in the individual synaptic boutons. ATP released from astrocytes facilitates a recruitment of P2X receptors into excitatory synapses by Ca(2+)-dependent mechanism. P2X receptors, co-localized with NMDA receptors in the excitatory synapses, can be activated by ATP co-released with glutamate from pre-synaptic terminals and by glia-derived ATP. An activation of P2X receptors in turn leads to down-regulation of postsynaptic NMDA receptors via Ca(2+)-dependent de-phosphorylation and interaction with PSD-95 multi-protein complex. Genetic deletion of the PSD-95 or P2X4 receptors obliterated ATP-mediated down-regulation of NMDA receptors. Impairment of purinergic modulation of NMDA receptors in the PSD-95 mutants dramatically decreased the threshold of LTP induction and increased the net magnitude of LTP. Our findings show that synergistic action of glia- and neurone-derived ATP can pre-modulate efficacy of excitatory synapses and thereby can have an important role in the glia-neuron communications and brain meta-plasticity. PMID:27640997

  6. The transformation of synaptic to system plasticity in motor output from the sacral cord of the adult mouse.

    Science.gov (United States)

    Jiang, Mingchen C; Elbasiouny, Sherif M; Collins, William F; Heckman, C J

    2015-09-01

    Synaptic plasticity is fundamental in shaping the output of neural networks. The transformation of synaptic plasticity at the cellular level into plasticity at the system level involves multiple factors, including behavior of local networks of interneurons. Here we investigate the synaptic to system transformation for plasticity in motor output in an in vitro preparation of the adult mouse spinal cord. System plasticity was assessed from compound action potentials (APs) in spinal ventral roots, which were generated simultaneously by the axons of many motoneurons (MNs). Synaptic plasticity was assessed from intracellular recordings of MNs. A computer model of the MN pool was used to identify the middle steps in the transformation from synaptic to system behavior. Two input systems that converge on the same MN pool were studied: one sensory and one descending. The two synaptic input systems generated very different motor outputs, with sensory stimulation consistently evoking short-term depression (STD) whereas descending stimulation had bimodal plasticity: STD at low frequencies but short-term facilitation (STF) at high frequencies. Intracellular and pharmacological studies revealed contributions from monosynaptic excitation and stimulus time-locked inhibition but also considerable asynchronous excitation sustained from local network activity. The computer simulations showed that STD in the monosynaptic excitatory input was the primary driver of the system STD in the sensory input whereas network excitation underlies the bimodal plasticity in the descending system. These results provide insight on the roles of plasticity in the monosynaptic and polysynaptic inputs converging on the same MN pool to overall motor plasticity.

  7. Suppression of synaptic plasticity by fullerenol in rat hippocampus in vitro

    Directory of Open Access Journals (Sweden)

    Wang XX

    2016-09-01

    Full Text Available Xin-Xing Wang,1,2,* Ying-Ying Zha,3,* Bo Yang,1 Lin Chen,1,2 Ming Wang1,2 1CAS Key Laboratory of Brain Function and Diseases, 2Auditory Research Laboratory, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 3Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Fullerenol, a water-soluble fullerene derivative, has attracted much attention due to its bioactive properties, including the antioxidative properties and free radical scavenging ability. Due to its superior nature, fullerenol represents a promising diagnostic, therapeutic, and protective agent. Therefore, elucidation of the possible side effects of fullerenol is important in determining its potential role. In the present study, we investigated the acute effects of 5 µM fullerenol on synaptic plasticity in hippocampal brain slices of rats. Incubation with fullerenol for 20 minutes significantly decreased the peak of paired-pulse facilitation and long-term potentiation, indicating that fullerenol suppresses the short- and long-term synaptic plasticity of region I of hippocampus. We found that fullerenol depressed the activity and the expression of nitric oxide (NO synthase in hippocampus. In view of the important role of NO in synaptic plasticity, the inhibition of fullerenol on NO synthase may contribute to the suppression of synaptic plasticity. These findings may facilitate the evaluation of the side effects of fullerenol. Keywords: fullerenol, hippocampal slice, nitric oxide synthase, synaptic plasticity, oxidative stress

  8. Midbrain dopamine neurons bidirectionally regulate CA3-CA1 synaptic drive.

    Science.gov (United States)

    Rosen, Zev B; Cheung, Stephanie; Siegelbaum, Steven A

    2015-12-01

    Dopamine (DA) is required for hippocampal-dependent memory and long-term potentiation (LTP) at CA1 Schaffer collateral (SC) synapses. It is therefore surprising that exogenously applied DA has little effect on SC synapses, but suppresses CA1 perforant path (PP) inputs. To examine DA actions under more physiological conditions, we used optogenetics to release DA from ventral tegmental area inputs to hippocampus. Unlike exogenous DA application, optogenetic release of DA caused a bidirectional, activity-dependent modulation of SC synapses, with no effect on PP inputs. Low levels of DA release, simulating tonic DA neuron firing, depressed the SC response through a D4 receptor-dependent enhancement of feedforward inhibition mediated by parvalbumin-expressing interneurons. Higher levels of DA release, simulating phasic firing, increased SC responses through a D1 receptor-dependent enhancement of excitatory transmission. Thus, tonic-phasic transitions in DA neuron firing in response to motivational demands may cause a modulatory switch from inhibition to enhancement of hippocampal information flow.

  9. Associative Hebbian Synaptic Plasticity in Primate Visual Cortex

    Science.gov (United States)

    Huang, Shiyong; Rozas, Carlos; Treviño, Mario; Contreras, Jessica; Yang, Sunggu; Song, Lihua; Yoshioka, Takashi; Lee, Hey-Kyoung

    2014-01-01

    In primates, the functional connectivity of adult primary visual cortex is susceptible to be modified by sensory training during perceptual learning. It is widely held that this type of neural plasticity might involve mechanisms like long-term potentiation (LTP) and long-term depression (LTD). NMDAR-dependent forms of LTP and LTD are particularly attractive because in rodents they can be induced in a Hebbian manner by near coincidental presynaptic and postsynaptic firing, in a paradigm termed spike timing-dependent plasticity (STDP). These fundamental properties of LTP and LTD, Hebbian induction and NMDAR dependence, have not been examined in primate cortex. Here we demonstrate these properties in the primary visual cortex of the rhesus macaque (Macaca mulatta), and also show that, like in rodents, STDP is gated by neuromodulators. These findings indicate that the cellular principles governing cortical plasticity are conserved across mammalian species, further validating the use of rodents as a model system. PMID:24872561

  10. Stable Learning of Functional Maps in Self-Organizing Spiking Neural Networks with Continuous Synaptic Plasticity

    Directory of Open Access Journals (Sweden)

    Narayan eSrinivasa

    2013-02-01

    Full Text Available This study describes a spiking model that self-organizes for stable formation and maintenance of orientation and ocular dominance maps in the visual cortex (V1. This self-organization process simulates three development phases: an early experience-independent phase, a late experience-independent phase and a subsequent refinement phase during which experience acts to shape the map properties. The ocular dominance maps that emerge accommodate the two sets of monocular inputs that arise from the lateral geniculate nucleus (LGN to layer 4 of V1. The orientation selectivity maps that emerge feature well-developed iso-orientation domains and fractures. During the last two phases of development the orientation preferences at some locations appear to rotate continuously through +/- 180 along circular paths and referred to as pinwheel-like patterns but without any corresponding point discontinuities in the orientation gradient maps. The formation of these functional maps is driven by balanced excitatory and inhibitory currents that are established via synaptic plasticity based on spike timing for both excitatory and inhibitory synapses. The stability and maintenance of the formed maps with continuous synaptic plasticity is enabled by homeostasis caused by inhibitory plasticity. However, a prolonged exposure to repeated stimuli does alter the formed maps over time due to plasticity. The results from this study suggest that continuous synaptic plasticity in both excitatory neurons and interneurons could play a critical role in the formation, stability, and maintenance of functional maps in the cortex.

  11. Linking Cholinergic Interneurons, Synaptic Plasticity, and Behavior during the Extinction of a Cocaine-Context Association.

    Science.gov (United States)

    Lee, Junuk; Finkelstein, Joel; Choi, Jung Yoon; Witten, Ilana B

    2016-06-01

    Despite the fact that cholinergic interneurons are a key cell type within the nucleus accumbens, a relationship between synaptic plasticity and the in vivo activity of cholinergic interneurons remains to be established. Here, we identify a three-way link between the activity of cholinergic interneurons, synaptic plasticity, and learning in mice undergoing the extinction of a cocaine-context association. We found that activity of cholinergic interneurons regulates extinction learning for a cocaine-context association and generates a sustained reduction in glutamatergic presynaptic strength onto medium spiny neurons. Interestingly, activation of cholinergic interneurons does not support reinforcement learning or plasticity by itself, suggesting that these neurons have a modulatory rather than a reinforcing function. PMID:27210555

  12. Self-organization of a recurrent network under ongoing synaptic plasticity.

    Science.gov (United States)

    Aoki, Takaaki

    2015-02-01

    We investigated the organization of a recurrent network under ongoing synaptic plasticity using a model of neural oscillators coupled by dynamic synapses. In this model, the coupling weights changed dynamically, depending on the timing between the oscillators. We determined the phase coupling function of the oscillator model, Γ(ϕ), using conductance-based neuron models. Furthermore, we examined the effects of the Fourier zero mode of Γ(ϕ), which has a critical role in the case of spike-time-dependent plasticity-organized recurrent networks. Heterogeneous layered clusters with different frequencies emerged from homogeneous populations as the Fourier zero mode increased. Our findings may provide new insights into the self-assembly mechanisms of neural networks related to synaptic plasticity.

  13. Short-Term Synaptic Plasticity Regulation in Solution-Gated Indium-Gallium-Zinc-Oxide Electric-Double-Layer Transistors.

    Science.gov (United States)

    Wan, Chang Jin; Liu, Yang Hui; Zhu, Li Qiang; Feng, Ping; Shi, Yi; Wan, Qing

    2016-04-20

    In the biological nervous system, synaptic plasticity regulation is based on the modulation of ionic fluxes, and such regulation was regarded as the fundamental mechanism underlying memory and learning. Inspired by such biological strategies, indium-gallium-zinc-oxide (IGZO) electric-double-layer (EDL) transistors gated by aqueous solutions were proposed for synaptic behavior emulations. Short-term synaptic plasticity, such as paired-pulse facilitation, high-pass filtering, and orientation tuning, was experimentally emulated in these EDL transistors. Most importantly, we found that such short-term synaptic plasticity can be effectively regulated by alcohol (ethyl alcohol) and salt (potassium chloride) additives. Our results suggest that solution gated oxide-based EDL transistors could act as the platforms for short-term synaptic plasticity emulation. PMID:27007748

  14. Plasticity and mTOR: Towards Restoration of Impaired Synaptic Plasticity in mTOR-Related Neurogenetic Disorders

    OpenAIRE

    Gipson, Tanjala T.; Johnston, Michael V.

    2012-01-01

    Objective. To review the recent literature on the clinical features, genetic mutations, neurobiology associated with dysregulation of mTOR (mammalian target of rapamycin), and clinical trials for tuberous sclerosis complex (TSC), neurofibromatosis-1 (NF1) and fragile X syndrome (FXS), and phosphatase and tensin homolog hamartoma syndromes (PTHS), which are neurogenetic disorders associated with abnormalities in synaptic plasticity and mTOR signaling. Methods. Pubmed and Clinicaltrials.gov wer...

  15. Short-term environmental enrichment enhances synaptic plasticity in hippocampal slices from aged rats.

    Science.gov (United States)

    Stein, Liana R; O'Dell, Kazuko A; Funatsu, Michiyo; Zorumski, Charles F; Izumi, Yukitoshi

    2016-08-01

    Age-associated changes in cognition are mirrored by impairments in cellular models of memory and learning, such as long-term potentiation (LTP) and long-term depression (LTD). In young rodents, environmental enrichment (EE) can enhance memory, alter LTP and LTD, as well as reverse cognitive deficits induced by aging. Whether short-term EE can benefit cognition and synaptic plasticity in aged rodents is unclear. Here, we tested if short-term EE could overcome age-associated impairments in induction of LTP and LTD. LTP and LTD could not be induced in the CA1 region of hippocampal slices in control, aged rats using standard stimuli that are highly effective in young rats. However, exposure of aged littermates to EE for three weeks enabled successful induction of LTP and LTD. EE-facilitated LTP was dependent upon N-methyl-d-aspartate receptors (NMDARs). These alterations in synaptic plasticity occurred with elevated levels of phosphorylated cAMP response element-binding protein and vascular endothelial growth factor, but in the absence of changes in several other synaptic and cellular markers. Importantly, our study suggests that even a relatively short period of EE is sufficient to alter synaptic plasticity and molecular markers linked to cognitive function in aged animals. PMID:27208617

  16. The Roles of Protein Expression in Synaptic Plasticity and Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Tali eRosenberg

    2014-11-01

    Full Text Available The amount and availability of proteins are regulated by their synthesis, degradation, and transport. These processes can specifically, locally, and temporally regulate a protein or a population of proteins, thus affecting numerous biological processes in health and disease states. Accordingly, malfunction in the processes of protein turnover and localization underlies different neuronal diseases. However, as early as a century ago, it was recognized that there is a specific need for normal macromolecular synthesis in a specific fragment of the learning process, memory consolidation, which takes place minutes to hours following acquisition. Memory consolidation is the process by which fragile short-term memory is converted into stable long-term memory. It is accepted today that synaptic plasticity is a cellular mechanism of learning and memory processes. Interestingly, similar molecular mechanisms subserve both memory and synaptic plasticity consolidation. In this review, we survey the current view on the connection between memory consolidation processes and proteostasis, i.e., maintaining the protein contents at the neuron and the synapse. In addition, we describe the technical obstacles and possible new methods to determine neuronal proteostasis of synaptic function and better explain the process of memory and synaptic plasticity consolidation.

  17. AMPA receptor trafficking and the mechanisms underlying synaptic plasticity and cognitive aging.

    Science.gov (United States)

    Henley, Jeremy M; Wilkinson, Kevin A

    2013-03-01

    Even in healthy individuals there is an inexorable agerelated decline in cognitive function. This is due, in large part, to reduced synaptic plasticity caused by changes in the molecular composition of the postsynaptic membrane. AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate the overwhelming majority of fast excitatory transmission in the brain. Changes in AMPAR number and/or function are a core feature of synaptic plasticity and age-related cognitive decline, AMPARs are highly dynamic proteins that are subject to highly controlled trafficking, recycling, and/or degradation and replacement. This active regulation of AMPAR synthesis, targeting, synaptic dwell time, and degradation is fundamentally important for memory formation and storage. Further, aberrant AMPAR trafficking and consequent detrimental changes in synapses are strongly implicated in many brain diseases, which represent a vast social and economic burden. The purpose of this article is to provide an overview of the molecular and cellular AMPA receptor trafficking events that control synaptic responsiveness and plasticity, and highlight what is known currently known about how these processes change with age and disease. PMID:23576886

  18. Lavandula angustifolia extract improves deteriorated synaptic plasticity in an animal model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Masoud Soheili

    2015-11-01

    Full Text Available Objective(s:Neurodegenerative Alzheimer’s disease (AD is associated with profound deficits in synaptic transmission and synaptic plasticity. Long-term potentiation (LTP, an experimental form of synaptic plasticity, is intensively examined in hippocampus. In this study we evaluated the effect of aqueous extract of lavender (Lavandula angustifolia on induction of LTP in the CA1 area of hippocampus. In response to stimulation of the Schaffer collaterals the baseline or tetanized field extracellular postsynaptic potentials (fEPSPs were recorded in the CA1 area. Materials and Methods: The electrophysiological recordings were carried out in four groups of rats; two control groups including the vehicle (CON and lavender (CE treated rats and two Alzheimeric groups including the vehicle (ALZ and lavender (AE treated animals. Results: The extract inefficiently affected the baseline responses in the four testing groups. While the fEPSPs displayed a considerable LTP in the CON animals, no potentiation was evident in the tetanized responses in the ALZ rats. The herbal medicine effectively restored LTP in the AE group and further potentiated fEPSPs in the CE group. Conclusion:The positive effect of the lavender extract on the plasticity of synaptic transmission supports its previously reported behavioral effects on improvement of impaired spatial memory in the Alzheimeric animals.

  19. Spike timing-dependent plasticity as the origin of the formation of clustered synaptic efficacy engrams

    Directory of Open Access Journals (Sweden)

    Nicolangelo L Iannella

    2010-07-01

    Full Text Available Synapse location, dendritic active properties and synaptic plasticity are all known to play some role in shaping the different input streams impinging onto a neuron. It remains unclear however, how the magnitude and spatial distribution of synaptic efficacies emerge from this interplay. Here, we investigate this interplay using a biophysically detailed neuron model of a reconstructed layer 2/3 pyramidal cell and spike timing-dependent plasticity (STDP. Specifically, we focus on the issue of how the efficacy of synapses contributed by different input streams are spatially represented in dendrites after STDP learning. We construct a simple feed forward network where a detailed model neuron receives synaptic inputs independently from multiple yet equally sized groups of afferent fibres with correlated activity, mimicking the spike activity from different neuronal populations encoding, for example, different sensory modalities. Interestingly, ensuing STDP learning, we observe that for all afferent groups, STDP leads to synaptic efficacies arranged into spatially segregated clusters effectively partitioning the dendritic tree. These segregated clusters possess a characteristic global organisation in space, where they form a tessellation in which each group dominates mutually exclusive regions of the dendrite.Put simply, the dendritic imprint from different input streams left after STDP learning effectively forms what we term a dendritic efficacy mosaic. Furthermore, we show how variations of the inputs and STDP rule affect such an organization. Our model suggests that STDP may be an important mechanism for creating a clustered plasticity engram, which shapes how different input streams are spatially represented in dendrite.

  20. Correlation between synaptic plasticity, associated proteins, and rehabilitation training in a rat model of cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Dan Yang; Qian Yu

    2008-01-01

    All motions provide sensory, motoric, and reflexive input to the central nervous system, as well as playing an important role in cerebral functional plasticity and compensation. Cerebral plasticity has become the theoretical basis of neurorehabilitation. Studies of cerebrovascular disease, in particular, demonstrate that regeneration is accompanied by multiple forms of plasticity, such as functional and structural, in different phases of stroke rehabilitation. This study was designed to measure synaptic plasticity and expression of associated proteins to analyze the effect of rehabilitation training on learning and memory in a rat model of cerebral infarction. Results suggest that rehabilitation training increases expression of nerve growth factor associated protein 43, brain-derived neurotrophic factor, and neural cell adhesion molecules, and also promotes cerebral functional plasticity.

  1. Synaptic plasticity can produce and enhance direction selectivity.

    Directory of Open Access Journals (Sweden)

    Sean Carver

    2008-02-01

    Full Text Available The discrimination of the direction of movement of sensory images is critical to the control of many animal behaviors. We propose a parsimonious model of motion processing that generates direction selective responses using short-term synaptic depression and can reproduce salient features of direction selectivity found in a population of neurons in the midbrain of the weakly electric fish Eigenmannia virescens. The model achieves direction selectivity with an elementary Reichardt motion detector: information from spatially separated receptive fields converges onto a neuron via dynamically different pathways. In the model, these differences arise from convergence of information through distinct synapses that either exhibit or do not exhibit short-term synaptic depression--short-term depression produces phase-advances relative to nondepressing synapses. Short-term depression is modeled using two state-variables, a fast process with a time constant on the order of tens to hundreds of milliseconds, and a slow process with a time constant on the order of seconds to tens of seconds. These processes correspond to naturally occurring time constants observed at synapses that exhibit short-term depression. Inclusion of the fast process is sufficient for the generation of temporal disparities that are necessary for direction selectivity in the elementary Reichardt circuit. The addition of the slow process can enhance direction selectivity over time for stimuli that are sustained for periods of seconds or more. Transient (i.e., short-duration stimuli do not evoke the slow process and therefore do not elicit enhanced direction selectivity. The addition of a sustained global, synchronous oscillation in the gamma frequency range can, however, drive the slow process and enhance direction selectivity to transient stimuli. This enhancement effect does not, however, occur for all combinations of model parameters. The ratio of depressing and nondepressing synapses

  2. Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

    Institute of Scientific and Technical Information of China (English)

    Miyoung Yang; Juhwan Kim; Sung-Ho Kim; Joong-Sun Kim; Taekyun Shin; Changjong Moon

    2012-01-01

    Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, cal-cium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated dur-ing the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early (1 day post-injection) and late phases (7-14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7-14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.

  3. Possible Contributions of a Novel Form of Synaptic Plasticity in "Aplysia" to Reward, Memory, and Their Dysfunctions in Mammalian Brain

    Science.gov (United States)

    Hawkins, Robert D.

    2013-01-01

    Recent studies in "Aplysia" have identified a new variation of synaptic plasticity in which modulatory transmitters enhance spontaneous release of glutamate, which then acts on postsynaptic receptors to recruit mechanisms of intermediate- and long-term plasticity. In this review I suggest the hypothesis that similar plasticity occurs in…

  4. Excitement and synchronization of small-world neuronal networks with short-term synaptic plasticity.

    Science.gov (United States)

    Han, Fang; Wiercigroch, Marian; Fang, Jian-An; Wang, Zhijie

    2011-10-01

    Excitement and synchronization of electrically and chemically coupled Newman-Watts (NW) small-world neuronal networks with a short-term synaptic plasticity described by a modified Oja learning rule are investigated. For each type of neuronal network, the variation properties of synaptic weights are examined first. Then the effects of the learning rate, the coupling strength and the shortcut-adding probability on excitement and synchronization of the neuronal network are studied. It is shown that the synaptic learning suppresses the over-excitement, helps synchronization for the electrically coupled network but impairs synchronization for the chemically coupled one. Both the introduction of shortcuts and the increase of the coupling strength improve synchronization and they are helpful in increasing the excitement for the chemically coupled network, but have little effect on the excitement of the electrically coupled one. PMID:21956933

  5. The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Gu, Xun-Hu; Xu, Li-Jun; Liu, Zhi-Qiang; Wei, Bo; Yang, Yuan-Jian; Xu, Guo-Gang; Yin, Xiao-Ping; Wang, Wei

    2016-09-15

    Increasing evidence suggests that disruptions of synaptic functions correlate with the severity of cognitive deficit in Alzheimer's disease (AD). Our previous study demonstrated that baicalein enhances long-term potentiation (LTP) in acute rat hippocampal slices and improves hippocampus-dependent contextual fear conditioning in rats. Given that baicalein possess various biological activities, especially its effects on synaptic plasticity and cognitive function, we examined the effect of baicalein on synaptic function both in vitro and in vivo in AD model. The effect of baicalein on Aβ42 oligomer impaired LTP was investigated by electrophysiological methods. Baicalein was administered orally via drinking water to the APP/PS1 mice and sex- and age-matched wild-type mice. Treatment started at 5 months of age and mice were assessed for cognition and AD-like pathology at 7-month-old. Cognition was analyzed by Morris water maze test, fear conditioning test, and novel object recognition test. Changes in hippocampal 12/15 Lipoxygenase (12/15LO) and glycogen synthase kinase 3β (GSK3β) activity, Aβ production, tau phosphorylation, synaptic plasticity, and dendritic spine density were evaluated. Baicalein prevented Aβ-induced impairments in hippocampal LTP through activation of serine threonine Kinase (Akt) phosphorylation. Long-term oral administration of baicalein inhibited 12/15LO and GSK3β activity, reduced β-secretase enzyme (BACE1), decreased the concentration of total Aβ, and prevented phosphorylation of tau in APP/PS1 mice. Meanwhile, baicalein restored spine number, synaptic plasticity, and memory deficits. Our results strengthen the potential of the flavonoid baicalein as a novel and promising oral bioactive therapeutic agent that prevents memory deficits in AD. PMID:27233830

  6. Role of the origin of glutamatergic synaptic inputs in controlling synaptic plasticity and its modulation by alcohol in mice nucleus accumbens

    OpenAIRE

    Gilles Erwann Martin; Xincai eJi; Sucharita eSaha

    2015-01-01

    It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens, a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the nucleus accumbens receives glutamatergic inputs from distinct brain regions (e.g. the prefrontal cortex, the amygdala and the hippocampus), each region providing different informatio...

  7. Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus

    Directory of Open Access Journals (Sweden)

    John I. Broussard

    2016-03-01

    Full Text Available Dopamine release during reward-driven behaviors influences synaptic plasticity. However, dopamine innervation and release in the hippocampus and its role during aversive behaviors are controversial. Here, we show that in vivo hippocampal synaptic plasticity in the CA3-CA1 circuit underlies contextual learning during inhibitory avoidance (IA training. Immunohistochemistry and molecular techniques verified sparse dopaminergic innervation of the hippocampus from the midbrain. The long-term synaptic potentiation (LTP underlying the learning of IA was assessed with a D1-like dopamine receptor agonist or antagonist in ex vivo hippocampal slices and in vivo in freely moving mice. Inhibition of D1-like dopamine receptors impaired memory of the IA task and prevented the training-induced enhancement of both ex vivo and in vivo LTP induction. The results indicate that dopamine-receptor signaling during an aversive contextual task regulates aversive memory retention and regulates associated synaptic mechanisms in the hippocampus that likely underlie learning.

  8. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Institute of Scientific and Technical Information of China (English)

    Ling-ling Shen; Li-juan Yang; Ying Xu; Jun Dong; Ming-liang Jiang; Si-si Liu; Min-chun Cai; Zhong-qiu Hong; Li-qing Lin; Yan-yan Xing; Gui-lin Chen; Rui Pan

    2015-01-01

    Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extra-cellular microelectrode recording techniques, this study conifrmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca2+concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  9. Domestication of the dog from the wolf was promoted by enhanced excitatory synaptic plasticity: a hypothesis.

    Science.gov (United States)

    Li, Yan; Wang, Guo-Dong; Wang, Ming-Shan; Irwin, David M; Wu, Dong-Dong; Zhang, Ya-Ping

    2014-11-05

    Dogs shared a much closer relationship with humans than any other domesticated animals, probably due to their unique social cognitive capabilities, which were hypothesized to be a by-product of selection for tameness toward humans. Here, we demonstrate that genes involved in glutamate metabolism, which account partially for fear response, indeed show the greatest population differentiation by whole-genome comparison of dogs and wolves. However, the changing direction of their expression supports a role in increasing excitatory synaptic plasticity in dogs rather than reducing fear response. Because synaptic plasticity are widely believed to be cellular correlates of learning and memory, this change may alter the learning and memory abilities of ancient scavenging wolves, weaken the fear reaction toward humans, and prompt the initial interspecific contact.

  10. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Directory of Open Access Journals (Sweden)

    Ling-ling Shen

    2015-01-01

    Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  11. Presenilin-1 Mutation Impairs Cholinergic Modulation of Synaptic Plasticity and Suppresses NMDA Currents in Hippocampus slices

    OpenAIRE

    Wang, Yue; Greig, Nigel H.; Yu, Qian-Sheng; Mattson, Mark P.

    2008-01-01

    Presenilin-1 (PS1) mutations cause many cases of early-onset inherited Alzheimer's disease, in part, by increasing the production of neurotoxic forms of amyloid β-peptide (A β). However, Aβ -independent effects of mutant PS1 on neuronal Ca2+ homeostasis and sensitivity to excitatory neurotransmitters have been reported. Here we show that cholinergic modulation of hippocampal synaptic plasticity is impaired in PS1 mutant knockin (PS1KI) mice. Whereas activation of muscarinic receptors enhances...

  12. Low-frequency transcranial magnetic stimulation is beneifcial for enhancing synaptic plasticity in the aging brain

    Institute of Scientific and Technical Information of China (English)

    Zhan-chi Zhang; Feng Luan; Chun-yan Xie; Dan-dan Geng; Yan-yong Wang; Jun Ma

    2015-01-01

    In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deifcits in learning-im-paired mice. However, the mechanisms by which this treatment improves these deifcits during normal aging are still unknown. Therefore, the current study investigated the effects of tran-scranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, syn-aptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcra-nial magnetic stimulation with low intensity (110%average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippo-campus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this reg-ulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  13. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

    Directory of Open Access Journals (Sweden)

    Zhan-chi Zhang

    2015-01-01

    Full Text Available In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers, to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

  14. Spatial Regulation of Gene Expression in Neurons During Synapse Formation and Synaptic Plasticity

    OpenAIRE

    Kim, Sangmok

    2013-01-01

    mRNA localization and regulated translation allow individual neurons to locally regulate the proteome of each of their many subcellular compartments. To investigate the spatial regulation of gene expression during synaptic plasticity, we used a translational reporter system to demonstrate synapse- and stimulus-specific translation during long-term facilitation of Aplysia sensory-motor synapse. These studies revealed a role for a retrograde signal from the postsynaptic motor neuron in regulati...

  15. BACE1 Is Necessary for Experience-Dependent Homeostatic Synaptic Plasticity in Visual Cortex

    Directory of Open Access Journals (Sweden)

    Emily Petrus

    2014-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of age-related dementia, which is thought to result from overproduction and/or reduced clearance of amyloid-beta (Aβ peptides. Studies over the past few decades suggest that Aβ is produced in an activity-dependent manner and has physiological relevance to normal brain functions. Similarly, physiological functions for β- and γ-secretases, the two key enzymes that produce Aβ by sequentially processing the amyloid precursor protein (APP, have been discovered over recent years. In particular, activity-dependent production of Aβ has been suggested to play a role in homeostatic regulation of excitatory synaptic function. There is accumulating evidence that activity-dependent immediate early gene Arc is an activity “sensor,” which acts upstream of Aβ production and triggers AMPA receptor endocytosis to homeostatically downregulate the strength of excitatory synaptic transmission. We previously reported that Arc is critical for sensory experience-dependent homeostatic reduction of excitatory synaptic transmission in the superficial layers of visual cortex. Here we demonstrate that mice lacking the major neuronal β-secretase, BACE1, exhibit a similar phenotype: stronger basal excitatory synaptic transmission and failure to adapt to changes in visual experience. Our results indicate that BACE1 plays an essential role in sensory experience-dependent homeostatic synaptic plasticity in the neocortex.

  16. Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

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    Jun Hu

    Full Text Available Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+, EPSC(-, and EPSC(+/- based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs, using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+ neurons, but increased it in EPSC(- neurons. Unlike EPSC(+ and EPSC(- neurons, EPSC(+/- neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/- neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

  17. Cdk5 Modulates Long-Term Synaptic Plasticity and Motor Learning in Dorsolateral Striatum.

    Science.gov (United States)

    Hernandez, Adan; Tan, Chunfeng; Mettlach, Gabriel; Pozo, Karine; Plattner, Florian; Bibb, James A

    2016-01-01

    The striatum controls multiple cognitive aspects including motivation, reward perception, decision-making and motor planning. In particular, the dorsolateral striatum contributes to motor learning. Here we define an approach for investigating synaptic plasticity in mouse dorsolateral cortico-striatal circuitry and interrogate the relative contributions of neurotransmitter receptors and intracellular signaling components. Consistent with previous studies, we show that long-term potentiation (LTP) in cortico-striatal circuitry is facilitated by dopamine, and requires activation of D1-dopamine receptors, as well as NMDA receptors (NMDAR) and their calcium-dependent downstream effectors, including CaMKII. Moreover, we assessed the contribution of the protein kinase Cdk5, a key neuronal signaling molecule, in cortico-striatal LTP. Pharmacological Cdk5 inhibition, brain-wide Cdk5 conditional knockout, or viral-mediated dorsolateral striatal-specific loss of Cdk5 all impaired dopamine-facilitated LTP or D1-dopamine receptor-facilitated LTP. Selective loss of Cdk5 in dorsolateral striatum increased locomotor activity and attenuated motor learning. Taken together, we report an approach for studying synaptic plasticity in mouse dorsolateral striatum and critically implicate D1-dopamine receptor, NMDAR, Cdk5, and CaMKII in cortico-striatal plasticity. Furthermore, we associate striatal plasticity deficits with effects upon behaviors mediated by this circuitry. This approach should prove useful for the study of the molecular basis of plasticity in the dorsolateral striatum. PMID:27443506

  18. Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity

    KAUST Repository

    Lemtiri-Chlieh, Fouad

    2011-12-19

    Background: Dendritic spines represent the postsynaptic component of the vast majority of excitatory synapses present in the mammalian forebrain. The ability of spines to rapidly alter their shape, size, number and receptor content in response to stimulation is considered to be of paramount importance during the development of synaptic plasticity. Indeed, long-term potentiation (LTP), widely believed to be a cellular correlate of learning and memory, has been repeatedly shown to induce both spine enlargement and the formation of new dendritic spines. In our studies, we focus on Kalirin-7 (Kal7), a Rho GDP/GTP exchange factor (Rho-GEF) localized to the postsynaptic density that plays a crucial role in the development and maintenance of dendritic spines both in vitro and in vivo. Previous studies have shown that mice lacking Kal7 (Kal7 KO) have decreased dendritic spine density in the hippocampus as well as focal hippocampal-dependent learning impairments.Results: We have performed a detailed electrophysiological characterization of the role of Kal7 in hippocampal synaptic plasticity. We show that loss of Kal7 results in impaired NMDA receptor-dependent LTP and long-term depression, whereas a NMDA receptor-independent form of LTP is shown to be normal in the absence of Kal7.Conclusions: These results indicate that Kal7 is an essential and selective modulator of NMDA receptor-dependent synaptic plasticity in the hippocampus. 2011 Lemtiri-Chlieh et al; licensee BioMed Central Ltd.

  19. Endocannabinoids differentially modulate synaptic plasticity in rat hippocampal CA1 pyramidal neurons.

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    Jian-Yi Xu

    Full Text Available BACKGROUND: Hippocampal CA1 pyramidal neurons receive two excitatory glutamatergic synaptic inputs: their most distal dendritic regions in the stratum lacunosum-moleculare (SLM are innervated by the perforant path (PP, originating from layer III of the entorhinal cortex, while their more proximal regions of the apical dendrites in the stratum radiatum (SR are innervated by the Schaffer-collaterals (SC, originating from hippocampal CA3 neurons. Endocannabinoids (eCBs are naturally occurring mediators capable of modulating both GABAergic and glutamatergic synaptic transmission and plasticity via the CB1 receptor. Previous work on eCB modulation of excitatory synapses in the CA1 region largely focuses on the SC pathway. However, little information is available on whether and how eCBs modulate glutamatergic synaptic transmission and plasticity at PP synapses. METHODOLOGY/PRINCIPAL FINDINGS: By employing somatic and dendritic patch-clamp recordings, Ca(2+ uncaging, and immunostaining, we demonstrate that there are significant differences in low-frequency stimulation (LFS- or DHPG-, an agonist of group I metabotropic glutamate receptors (mGluRs, induced long-term depression (LTD of excitatory synaptic transmission between SC and PP synapses in the same pyramidal neurons. These differences are eliminated by pharmacological inhibition with selective CB1 receptor antagonists or genetic deletion of the CB1 receptor, indicating that these differences likely result from differential modulation via a CB1 receptor-dependent mechanism. We also revealed that depolarization-induced suppression of excitation (DSE, a form of short-term synaptic plasticity, and photolysis of caged Ca(2+-induced suppression of Excitatory postsynaptic currents (EPSCs were less at the PP than that at the SC. In addition, application of WIN55212 (WIN induced a more pronounced inhibition of EPSCs at the SC when compared to that at the PP. CONCLUSIONS/SIGNIFICANCE: Our results suggest

  20. Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway

    Directory of Open Access Journals (Sweden)

    Vogt Brent A

    2009-09-01

    Full Text Available Abstract Background Although the mechanisms of short- and long-term potentiation of nociceptive-evoked responses are well known in the spinal cord, including central sensitization, there has been a growing body of information on such events in the cerebral cortex. In view of the importance of anterior cingulate cortex (ACC in chronic pain conditions, this review considers neuronal plasticities in the thalamocingulate pathway that may be the earliest changes associated with such syndromes. Results A single nociceptive electrical stimulus to the sciatic nerve induced a prominent sink current in the layer II/III of the ACC in vivo, while high frequency stimulation potentiated the response of this current. Paired-pulse facilitation by electrical stimulation of midline, mediodorsal and intralaminar thalamic nuclei (MITN suggesting that the MITN projection to ACC mediates the nociceptive short-term plasticity. The short-term synaptic plasticities were evaluated for different inputs in vitro where the medial thalamic and contralateral corpus callosum afferents were compared. Stimulation of the mediodorsal afferent evoked a stronger short-term synaptic plasticity and effectively transferred the bursting thalamic activity to cingulate cortex that was not true for contralateral stimulation. This short-term enhancement of synaptic transmission was mediated by polysynaptic pathways and NMDA receptors. Layer II/III neurons of the ACC express a short-term plasticity that involves glutamate and presynaptic calcium influx and is an important mechanism of the short-term plasticity. Conclusion The potentiation of ACC neuronal activity induced by thalamic bursting suggest that short-term synaptic plasticities enable the processing of nociceptive information from the medial thalamus and this temporal response variability is particularly important in pain because temporal maintenance of the response supports cortical integration and memory formation related to

  1. Synaptic plasticity in medial vestibular nucleus neurons: comparison with computational requirements of VOR adaptation.

    Directory of Open Access Journals (Sweden)

    John R W Menzies

    Full Text Available BACKGROUND: Vestibulo-ocular reflex (VOR gain adaptation, a longstanding experimental model of cerebellar learning, utilizes sites of plasticity in both cerebellar cortex and brainstem. However, the mechanisms by which the activity of cortical Purkinje cells may guide synaptic plasticity in brainstem vestibular neurons are unclear. Theoretical analyses indicate that vestibular plasticity should depend upon the correlation between Purkinje cell and vestibular afferent inputs, so that, in gain-down learning for example, increased cortical activity should induce long-term depression (LTD at vestibular synapses. METHODOLOGY/PRINCIPAL FINDINGS: Here we expressed this correlational learning rule in its simplest form, as an anti-Hebbian, heterosynaptic spike-timing dependent plasticity interaction between excitatory (vestibular and inhibitory (floccular inputs converging on medial vestibular nucleus (MVN neurons (input-spike-timing dependent plasticity, iSTDP. To test this rule, we stimulated vestibular afferents to evoke EPSCs in rat MVN neurons in vitro. Control EPSC recordings were followed by an induction protocol where membrane hyperpolarizing pulses, mimicking IPSPs evoked by flocculus inputs, were paired with single vestibular nerve stimuli. A robust LTD developed at vestibular synapses when the afferent EPSPs coincided with membrane hyperpolarization, while EPSPs occurring before or after the simulated IPSPs induced no lasting change. Furthermore, the iSTDP rule also successfully predicted the effects of a complex protocol using EPSP trains designed to mimic classical conditioning. CONCLUSIONS: These results, in strong support of theoretical predictions, suggest that the cerebellum alters the strength of vestibular synapses on MVN neurons through hetero-synaptic, anti-Hebbian iSTDP. Since the iSTDP rule does not depend on post-synaptic firing, it suggests a possible mechanism for VOR adaptation without compromising gaze-holding and VOR

  2. A role for calcium-permeable AMPA receptors in synaptic plasticity and learning.

    Directory of Open Access Journals (Sweden)

    Brian J Wiltgen

    Full Text Available A central concept in the field of learning and memory is that NMDARs are essential for synaptic plasticity and memory formation. Surprisingly then, multiple studies have found that behavioral experience can reduce or eliminate the contribution of these receptors to learning. The cellular mechanisms that mediate learning in the absence of NMDAR activation are currently unknown. To address this issue, we examined the contribution of Ca(2+-permeable AMPARs to learning and plasticity in the hippocampus. Mutant mice were engineered with a conditional genetic deletion of GluR2 in the CA1 region of the hippocampus (GluR2-cKO mice. Electrophysiology experiments in these animals revealed a novel form of long-term potentiation (LTP that was independent of NMDARs and mediated by GluR2-lacking Ca(2+-permeable AMPARs. Behavioral analyses found that GluR2-cKO mice were impaired on multiple hippocampus-dependent learning tasks that required NMDAR activation. This suggests that AMPAR-mediated LTP interferes with NMDAR-dependent plasticity. In contrast, NMDAR-independent learning was normal in knockout mice and required the activation of Ca(2+-permeable AMPARs. These results suggest that GluR2-lacking AMPARs play a functional and previously unidentified role in learning; they appear to mediate changes in synaptic strength that occur after plasticity has been established by NMDARs.

  3. Role of the origin of glutamatergic synaptic inputs in controlling synaptic plasticity and its modulation by alcohol in mice nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Gilles Erwann Martin

    2015-07-01

    Full Text Available It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens, a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the nucleus accumbens receives glutamatergic inputs from distinct brain regions (e.g. the prefrontal cortex, the amygdala and the hippocampus, each region providing different information (e.g. spatial, emotional and cognitive. Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD and long-term potentiation (tLTP and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute EtOH has little effects on higher order information coming from the prefrontal cortex (PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

  4. Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease

    Directory of Open Access Journals (Sweden)

    G. D’Arcangelo

    2016-01-01

    Full Text Available Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1−/− mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1−/− mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1−/− mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia.

  5. Alzheimer’s disease Aβ assemblies mediating rapid disruption of synaptic plasticity and memory

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    Klyubin Igor

    2012-07-01

    Full Text Available Abstract Alzheimer’s disease (AD is characterized by episodic memory impairment that often precedes clinical diagnosis by many years. Probing the mechanisms of such impairment may provide much needed means of diagnosis and therapeutic intervention at an early, pre-dementia, stage. Prior to the onset of significant neurodegeneration, the structural and functional integrity of synapses in mnemonic circuitry is severely compromised in the presence of amyloidosis. This review examines recent evidence evaluating the role of amyloid-ß protein (Aβ in causing rapid disruption of synaptic plasticity and memory impairment. We evaluate the relative importance of different sizes and conformations of Aβ, including monomer, oligomer, protofibril and fibril. We pay particular attention to recent controversies over the relevance to the pathophysiology of AD of different water soluble Aβ aggregates and the importance of cellular prion protein in mediating their effects. Current data are consistent with the view that both low-n oligomers and larger soluble assemblies present in AD brain, some of them via a direct interaction with cellular prion protein, cause synaptic memory failure. At the two extremes of aggregation, monomers and fibrils appear to act in vivo both as sources and sinks of certain metastable conformations of soluble aggregates that powerfully disrupt synaptic plasticity. The same principle appears to apply to other synaptotoxic amyloidogenic proteins including tau, α-synuclein and prion protein.

  6. On Analysis of Quantifying Learning Creativity Phenomenon Considering Brain Synaptic Plasticity

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    Hassan Mustafa

    2009-06-01

    Full Text Available Generally, Analysis of learning creativity phenomenon is an interesting and challenging issue associated with educational practice. Moreover, that phenomenon is tightly related to main human brain functions (Learning and Memory. So, creative individuals are characterized by their distinct capabilities in performing both brain functions. Additionally, educationalists as well as psychologists, for a long time ago and until recently, have been interesting in searching for quantitative investigation of that challenging issue. In the field of education, practical evaluation of learners' performance, -during tutoring session(s - may result in observation of creativity phenomenon. Herein, this work introduces an interdisciplinary novel approach concerned with analysis of quantifying learning creativity phenomenon. That is fulfilled by adopting Artificial Neural Networks modeling for realistic simulation of synaptic connectivity dynamics (equivalently, synaptic plasticity. By some details, presented work considered two main design parameters of Artificial Neural Networks. Namely they are, gain factor (of neuronal sigmoid activation function, and learning rate value. Both parameters Synaptic Plasticity inside the brain. Obviously, individuals characterized by various values of gain factor value as well as learning rate parameter are well relevant to quantify there learning creativity. Conclusively, obtained results motivate future research for systematical investigational study in depth considering the effect of congenital and/or hereditary factors on learning creativity phenomenon.

  7. UBE3A Regulates Synaptic Plasticity and Learning and Memory by Controlling SK2 Channel Endocytosis

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    Jiandong Sun

    2015-07-01

    Full Text Available Gated solely by activity-induced changes in intracellular calcium, small-conductance potassium channels (SKs are critical for a variety of functions in the CNS, from learning and memory to rhythmic activity and sleep. While there is a wealth of information on SK2 gating, kinetics, and Ca2+ sensitivity, little is known regarding the regulation of SK2 subcellular localization. We report here that synaptic SK2 levels are regulated by the E3 ubiquitin ligase UBE3A, whose deficiency results in Angelman syndrome and overexpression in increased risk of autistic spectrum disorder. UBE3A directly ubiquitinates SK2 in the C-terminal domain, which facilitates endocytosis. In UBE3A-deficient mice, increased postsynaptic SK2 levels result in decreased NMDA receptor activation, thereby impairing hippocampal long-term synaptic plasticity. Impairments in both synaptic plasticity and fear conditioning memory in UBE3A-deficient mice are significantly ameliorated by blocking SK2. These results elucidate a mechanism by which UBE3A directly influences cognitive function.

  8. Magnesium protects cognitive functions and synaptic plasticity in streptozotocin-induced sporadic Alzheimer's model.

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    Zhi-Peng Xu

    Full Text Available Alzheimer's disease (AD is characterized by profound synapse loss and impairments of learning and memory. Magnesium affects many biochemical mechanisms that are vital for neuronal properties and synaptic plasticity. Recent studies have demonstrated that the serum and brain magnesium levels are decreased in AD patients; however, the exact role of magnesium in AD pathogenesis remains unclear. Here, we found that the intraperitoneal administration of magnesium sulfate increased the brain magnesium levels and protected learning and memory capacities in streptozotocin-induced sporadic AD model rats. We also found that magnesium sulfate reversed impairments in long-term potentiation (LTP, dendritic abnormalities, and the impaired recruitment of synaptic proteins. Magnesium sulfate treatment also decreased tau hyperphosphorylation by increasing the inhibitory phosphorylation of GSK-3β at serine 9, thereby increasing the activity of Akt at Ser473 and PI3K at Tyr458/199, and improving insulin sensitivity. We conclude that magnesium treatment protects cognitive function and synaptic plasticity by inhibiting GSK-3β in sporadic AD model rats, which suggests a potential role for magnesium in AD therapy.

  9. Mind Bomb-2 Regulates Hippocampus-dependent Memory Formation and Synaptic Plasticity.

    Science.gov (United States)

    Kim, Somi; Kim, TaeHyun; Lee, Hye-Ryeon; Kong, Young-Yun; Kaang, Bong-Kiun

    2015-11-01

    Notch signaling is a key regulator of neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-2 (Mib2) is an essential positive regulator of the Notch pathway, which acts in the Notch signal-sending cells. Therefore, genetic deletion of Mib2 in the mouse brain might help understand Notch signaling-mediated cell-cell interactions between neurons and their physiological function. Here we show that deletion of Mib2 in the mouse brain results in impaired hippocampal spatial memory and contextual fear memory. Accordingly, we found impaired hippocampal synaptic plasticity in Mib2 knock-out (KO) mice; however, basal synaptic transmission did not change at the Schaffer collateral-CA1 synapses. Using western blot analysis, we found that the level of cleaved Notch1 was lower in Mib2 KO mice than in wild type (WT) littermates after mild foot shock. Taken together, these data suggest that Mib2 plays a critical role in synaptic plasticity and spatial memory through the Notch signaling pathway.

  10. Calcineurin inhibition rescues early synaptic plasticity deficits in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Cavallucci, Virve; Berretta, Nicola; Nobili, Annalisa; Nisticò, Robert; Mercuri, Nicola B; D'Amelio, Marcello

    2013-09-01

    Functional and ultrastructural investigations support the concept that altered brain connectivity, exhausted neural plasticity, and synaptic loss are the strongest correlates of cognitive decline in age-related neurodegenerative dementia of Alzheimer's type. We have previously demonstrated that in transgenic mice, expressing amyloid-β precursor protein-Swedish mutation active caspase-3 accumulates in hippocampal postsynaptic compartments leading to altered postsynaptic density (PSD) composition, increased long-term depression (LTD), and dendritic spine loss. Furthermore, we found strong evidence that dendritic spine alteration is mediated by calcineurin activation, a calcium-dependent phosphatase involved in synapse signaling. In the present work, we analyzed the molecular mechanism linking alteration of synaptic plasticity to the increase of calcineurin activity. We found that acute treatment of young and plaque-free transgenic mice with the calcineurin inhibitor FK506 leads to a complete rescue of LTD and PSD composition. Our findings are in agreement with other results reporting that calcineurin inhibition improves memory function and restores dendritic spine density, confirming that calcineurin inhibition may be explored as a neuroprotective treatment to stop or slowdown synaptic alterations in Alzheimer's disease.

  11. A light-stimulated synaptic transistor with synaptic plasticity and memory functions based on InGaZnOx-Al2O3 thin film structure

    Science.gov (United States)

    Li, H. K.; Chen, T. P.; Liu, P.; Hu, S. G.; Liu, Y.; Zhang, Q.; Lee, P. S.

    2016-06-01

    In this work, a synaptic transistor based on the indium gallium zinc oxide (IGZO)-aluminum oxide (Al2O3) thin film structure, which uses ultraviolet (UV) light pulses as the pre-synaptic stimulus, has been demonstrated. The synaptic transistor exhibits the behavior of synaptic plasticity like the paired-pulse facilitation. In addition, it also shows the brain's memory behaviors including the transition from short-term memory to long-term memory and the Ebbinghaus forgetting curve. The synapse-like behavior and memory behaviors of the transistor are due to the trapping and detrapping processes of the holes, which are generated by the UV pulses, at the IGZO/Al2O3 interface and/or in the Al2O3 layer.

  12. Exposure to low-dose rotenone precipitates synaptic plasticity alterations in PINK1 heterozygous knockout mice.

    Science.gov (United States)

    Martella, G; Madeo, G; Maltese, M; Vanni, V; Puglisi, F; Ferraro, E; Schirinzi, T; Valente, E M; Bonanni, L; Shen, J; Mandolesi, G; Mercuri, N B; Bonsi, P; Pisani, A

    2016-07-01

    Heterozygous mutations in the PINK1 gene are considered a susceptibility factor to develop early-onset Parkinson's disease (PD), as supported by dopamine hypometabolism in asymptomatic mutation carriers and subtle alterations of dopamine-dependent striatal synaptic plasticity in heterozygous PINK1 knockout (PINK1(+/-)) mice. The aim of the present study was to investigate whether exposure to low-dose rotenone of heterozygous PINK1(+/-) mice, compared to their wild-type PINK1(+/+) littermates, could impact on dopamine-dependent striatal synaptic plasticity, in the absence of apparent structural alterations. Mice were exposed to a range of concentrations of rotenone (0.01-1mg/kg). Chronic treatment with concentrations of rotenone up to 0.8mg/kg did not cause manifest neuronal loss or changes in ATP levels both in the striatum or substantia nigra of PINK1(+/-) and PINK1(+/+) mice. Moreover, rotenone (up to 0.8mg/kg) treatment did not induce mislocalization of the mitochondrial membrane protein Tom20 and release of cytochrome c in PINK1(+/-) striata. Accordingly, basic electrophysiological properties of nigral dopaminergic and striatal medium spiny neurons (MSNs) were normal. Despite the lack of gross alterations in neuronal viability in chronically-treated PINK1(+/-), a complete loss of both long-term depression (LTD) and long-term potentiation (LTP) was recorded in MSNs from PINK1(+/-) mice treated with a low rotenone (0.1mg/kg) concentration. Even lower concentrations (0.01mg/kg) blocked LTP induction in heterozygous PINK1(+/-) MSNs compared to PINK1(+/+) mice. Of interest, chronic pretreatment with the antioxidants alpha-tocopherol and Trolox, a water-soluble analog of vitamin E and powerful antioxidant, rescued synaptic plasticity impairment, confirming that, at the doses we utilized, rotenone did not induce irreversible alterations. In this model, chronic exposure to low-doses of rotenone was not sufficient to alter mitochondrial integrity and ATP production, but

  13. Plasticity and mTOR: Towards Restoration of Impaired Synaptic Plasticity in mTOR-Related Neurogenetic Disorders

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    Tanjala T. Gipson

    2012-01-01

    Full Text Available Objective. To review the recent literature on the clinical features, genetic mutations, neurobiology associated with dysregulation of mTOR (mammalian target of rapamycin, and clinical trials for tuberous sclerosis complex (TSC, neurofibromatosis-1 (NF1 and fragile X syndrome (FXS, and phosphatase and tensin homolog hamartoma syndromes (PTHS, which are neurogenetic disorders associated with abnormalities in synaptic plasticity and mTOR signaling. Methods. Pubmed and Clinicaltrials.gov were searched using specific search strategies. Results/Conclusions. Although traditionally thought of as irreversible disorders, significant scientific progress has been made in both humans and preclinical models to understand how pathologic features of these neurogenetic disorders can be reduced or reversed. This paper revealed significant similarities among the conditions. Not only do they share features of impaired synaptic plasticity and dysregulation of mTOR, but they also share clinical features—autism, intellectual disability, cutaneous lesions, and tumors. Although scientific advances towards discovery of effective treatment in some disorders have outpaced others, progress in understanding the signaling pathways that connect the entire group indicates that the lesser known disorders will become treatable as well.

  14. Role of immediate-early genes in synaptic plasticity and neuronal ensembles underlying the memory trace

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    Keiichiro eMinatohara

    2016-01-01

    Full Text Available In the brain, neuronal gene expression is dynamically changed in response to neuronal activity. In particular, the expression of immediate-early genes (IEGs such as egr-1, c-fos, and Arc is rapidly and selectively upregulated in subsets of neurons in specific brain regions associated with learning and memory formation. IEG expression has therefore been widely used as a molecular marker for neuronal populations that undergo plastic changes underlying formation of long-term memory. In recent years, optogenetic and pharmacogenetic studies of neurons expressing c-fos or Arc have revealed that, during learning, IEG-positive neurons encode and store information that is required for memory recall, suggesting that they may be involved in formation of the memory trace. However, despite accumulating evidence for the role of IEGs in synaptic plasticity, the molecular and cellular mechanisms associated with this process remain unclear. In this review, we first summarize recent literature concerning the role of IEG-expressing neuronal ensembles in organizing the memory trace. We then focus on the physiological significance of IEGs, especially Arc, in synaptic plasticity, and describe our hypotheses about the importance of Arc expression in various types of input-specific circuit reorganization. Finally, we offer perspectives on Arc function that would unveil the role of IEG-expressing neurons in the formation of memory traces in the hippocampus and other brain areas.

  15. PRG-1 Regulates Synaptic Plasticity via Intracellular PP2A/β1-Integrin Signaling.

    Science.gov (United States)

    Liu, Xingfeng; Huai, Jisen; Endle, Heiko; Schlüter, Leslie; Fan, Wei; Li, Yunbo; Richers, Sebastian; Yurugi, Hajime; Rajalingam, Krishnaraj; Ji, Haichao; Cheng, Hong; Rister, Benjamin; Horta, Guilherme; Baumgart, Jan; Berger, Hendrik; Laube, Gregor; Schmitt, Ulrich; Schmeisser, Michael J; Boeckers, Tobias M; Tenzer, Stefan; Vlachos, Andreas; Deller, Thomas; Nitsch, Robert; Vogt, Johannes

    2016-08-01

    Alterations in dendritic spine numbers are linked to deficits in learning and memory. While we previously revealed that postsynaptic plasticity-related gene 1 (PRG-1) controls lysophosphatidic acid (LPA) signaling at glutamatergic synapses via presynaptic LPA receptors, we now show that PRG-1 also affects spine density and synaptic plasticity in a cell-autonomous fashion via protein phosphatase 2A (PP2A)/β1-integrin activation. PRG-1 deficiency reduces spine numbers and β1-integrin activation, alters long-term potentiation (LTP), and impairs spatial memory. The intracellular PRG-1 C terminus interacts in an LPA-dependent fashion with PP2A, thus modulating its phosphatase activity at the postsynaptic density. This results in recruitment of adhesome components src, paxillin, and talin to lipid rafts and ultimately in activation of β1-integrins. Consistent with these findings, activation of PP2A with FTY720 rescues defects in spine density and LTP of PRG-1-deficient animals. These results disclose a mechanism by which bioactive lipid signaling via PRG-1 could affect synaptic plasticity and memory formation. PMID:27453502

  16. Altered hippocampal long-term synaptic plasticity in mice deficient in the PGE2 EP2 receptor

    Science.gov (United States)

    Yang, Hongwei; Zhang, Jian; Breyer, Richard M.; Chen, Chu

    2008-01-01

    Our laboratory demonstrated previously that PGE2-induced modulation of hippocampal synaptic transmission is via a presynaptic PGE2 EP2 receptor. However, little is known about whether the EP2 receptor is involved in hippocampal long-term synaptic plasticity and cognitive function. Here we show that long-term potentiation (LTP) at the hippocampal perforant path synapses was impaired in mice deficient in the EP2 (KO), while membrane excitability and passive properties in granule neurons were normal. Importantly, escape latency in the water maze in EP2 KO was longer than that in age-matched EP2 wild-type littermates (WT). We also observed that LTP was potentiated in EP2 WT animals that received lipopolysaccharide (LPS, i.p.), but not in EP2 KO. Bath application of PGE2 or butaprost, an EP2 receptor agonist, increased synaptic transmission and decreased paired-pulses ratio (PPR) in EP2 WT mice, but failed to induce the changes in EP2 KO mice. Meanwhile, synaptic transmission was elevated by application of forskolin, an adenylyl cyclase activator, both in EP2 KO and WT animals. In addition, the PGE2-enhanced synaptic transmission was significantly attenuated by application of PKA, IP3 or MAPK inhibitors in EP2 WT animals. Our results show that hippocampal long-term synaptic plasticity is impaired in mice deficient in the EP2, suggesting that PGE2-EP2 signaling is important for hippocampal long-term synaptic plasticity and cognitive function. PMID:19012750

  17. Unsupervised Discrimination of Patterns in Spiking Neural Networks with Excitatory and Inhibitory Synaptic Plasticity

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    Narayan eSrinivasa

    2014-12-01

    Full Text Available A spiking neural network model is described for learning to discriminate among spatial patterns in an unsupervised manner. The network anatomy consists of source neurons that are activated by external inputs, a reservoir that resembles a generic cortical layer with an excitatory-inhibitory (EI network and a sink layer of neurons for readout. Synaptic plasticity in the form of STDP is imposed on all the excitatory and inhibitory synapses at all times. While long-term excitatory STDP enables sparse and efficient learning of the salient features in inputs, inhibitory STDP enables this learning to be stable by establishing a balance between excitatory and inhibitory currents at each neuron in the network. The synaptic weights between source and reservoir neurons form a basis set for the input patterns. The neural trajectories generated in the reservoir due to input stimulation and lateral connections between reservoir neurons can be readout by the sink layer neurons. This activity is used for adaptation of synapses between reservoir and sink layer neurons. A new measure called the discriminability index (DI is introduced to compute if the network can discriminate between old patterns already presented in an initial training session. The DI is also used to compute if the network adapts to new patterns without losing its ability to discriminate among old patterns. The final outcome is that the network is able to correctly discriminate between all patterns – both old and new. This result holds as long as inhibitory synapses employ STDP to continuously enable current balance in the network. The results suggest a possible direction for future investigation into how spiking neural networks could address the stability-plasticity question despite having continuous synaptic plasticity.

  18. MAGI-1 modulates AMPA receptor synaptic localization and behavioral plasticity in response to prior experience.

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    Lesley Emtage

    Full Text Available It is well established that the efficacy of synaptic connections can be rapidly modified by neural activity, yet how the environment and prior experience modulate such synaptic and behavioral plasticity is only beginning to be understood. Here we show in C. elegans that the broadly conserved scaffolding molecule MAGI-1 is required for the plasticity observed in a glutamatergic circuit. This mechanosensory circuit mediates reversals in locomotion in response to touch stimulation, and the AMPA-type receptor (AMPAR subunits GLR-1 and GLR-2, which are required for reversal behavior, are localized to ventral cord synapses in this circuit. We find that animals modulate GLR-1 and GLR-2 localization in response to prior mechanosensory stimulation; a specific isoform of MAGI-1 (MAGI-1L is critical for this modulation. We show that MAGI-1L interacts with AMPARs through the intracellular domain of the GLR-2 subunit, which is required for the modulation of AMPAR synaptic localization by mechanical stimulation. In addition, mutations that prevent the ubiquitination of GLR-1 prevent the decrease in AMPAR localization observed in previously stimulated magi-1 mutants. Finally, we find that previously-stimulated animals later habituate to subsequent mechanostimulation more rapidly compared to animals initially reared without mechanical stimulation; MAGI-1L, GLR-1, and GLR-2 are required for this change in habituation kinetics. Our findings demonstrate that prior experience can cause long-term alterations in both behavioral plasticity and AMPAR localization at synapses in an intact animal, and indicate a new, direct role for MAGI/S-SCAM proteins in modulating AMPAR localization and function in the wake of variable sensory experience.

  19. Nucleolar integrity is required for the maintenance of long-term synaptic plasticity.

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    Kim D Allen

    Full Text Available Long-term memory (LTM formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose polymerase-1 (PARP-1, are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosylation (PAR dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP ribose molecules (pADPr after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA and extracellular signal-regulated kinase (ERK--two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I, responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components--hence, new ribosomes and nucleoli integrity--are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation.

  20. Chronic alcohol exposure alters behavioral and synaptic plasticity of the rodent prefrontal cortex.

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    Sven Kroener

    Full Text Available In the present study, we used a mouse model of chronic intermittent ethanol (CIE exposure to examine how CIE alters the plasticity of the medial prefrontal cortex (mPFC. In acute slices obtained either immediately or 1-week after the last episode of alcohol exposure, voltage-clamp recording of excitatory post-synaptic currents (EPSCs in mPFC layer V pyramidal neurons revealed that CIE exposure resulted in an increase in the NMDA/AMPA current ratio. This increase appeared to result from a selective increase in the NMDA component of the EPSC. Consistent with this, Western blot analysis of the postsynaptic density fraction showed that while there was no change in expression of the AMPA GluR1 subunit, NMDA NR1 and NRB subunits were significantly increased in CIE exposed mice when examined immediately after the last episode of alcohol exposure. Unexpectedly, this increase in NR1 and NR2B was no longer observed after 1-week of withdrawal in spite of a persistent increase in synaptic NMDA currents. Analysis of spines on the basal dendrites of layer V neurons revealed that while the total density of spines was not altered, there was a selective increase in the density of mushroom-type spines following CIE exposure. Examination of NMDA-receptor mediated spike-timing-dependent plasticity (STDP showed that CIE exposure was associated with altered expression of long-term potentiation (LTP. Lastly, behavioral studies using an attentional set-shifting task that depends upon the mPFC for optimal performance revealed deficits in cognitive flexibility in CIE exposed mice when tested up to 1-week after the last episode of alcohol exposure. Taken together, these observations are consistent with those in human alcoholics showing protracted deficits in executive function, and suggest these deficits may be associated with alterations in synaptic plasticity in the mPFC.

  1. Kidins220/ARMS is a novel modulator of short-term synaptic plasticity in hippocampal GABAergic neurons.

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    Joachim Scholz-Starke

    Full Text Available Kidins220 (Kinase D interacting substrate of 220 kDa/ARMS (Ankyrin Repeat-rich Membrane Spanning is a scaffold protein highly expressed in the nervous system. Previous work on neurons with altered Kidins220/ARMS expression suggested that this protein plays multiple roles in synaptic function. In this study, we analyzed the effects of Kidins220/ARMS ablation on basal synaptic transmission and on a variety of short-term plasticity paradigms in both excitatory and inhibitory synapses using a recently described Kidins220 full knockout mouse. Hippocampal neuronal cultures prepared from embryonic Kidins220(-/- (KO and wild type (WT littermates were used for whole-cell patch-clamp recordings of spontaneous and evoked synaptic activity. Whereas glutamatergic AMPA receptor-mediated responses were not significantly affected in KO neurons, specific differences were detected in evoked GABAergic transmission. The recovery from synaptic depression of inhibitory post-synaptic currents in WT cells showed biphasic kinetics, both in response to paired-pulse and long-lasting train stimulation, while in KO cells the respective slow components were strongly reduced. We demonstrate that the slow recovery from synaptic depression in WT cells is caused by a transient reduction of the vesicle release probability, which is absent in KO neurons. These results suggest that Kidins220/ARMS is not essential for basal synaptic transmission and various forms of short-term plasticity, but instead plays a novel role in the mechanisms regulating the recovery of synaptic strength in GABAergic synapses.

  2. The temporoammonic input to the hippocampal CA1 region displays distinctly different synaptic plasticity compared to the Schaffer collateral input in vivo: significance for synaptic information processing

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    Ayla eAksoy Aksel

    2013-08-01

    Full Text Available In terms of its sub-regional differentiation, the hippocampal CA1 region receives cortical information directly via the perforant (temporoammonic path (pp-CA1 synapse and indirectly via the tri-synaptic pathway where the last relay station is the Schaffer collateral-CA1 synapse (Sc-CA1 synapse. Research to date on pp-CA1 synapses has been conducted predominantly in vitro and never in awake animals, but these studies hint that information processing at this synapse might be distinct to processing at the Sc-CA1 synapse. Here, we characterized synaptic properties and synaptic plasticity at the pp-CA1 synapse of freely behaving adult rats. We established that field excitatory postsynaptic potentials at the pp-CA1 have longer onset latencies and a shorter time-to-peak compared to the Sc-CA1 synapse. LTP (> 24h was successfully evoked by tetanic afferent stimulation of pp-CA1 synapses. Low frequency stimulation evoked synaptic depression at Sc-CA1 synapses, but did not elicit LTD at pp-CA1 synapses unless the Schaffer collateral afferents to the CA1 region had been severed. Paired-pulse responses also showed significant differences. Our data suggest that synaptic plasticity at the pp-CA1 synapse is distinct from the Sc-CA1 synapse and that this may reflect its specific role in hippocampal information processing.

  3. Wherefore Art Thou, Homeo(stasis? Functional Diversity in Homeostatic Synaptic Plasticity

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    Bridget N. Queenan

    2012-01-01

    Full Text Available Homeostatic plasticity has emerged as a fundamental regulatory principle that strives to maintain neuronal activity within optimal ranges by altering diverse aspects of neuronal function. Adaptation to network activity is often viewed as an essential negative feedback restraint that prevents runaway excitation or inhibition. However, the precise importance of these homeostatic functions is often theoretical rather than empirically derived. Moreover, a remarkable multiplicity of homeostatic adaptations has been observed. To clarify these issues, it may prove useful to ask: why do homeostatic mechanisms exist, what advantages do these adaptive responses confer on a given cell population, and why are there so many seemingly divergent effects? Here, we approach these questions by applying the principles of control theory to homeostatic synaptic plasticity of mammalian neurons and suggest that the varied responses observed may represent distinct functional classes of control mechanisms directed toward disparate physiological goals.

  4. Regulation of Astroglia on Synaptic Plasticity in the CA1 Region of Rat Hippocampus

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The regulation of astroglia on synaptic plasticity in the CA1 region of rat hippocampus was examined. Rats were divided into three groups: the newly born (<24 h), the juvenile (28-30days) and the adult groups (90-100 days), with each group having 20 animals. The CA1 region of rat hippocampus was immunohistochemically and electron-microscopically examined, respectively,for the growth of astroglia and the ultrastructure of synapses. The high performance liquid chromatography was employed to determine the cholesterol content of rat hippocampus. In the newly-born rats, a large number of neurons were noted in the hippocampal CA1 region of the newly-born rats,and few astroglia and no synaptic structure were observed. In the juvenile group, a few astroglias and some immature synapses were found, which were less than those in adult rats (P<0.01). The cholesterol content was 2.92±0.03 mg/g, 11.20± 3.41 mg/g and 12.91 ± 1.25 mg/g for newly born, the juvenile and the adult groups, respectively, with the differences among them being statistically significant (P<0.01). Our study suggests that the astrocytes may play an important role in the synaptic formation and functional maturity of hippocampal neurons, which may be related to the secretion of cholesterol from astrocytes.

  5. Ribbon Synaptic Plasticity in Gravity Sensors of Rats Flown on Neurolab

    Science.gov (United States)

    Ross, Muriel D.; Varelas, Joseph

    2003-01-01

    Previous spaceflight experiments (Space Life Sciences-1 and -2 (SLS-1 and SLS-2)) first demonstrated the extraordinary ability of gravity sensor hair cells to change the number, kind, and distribution of connections (synapses) they make to other cells while in weightlessness. The number of synapses in hair cells in one part of the inner ear (the utricle) was markedly elevated on flight day 13 (FD13) of SLS-2. Unanswered questions, however, were whether these increases in synapses occur rapidly and whether they remain stable in weightlessness. The answers have implications for long-duration human space travel. If gravity sensors can adapt quickly, crews may be able to move easily between different gravity levels, since the sensors will adapt rapidly to weightlessness on the spacecraft and then back to Earth's gravity when the mission ends. This ability to adapt is also important for recovery from balance disorders. To further our understanding of this adaptive potential (a property called neuronal synaptic plasticity), the present Neurolab research was undertaken. Our experiment examined whether: (a) increases in synapses would remain stable throughout the flight, (b) changes in the number of synapses were uniform across different portions of the gravity sensors (the utricle and saccule), and (c) synaptic changes were similar for the different types of hair cells (Type I and Type II). Utricular and saccular maculae (the gravity-sensing portions of the inner ear) were collected in flight from rats on FD2 and FD14. Samples were also collected from control rats on the ground. Tissues were prepared for ultrastructural study. Hair cells and their ribbon synapses were examined in a transmission electron microscope. Synapses were counted in all hair cells in 50 consecutive sections that crossed the striolar zone. Results indicate that utricular hair cell synapses initially increased significantly in number in both types of hair cells by FD2. Counts declined by FD14, but

  6. Altered hippocampal long-term synaptic plasticity in mice deficient in the PGE2 EP2 receptor

    OpenAIRE

    Yang, Hongwei; Zhang, Jian; Breyer, Richard M.; Chen, Chu

    2008-01-01

    Our laboratory demonstrated previously that PGE2-induced modulation of hippocampal synaptic transmission is via a presynaptic PGE2 EP2 receptor. However, little is known about whether the EP2 receptor is involved in hippocampal long-term synaptic plasticity and cognitive function. Here we show that long-term potentiation (LTP) at the hippocampal perforant path synapses was impaired in mice deficient in the EP2 (KO), while membrane excitability and passive properties in granule neurons were no...

  7. Kidins220/ARMS Is a Novel Modulator of Short-Term Synaptic Plasticity in Hippocampal GABAergic Neurons

    OpenAIRE

    Joachim Scholz-Starke; Fabrizia Cesca; Giampietro Schiavo; Fabio Benfenati; Pietro Baldelli

    2012-01-01

    Kidins220 (Kinase D interacting substrate of 220 kDa)/ARMS (Ankyrin Repeat-rich Membrane Spanning) is a scaffold protein highly expressed in the nervous system. Previous work on neurons with altered Kidins220/ARMS expression suggested that this protein plays multiple roles in synaptic function. In this study, we analyzed the effects of Kidins220/ARMS ablation on basal synaptic transmission and on a variety of short-term plasticity paradigms in both excitatory and inhibitory synapses using a r...

  8. Priming stimulation modifies synaptic plasticity in the perforant path of hippocampal slice in rat

    Institute of Scientific and Technical Information of China (English)

    Lian ZHANG; Hong-Mei XIAO; Yan-Xia ZHOU; Xiao-Ping LUO

    2006-01-01

    Objective The potential of all central nervous system synapses to exhibit long term potentiation (LTP) or long term depression (LTD) is subject to modulation by prior synaptic activity, a higher-order form of plasticity that has been termed metaplasticity. This study is designed to examine the plasticity and metaplasticity in the lateral perforant path of rat. Methods Field potential was measured with different priming and conditioning stimulation protocols. Results Ten-hertz priming, which does not affect basal synaptic transmission, caused a dramatic reduction in subsequent LTP at lateral perforant path synapses in vitro, and the reduced LTP lasted for at least 2 h. The LTD was unaffected. The reduction of LTP in the lateral perforant path was also readily induced by applying priming antidromically at the mossy fibers. Conclusion Priming with 10 Hz, which is within a frequency range observed during physiological activity, can cause potent,long-lasting inhibition of LTP, but not LTD. This form of metaplasticity adds a layer of complexity to the activity-dependent modification of synapses within the dentate gyrus.

  9. Effects of Ethanol Exposure during Distinct Periods of Brain Development on Hippocampal Synaptic Plasticity

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    Brian R. Christie

    2013-07-01

    Full Text Available Fetal alcohol spectrum disorders occur when a mother drinks during pregnancy and can greatly influence synaptic plasticity and cognition in the offspring. In this study we determined whether there are periods during brain development that are more susceptible to the effects of ethanol exposure on hippocampal synaptic plasticity. In particular, we evaluated how the ability to elicit long-term potentiation (LTP in the hippocampal dentate gyrus (DG was affected in young adult rats that were exposed to ethanol during either the 1st, 2nd, or 3rd trimester equivalent. As expected, the effects of ethanol on young adult DG LTP were less severe when exposure was limited to a particular trimester equivalent when compared to exposure throughout gestation. In males, ethanol exposure during the 1st, 2nd or 3rd trimester equivalent did not significantly reduce LTP in the DG. In females, ethanol exposure during either the 1st or 2nd trimester equivalents did not impact LTP in early adulthood, but following exposure during the 3rd trimester equivalent alone, LTP was significantly increased in the female DG. These results further exemplify the disparate effects between the ability to elicit LTP in the male and female brain following perinatal ethanol exposure (PNEE.

  10. Nitric oxide signaling exerts bidirectional effects on plasticity inductions in amygdala.

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    Shin, Ryong-Moon; Higuchi, Makoto; Suhara, Tetsuya

    2013-01-01

    It has been well known that long-term potentiation (LTP) of synaptic transmission in the lateral nucleus of the amygdala (LA) constitutes an essential cellular mechanism contributing to encoding of conditioned fear. Nitric oxide (NO), produced by activation of the postsynaptic N-methyl-D-aspartate receptors (NMDAR) in thalamic input to the LA, has been thought to promote LTP, contributing to the establishment of conditioned fear. However, it is not known whether and how NO, released from cortical input to the LA, plays the role on the plasticity induction and fear memory. Here we report that the diffusion of NO, released in response to activation of presynaptic NMDAR on cortical afferent fibers in the LA, could suppress heterosynaptically a form of presynaptic kainate receptor (KAR) dependent LTP (pre-LTP) in thalamic input, which was induced by low-frequency presynaptic stimuli without postsynaptic depolarization. We also confirmed that NO, produced by activation of postsynaptic NMDAR in thalamic input, can promote postsynaptic NMDAR-dependent LTP (post-LTP), which was induced by pairing protocol. These LTPs were occluded following fear conditioning, indicating that they could contribute to encoding of conditioned fear memory. However, their time courses are different; Post-LTP was more rapidly formed than pre-LTP in the course of fear conditioning. NO, produced by activation of presynaptic NMDAR in cortical input and postsynaptic NMDAR in thalamic input, may control conditioned fear by suppressing pre-LTP and promoting post-LTP, respectively, in thalamic input to the LA. PMID:24086360

  11. Nitric oxide signaling exerts bidirectional effects on plasticity inductions in amygdala.

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    Ryong-Moon Shin

    Full Text Available It has been well known that long-term potentiation (LTP of synaptic transmission in the lateral nucleus of the amygdala (LA constitutes an essential cellular mechanism contributing to encoding of conditioned fear. Nitric oxide (NO, produced by activation of the postsynaptic N-methyl-D-aspartate receptors (NMDAR in thalamic input to the LA, has been thought to promote LTP, contributing to the establishment of conditioned fear. However, it is not known whether and how NO, released from cortical input to the LA, plays the role on the plasticity induction and fear memory. Here we report that the diffusion of NO, released in response to activation of presynaptic NMDAR on cortical afferent fibers in the LA, could suppress heterosynaptically a form of presynaptic kainate receptor (KAR dependent LTP (pre-LTP in thalamic input, which was induced by low-frequency presynaptic stimuli without postsynaptic depolarization. We also confirmed that NO, produced by activation of postsynaptic NMDAR in thalamic input, can promote postsynaptic NMDAR-dependent LTP (post-LTP, which was induced by pairing protocol. These LTPs were occluded following fear conditioning, indicating that they could contribute to encoding of conditioned fear memory. However, their time courses are different; Post-LTP was more rapidly formed than pre-LTP in the course of fear conditioning. NO, produced by activation of presynaptic NMDAR in cortical input and postsynaptic NMDAR in thalamic input, may control conditioned fear by suppressing pre-LTP and promoting post-LTP, respectively, in thalamic input to the LA.

  12. Spike timing regulation on the millisecond scale by distributed synaptic plasticity at the cerebellum input stage: a simulation study

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    Jesus A Garrido

    2013-05-01

    Full Text Available The way long-term synaptic plasticity regulates neuronal spike patterns is not completely understood. This issue is especially relevant for the cerebellum, which is endowed with several forms of long-term synaptic plasticity and has been predicted to operate as a timing and a learning machine. Here we have used a computational model to simulate the impact of multiple distributed synaptic weights in the cerebellar granular layer network. In response to mossy fiber bursts, synaptic weights at multiple connections played a crucial role to regulate spike number and positioning in granule cells. The weight at mossy fiber to granule cell synapses regulated the delay of the first spike and the weight at mossy fiber and parallel fiber to Golgi cell synapses regulated the duration of the time-window during which the first-spike could be emitted. Moreover, the weights of synapses controlling Golgi cell activation regulated the intensity of granule cell inhibition and therefore the number of spikes that could be emitted. First spike timing was regulated with millisecond precision and the number of spikes ranged from 0 to 3. Interestingly, different combinations of synaptic weights optimized either first-spike timing precision or spike number, efficiently controlling transmission and filtering properties. These results predict that distributed synaptic plasticity regulates the emission of quasi-digital spike patterns on the millisecond time scale and allows the cerebellar granular layer to flexibly control burst transmission along the mossy fiber pathway.

  13. Multiplicative gain modulation arising from inhibitory synaptic plasticity in the cerebellar nuclei

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    Dimitris Bampasakis

    2014-03-01

    Full Text Available Neurons use the rate of action potentials to encode sensory variables. This makes the output rate as a function of input, also known as input-output (I–O relationship, a core computational function in neuronal processing. The introduction, or increase, of a modulatory input, can transform this function in multiple ways: additive transformations result in a shift, and multiplicative transformations in a change of slope of the I–O relationship. This slope change is known as gain modulation, and it can implement important forms of neural computation such as coordinate transformations. Gain modulation can be found in a wide range of brain systems, including the cerebellum, where it can be enabled by synaptic plasticity at both excitatory and inhibitory synapses. We use a realistic, conductance based, multi-compartmental model of a cerebellar nucleus (CN neuron, to investigate the determinants of gain modulation mediated by synaptic plasticity. In particular, we are interested in the effect of short term depression (STD at the inhibitory synapse from Purkinje cells (PCs to CN neurons. Considering the inhibitory PC input as the driving input, we compare the I–O relationship of the CN neuron in the presence and absence of STD for 20 Hz of excitatory synaptic input from mossy fibers (MFs, and find that STD introduces a gain change, changing the slope of the I–O function. We then proceed to compare the transformation performed by the increase of the modulatory input from 20 to 50 Hz, in the presence and absence of STD. We find that the presence of STD in the inhibitory synapse introduces a multiplicative component in the transformation performed by the excitatory input, an effect that persists for different levels of STD, and various combinations of regularity and synchronicity in the input.

  14. BDNF interacts with endocannabinoids to regulate cocaine-induced synaptic plasticity in mouse midbrain dopamine neurons.

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    Zhong, Peng; Liu, Yong; Hu, Ying; Wang, Tong; Zhao, Yong-ping; Liu, Qing-song

    2015-03-11

    Brain-derived neurotrophic factor (BDNF) and endocannabinoids (eCBs) have been individually implicated in behavioral effects of cocaine. The present study examined how BDNF-eCB interaction regulates cocaine-induced synaptic plasticity in the ventral tegmental area and behavioral effects. We report that BDNF and selective tyrosine kinase receptor B (TrkB) agonist 7,8-dihydroxyflavone (DHF) activated the TrkB receptor to facilitate two forms of eCB-mediated synaptic depression, depolarization-induced suppression of inhibition (DSI), and long-term depression (I-LTD) of IPSCs in ventral tegmental area dopamine neurons in mouse midbrain slices. The facilitation appears to be mediated by an increase in eCB production via phospholipase Cγ pathway, but not by an increase in CB1 receptor responsiveness or a decrease in eCB hydrolysis. Using Cre-loxP technology to specifically delete BDNF in dopamine neurons, we showed that eCB-mediated I-LTD, cocaine-induced reduction of GABAergic inhibition, and potentiation of glutamatergic excitation remained intact in wild-type control mice, but were impaired in BDNF conditional knock-out mice. We also showed that cocaine-induced conditioned place preference was attenuated in BDNF conditional knock-out mice, in vivo pretreatments with DHF before place conditioning restored cocaine conditioned place preference in these mice, and the behavioral effect of DHF was blocked by a CB₁ receptor antagonist. Together, these results suggest that BDNF in dopamine neurons regulates eCB responses, cocaine-induced synaptic plasticity, and associative learning. PMID:25762688

  15. Histone acetylation in the olfactory bulb of young rats facilitates aversive olfactory learning and synaptic plasticity.

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    Wang, Y-J; Okutani, F; Murata, Y; Taniguchi, M; Namba, T; Kaba, H

    2013-03-01

    Epigenetic mechanisms play an important role in memory formation and synaptic plasticity. Specifically, histone-associated heterochromatin undergoes changes in structure during the early stages of long-term memory formation. In keeping with the classical conditioning paradigm, young rats have been shown to exhibit aversion to an odor stimulus initially presented during foot shock. We previously showed that synaptic plasticity at the dendrodendritic synapses between mitral and granule cells in the olfactory bulb (OB) underlies this aversive olfactory learning. However, the epigenetic mechanisms involved are not well characterized. Therefore, we examined whether intrabulbar infusion of trichostatin A (TSA), a histone deacetylase inhibitor, facilitates olfactory learning in young rats. TSA infusion during odor-shock training enhanced a conditioned odor aversion in a dose-dependent manner and prolonged the learned aversion. Western blot and immunohistochemical analyses showed that the level of histone H4 acetylation significantly increased until 4 h after odor-shock training in both mitral and granule cells in the OB, whereas histone H3 acetylation returned to the control level at 2 h after the training. We also obtained evidence that TSA infusion elevated acetylation of histone H4 or H3. Furthermore, in vitro electrophysiological analysis using slices of the OB revealed that application of TSA significantly enhanced the long-term potentiation induced in synaptic transmission from mitral to granule cells at dendrodendritic synapses. Taken together, these results provide evidence that histone H4 and H3 acetylation in the OB is an epigenetic mechanism associated with aversive olfactory learning in young rats.

  16. Impaired hippocampal synaptic plasticity and NR2A/2B expression ratio in remifentanil withdrawal rats.

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    Wang, Yi-Yi; Liu, Shichang; Zhang, Nan; Yang, Jing; Zhang, Yinguo

    2016-03-01

    Remifentanil is a kind of synthetic opioid which has gained wide clinical acceptance by anesthesiologists. In this study, we attempted to test whether withdrawal effects on learning mechanisms can be triggered by repeated low-dose remifentanil treatment. Male Sprague-Dawley (SD) rats were subjected to remifentanil (50μg/kgs.c.) twice per day at 12h intervals for 15 days. When the animals of remifentanil group were withdrawn from remifentanil at 10h after the last injection, changes in open field test, Morris water maze test (MWM) and synaptic efficacy were examined in each group. We demonstrated that repeated exposure to 50μg/kg remifentanil produced enhanced locomotor activity indicating that a remifentanil addiction animal model in rats was established. MWM results showed that exposure to remifentanil had no influence on the spatial cognition. After withdrawal of remifentanil rats showed impaired spatial cognition. In electrophysiology test, remifentanil group rats showed a trend for a rightward shift of input/output relationship and significant deficits in maintenance of STP and LTP. Immunohistochemistry results demonstrated increased NR2A/NR2B ratio that should be included depression of LTP. In the whole-cell patch-clamp recording, after elimination from remifentanil incubation, mEPSC frequency was down regulated in hippocampal CA1 neurons, indicating that basal synaptic transmission were affected by remifentanil withdrawal. Taken together, the current findings demonstrate that the remifentanil withdrawn rats exhibit obvious impairment of hippocampus-dependent memory and synaptic plasticity. Increased hippocampal NR2A/NR2B expression ratio and the changes of basal synaptic transmission may participate in the impairment of LTP. PMID:26777139

  17. Translational control by eIF2α kinases in long-lasting synaptic plasticity and long-term memory.

    Science.gov (United States)

    Trinh, Mimi A; Klann, Eric

    2013-10-01

    Although the requirement for new protein synthesis in synaptic plasticity and memory has been well established, recent genetic, molecular, electrophysiological, and pharmacological studies have broadened our understanding of the translational control mechanisms that are involved in these processes. One of the critical translational control points mediating general and gene-specific translation depends on the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) by four regulatory kinases. Here, we review the literature highlighting the important role for proper translational control via regulation of eIF2α phosphorylation by its kinases in long-lasting synaptic plasticity and long-term memory.

  18. Strain-dependent variations in spatial learning and in hippocampal synaptic plasticity in the dentate gyrus of freely behaving rats

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    Denise eManahan-Vaughan

    2011-03-01

    Full Text Available Hippocampal synaptic plasticity is believed to comprise the cellular basis for spatial learning. Strain-dependent differences in synaptic plasticity in the CA1 region have been reported. However, it is not known whether these differences extend to other synapses within the trisynaptic circuit, although there is evidence for morphological variations within that path. We investigated whether Wistar and Hooded Lister (HL rat strains express differences in synaptic plasticity in the dentate gyrus in vivo. We also explored whether they exhibit differences in the ability to engage in spatial learning in an 8-arm radial maze. Basal synaptic transmission was stable over a 24h period in both rat strains, and the input-output relationship of both strains was not significantly different. Paired-pulse analysis revealed significantly less paired-pulse facilitation in the Hooded Lister strain when pulses were given 40-100 msec apart. Low frequency stimulation at 1Hz evoked long-term depression (>24h in Wistar and short-term depression (<2h in HL rats; 200Hz stimulation induced long-term potentiation (>24h in Wistar, and a transient, significantly smaller potentiation (<1h in HL rats, suggesting that HL rats have higher thresholds for expression of persistent synaptic plasticity. Training for 10d in an 8-arm radial maze revealed that HL rats master the working memory task faster than Wistar rats, although both strains show an equivalent performance by the end of the trial period. HL rats also perform more efficiently in a double working and reference memory task. On the other hand, Wistar rats show better reference memory performance on the final (8-10 days of training. Wistar rats were less active and more anxious than HL rats.These data suggest that strain-dependent variations in hippocampal synaptic plasticity occur in different hippocampal synapses. A clear correlation with differences in spatial learning is not evident however.

  19. High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity.

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    Zhigang Liu

    Full Text Available High-fat diet (HFD-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group or a HFD (60% of calorie from fat; HFD group for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a a significant decrease of insulin receptor substrate (IRS-1 phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment; this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a an inactivation of the IRS-1 and, consequentially, (b a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c a suppression of the ERK/CREB pathway, and (d a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity. It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts

  20. Taurine content in different brain structures during ageing: effect on hippocampal synaptic plasticity.

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    Suárez, Luz M; Muñoz, María-Dolores; Martín Del Río, Rafael; Solís, José M

    2016-05-01

    A reduction in taurine content accompanies the ageing process in many tissues. In fact, the decline of brain taurine levels has been associated with cognitive deficits whereas chronic administration of taurine seems to ameliorate age-related deficits such as memory acquisition and retention. In the present study, using rats of three age groups (young, adult and aged) we determined whether the content of taurine and other amino acids (glutamate, serine, glutamine, glycine, alanine and GABA) was altered during ageing in different brain areas (cerebellum, cortex and hippocampus) as well non-brain tissues (heart, kidney, liver and plasma). Moreover, using hippocampal slices we tested whether ageing affects synaptic function and plasticity. These parameters were also determined in aged rats fed with either taurine-devoid or taurine-supplemented diets. With age, we found heterogeneous changes in amino acid content depending on the amino acid type and the tissue. In the case of taurine, its content was reduced in the cerebellum of adult and aged rats, but it remained unchanged in the hippocampus, cortex, heart and liver. The synaptic response amplitude decreased in aged rats, although the late phase of long-term synaptic potentiation (late-LTP), a taurine-dependent process, was not altered. Our study highlights the stability of taurine content in the hippocampus during ageing regardless of whether taurine was present in the diet, which is consistent with the lack of changes detected in late-LTP. These results indicate that the beneficial effects of taurine supplementation might be independent of the replenishment of taurine stores. PMID:26803657

  1. Impaired synaptic plasticity in the prefrontal cortex of mice with developmentally decreased number of interneurons.

    Science.gov (United States)

    Konstantoudaki, X; Chalkiadaki, K; Tivodar, S; Karagogeos, D; Sidiropoulou, K

    2016-05-13

    Interneurons are inhibitory neurons, which protect neural tissue from excessive excitation. They are interconnected with glutamatergic pyramidal neurons in the cerebral cortex and regulate their function. Particularly in the prefrontal cortex (PFC), interneurons have been strongly implicated in regulating pathological states which display deficits in the PFC. The aim of this study is to investigate the adaptations in the adult glutamatergic system, when defects in interneuron development do not allow adequate numbers of interneurons to reach the cerebral cortex. To this end, we used a mouse model that displays ∼50% fewer cortical interneurons due to the Rac1 protein loss from Nkx2.1/Cre expressing cells (Rac1 conditional knockout (cKO) mice), to examine how the developmental loss of interneurons may affect basal synaptic transmission, synaptic plasticity and neuronal morphology in the adult PFC. Despite the decrease in the number of interneurons, basal synaptic transmission, as examined by recording field excitatory postsynaptic potentials (fEPSPs) from layer II networks, is not altered in the PFC of Rac1 cKO mice. However, there is decreased paired-pulse ratio (PPR) and decreased long-term potentiation (LTP), in response to tetanic stimulation, in the layer II PFC synapses of Rac1 cKO mice. Furthermore, expression of N-methyl-d-aspartate (NMDA) subunits is decreased and dendritic morphology is altered, changes that could underlie the decrease in LTP in the Rac1 cKO mice. Finally, we find that treating Rac1 cKO mice with diazepam in early postnatal life can reverse changes in dendritic morphology observed in non-treated Rac1 cKO mice. Therefore, our data show that disruption in GABAergic inhibition alters glutamatergic function in the adult PFC, an effect that could be reversed by enhancement of GABAergic function during an early postnatal period. PMID:26926965

  2. A novel fibroblast growth factor receptor family member promotes neuronal outgrowth and synaptic plasticity in aplysia.

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    Pollak, Daniela D; Minh, Bui Quang; Cicvaric, Ana; Monje, Francisco J

    2014-11-01

    Fibroblast Growth Factor (FGF) Receptors (FGFRs) regulate essential biological processes, including embryogenesis, angiogenesis, cellular growth and memory-related long-term synaptic plasticity. Whereas canonical FGFRs depend exclusively on extracellular Immunoglobulin (Ig)-like domains for ligand binding, other receptor types, including members of the tropomyosin-receptor-kinase (Trk) family, use either Ig-like or Leucine-Rich Repeat (LRR) motifs, or both. Little is known, however, about the evolutionary events leading to the differential incorporation of LRR domains into Ig-containing tyrosine kinase receptors. Moreover, although FGFRs have been identified in many vertebrate species, few reports describe their existence in invertebrates. Information about the biological relevance of invertebrate FGFRs and evolutionary divergences between them and their vertebrate counterparts is therefore limited. Here, we characterized ApLRRTK, a neuronal cell-surface protein recently identified in Aplysia. We unveiled ApLRRTK as the first member of the FGFRs family deprived of Ig-like domains that instead contains extracellular LRR domains. We describe that ApLRRTK exhibits properties typical of canonical vertebrate FGFRs, including promotion of FGF activity, enhancement of neuritic outgrowth and signaling via MAPK and the transcription factor CREB. ApLRRTK also enhanced the synaptic efficiency of neurons known to mediate in vivo memory-related defensive behaviors. These data reveal a novel molecular regulator of neuronal function in invertebrates, provide the first evolutionary linkage between LRR proteins and FGFRs and unveil an unprecedented mechanism of FGFR gene diversification in primeval central nervous systems.

  3. Functional improvement after motor training is correlated with synaptic plasticity in rat thalamus.

    Science.gov (United States)

    Ding, Yuchuan; Li, Jie; Lai, Qin; Azam, Salman; Rafols, José A; Diaz, Fernando G

    2002-12-01

    The goals of this study were to determine whether functional outcome after motor training in rats was linked to synaptic plasticity in thalamus, and whether the Rota-rod apparatus, widely used to test motor function, could be used as an easy and quantitative motor skill training procedure. Adult female Sprague-Dawley rats (n = 39) were evaluated under three training conditions: 1. Movement requiring balance and coordination skills on Rota-rod; 2. simple exercise on treadmill; 3. nontrained controls. Motor function was evaluated by a series of motor tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and 14 or 28 days after training procedure. Synaptic strength in brain was assessed by synaptophysin immunocytochemistry. After 14 days of training, Rota-rod-trained animals significantly (p exercises on the treadmill did not show a significantly improved performance on most motor tasks, except for an improvement in foot fault placing. Intensive synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus in Rota-rod-trained rats at 14 and 28 days, and in treadmill-trained rats at 28 days. The data suggested that functional outcome is effectively improved by motor skill training rather than by simple exercises, and this may be related, at least partially, to uniquely lateralized synaptogenesis in the thalamus. Both Rota-rod and treadmill could be quantitatively used in rats for motor training of different complexity. PMID:12500709

  4. Protective effect of tetrahydroxy stilbene glucoside on learning and memory by regulating synaptic plasticity

    Institute of Scientific and Technical Information of China (English)

    Hong-bo Luo; Yun Li; Zun-jing Liu; Li Cao; Zhi-qiang Zhang; Yong Wang; Xiao-yan Zhang; Zhao Liu; Xiang-qun Shi

    2016-01-01

    Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer’s disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B (NR2B) expression. An APP695V7171 transgenic mouse model of Alzheimer’s disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas-trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These ifndings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer’s disease.

  5. Glutathione restores the mechanism of synaptic plasticity in aged mice to that of the adult.

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    Julie M Robillard

    Full Text Available Glutathione (GSH, the major endogenous antioxidant produced by cells, can modulate the activity of N-methyl-D-aspartate receptors (NMDARs through its reducing functions. During aging, an increase in oxidative stress leads to decreased levels of GSH in the brain. Concurrently, aging is characterized by calcium dysregulation, thought to underlie impairments in hippocampal NMDAR-dependent long-term potentiation (LTP, a form of synaptic plasticity thought to represent a cellular model for memory. Here we show that orally supplementing aged mice with N-acetylcysteine, a precursor for the formation of glutathione, reverses the L-type calcium channel-dependent LTP seen in aged animals to NMDAR-dependent LTP. In addition, introducing glutathione in the intrapipette solution during whole-cell recordings restores LTP obtained in whole-cell conditions in the aged hippocampus. We conclude that aging leads to a reduced redox potential in hippocampal neurons, triggering impairments in LTP.

  6. Self healing of open circuit faults: With active re-configurability and mimicry of synaptic plasticity

    Science.gov (United States)

    Yaswant, Vaddi; Kumar, Amit; Sambandan, Sanjiv

    2016-07-01

    We discuss the self-repair of open faults in circuits using electrically conductive particles dispersed in an insulating fluid. The repair is triggered by the electric field developed across the open circuit in a current carrying interconnect and results in the formation of a bridge of particles across the gap. We illustrate and model the dynamics of the resistance of the self-healed route, Rb, in low field conditions. Furthermore, active control of Rb and active re-wiring are also demonstrated. Considering Rb to be akin to weights between nodes, the formation and re-wiring of routes and the control of Rb mimic synaptic plasticity in biological systems and open interesting possibilities for computing.

  7. Different Compartments of Apical CA1 Dendrites Have Different Plasticity Thresholds for Expressing Synaptic Tagging and Capture

    Science.gov (United States)

    Sajikumar, Sreedharan; Korte, Martin

    2011-01-01

    The consolidation process from short- to long-term memory depends on the type of stimulation received from a specific neuronal network and on the cooperativity and associativity between different synaptic inputs converging onto a specific neuron. We show here that the plasticity thresholds for inducing LTP are different in proximal and distal…

  8. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala.

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    Melissa S Monsey

    Full Text Available Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM is enhanced, while short-term memory (STM is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA.

  9. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala.

    Science.gov (United States)

    Monsey, Melissa S; Ota, Kristie T; Akingbade, Irene F; Hong, Ellie S; Schafe, Glenn E

    2011-01-01

    Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA.

  10. Spinal motoneuron synaptic plasticity after axotomy in the absence of inducible nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Zanon Renata G

    2010-05-01

    Full Text Available Abstract Background Astrocytes play a major role in preserving and restoring structural and physiological integrity following injury to the nervous system. After peripheral axotomy, reactive gliosis propagates within adjacent spinal segments, influenced by the local synthesis of nitric oxide (NO. The present work investigated the importance of inducible nitric oxide synthase (iNOS activity in acute and late glial responses after injury and in major histocompatibility complex class I (MHC I expression and synaptic plasticity of inputs to lesioned alpha motoneurons. Methods In vivo analyses were carried out using C57BL/6J-iNOS knockout (iNOS-/- and C57BL/6J mice. Glial response after axotomy, glial MHC I expression, and the effects of axotomy on synaptic contacts were measured using immunohistochemistry and transmission electron microscopy. For this purpose, 2-month-old animals were sacrificed and fixed one or two weeks after unilateral sciatic nerve transection, and spinal cord sections were incubated with antibodies against classical MHC I, GFAP (glial fibrillary acidic protein - an astroglial marker, Iba-1 (an ionized calcium binding adaptor protein and a microglial marker or synaptophysin (a presynaptic terminal marker. Western blotting analysis of MHC I and nNOS expression one week after lesion were also performed. The data were analyzed using a two-tailed Student's t test for parametric data or a two-tailed Mann-Whitney U test for nonparametric data. Results A statistical difference was shown with respect to astrogliosis between strains at the different time points studied. Also, MHC I expression by iNOS-/- microglial cells did not increase at one or two weeks after unilateral axotomy. There was a difference in synaptophysin expression reflecting synaptic elimination, in which iNOS-/- mice displayed a decreased number of the inputs to alpha motoneurons, in comparison to that of C57BL/6J. Conclusion The findings herein indicate that i

  11. Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia.

    Science.gov (United States)

    Wang, Manqi; Wang, Qian; Whim, Matthew D

    2016-05-24

    During fasting, activation of the counter-regulatory response (CRR) prevents hypoglycemia. A major effector arm is the autonomic nervous system that controls epinephrine release from adrenal chromaffin cells and, consequently, hepatic glucose production. However, whether modulation of autonomic function determines the relative strength of the CRR, and thus the ability to withstand food deprivation and maintain euglycemia, is not known. Here we show that fasting leads to altered transmission at the preganglionic → chromaffin cell synapse. The dominant effect is a presynaptic, long-lasting increase in synaptic strength. Using genetic and pharmacological approaches we show this plasticity requires neuropeptide Y, an adrenal cotransmitter and the activation of adrenal Y5 receptors. Loss of neuropeptide Y prevents a fasting-induced increase in epinephrine release and results in hypoglycemia in vivo. These findings connect plasticity within the sympathetic nervous system to a physiological output and indicate the strength of the final synapse in this descending pathway plays a decisive role in maintaining euglycemia. PMID:27092009

  12. The Role of GluK4 in Synaptic Plasticity and Affective Behavior in Mice

    Science.gov (United States)

    Catches, Justin Samuel

    Kainate receptors (KARs) are glutamate-gated ion channels that signal through both ionotropic and metabotropic pathways (Contractor et al., 2011). Combinations of five KAR subunits (GluK1-5) form tetrameric receptors with GluK1, GluK2, and GluK3 able to form functional homomeric channels. The high-affinity subunits, GluK4 and GluK5, do not form homomeric channels but modify the properties of heteromeric receptors. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs modulate synaptic plasticity. In this study, ablation of Grik4, which encodes GluK4, in mice reduced KAR synaptic currents and altered activation properties of postsynaptic receptors but left two forms of presynaptic short-term plasticity intact. Disruption of both Grik4 and Grik5 caused complete loss of the postsynaptic ionotropic KAR current and impaired presynaptic frequency facilitation. Additionally, KAR surface expression was altered at pre- and postsynaptic sites at the MF synapse. Despite the loss of ionotropic signaling, KAR-mediated inhibition of the slow afterhyperpolarization current, which is dependent on metabotropic signaling, was intact in CA3 neurons. Long-term potentiation at the MF-CA3 synapse was reduced, likely through a loss of KAR modulation of excitability of the presynaptic MF axons. Genetic variants in the human GRIK4 gene alter the susceptibility for affective disorders (Bloss and Hunter, 2010). We found that ablation of Grik4 in mice resulted in reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, and in two anxiogenic tests, marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim, a test of learned helplessness used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting

  13. Streptavidin-conjugated CdSe/ZnS quantum dots impaired synaptic plasticity and spatial memory process

    Energy Technology Data Exchange (ETDEWEB)

    Gao Xiaoyan [Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf (Germany); Tang Mingliang [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (China); Li Zhifeng; Zha Yingying [University of Science and Technology of China, CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences (China); Cheng Guosheng [Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (China); Yin Shuting [Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf (Germany); Chen Jutao; Ruan Diyun; Chen Lin; Wang Ming, E-mail: wming@ustc.edu.cn [University of Science and Technology of China, CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences (China)

    2013-04-15

    Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output (I/O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats' spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.

  14. Streptavidin-conjugated CdSe/ZnS quantum dots impaired synaptic plasticity and spatial memory process

    International Nuclear Information System (INIS)

    Studies reported that quantum dots (QDs), as a novel probe, demonstrated a promising future for in vivo imaging, but also showed potential toxicity. This study is mainly to investigate in vivo response in the central nervous system (CNS) after exposure to QDs in a rat model of synaptic plasticity and spatial memory. Adult rats were exposed to streptavidin-conjugated CdSe/ZnS QDs (Qdots 525, purchased from Molecular Probes Inc.) by intraperitoneal injection for 7 days, followed by behavioral, electrophysiological, and biochemical examinations. The electrophysiological results show that input/output (I/O) functions were increased, while the peak of paired-pulse reaction and long-term potentiation were decreased after QDs insult, indicating synaptic transmission was enhanced and synaptic plasticity in the hippocampus was impaired. Meanwhile, behavioral experiments provide the evidence that QDs could impair rats’ spatial memory process. All the results present evidences of interference of synaptic transmission and plasticity in rat hippocampal dentate gyrus area by QDs insult and suggest potential adverse issues which should be considered in QDs applications.

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

    Science.gov (United States)

    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.

  16. A Recipe for Bidirectional Motor Learning: Using Inhibition to Cook Plasticity in the Vestibular Nuclei

    OpenAIRE

    Medina, Javier F.

    2010-01-01

    In this issue of Neuron, McElvain et al. demonstrate for the first time plasticity at the synapse between vestibular nerve afferents and their postsynaptic targets in the medial vestibular nuclei. This new type of plasticity, which is gated by inhibition, is well suited to drive motor learning during adaptation of the vestibulo-ocular reflex.

  17. Nitric Oxide Signaling Exerts Bidirectional Effects on Plasticity Inductions in Amygdala

    OpenAIRE

    Shin, Ryong-Moon; Higuchi, Makoto; Suhara, Tetsuya

    2013-01-01

    It has been well known that long-term potentiation (LTP) of synaptic transmission in the lateral nucleus of the amygdala (LA) constitutes an essential cellular mechanism contributing to encoding of conditioned fear. Nitric oxide (NO), produced by activation of the postsynaptic N-methyl-D-aspartate receptors (NMDAR) in thalamic input to the LA, has been thought to promote LTP, contributing to the establishment of conditioned fear. However, it is not known whether and how NO, released from cort...

  18. Synapse-specific stabilization of plasticity processes: the synaptic tagging and capture hypothesis revisited 10 years later.

    Science.gov (United States)

    Barco, Angel; Lopez de Armentia, Mikel; Alarcon, Juan M

    2008-01-01

    A decade ago, the synaptic tagging hypothesis was proposed to explain how newly synthesized plasticity products can be specifically targeted to active synapses. A growing number of studies have validated the seminal findings that gave rise to this model, as well as contributed to unveil and expand the range of mechanisms underlying late-associativity and neuronal computation. Here, we will review what it was learnt during this past decade regarding the cellular and molecular mechanisms underlying synaptic tagging and synaptic capture. The accumulated experimental evidence has widened the theoretical framework set by the synaptic tagging and capture (STC) model and introduced concepts that were originally considered part of alternative models for explaining synapse-specific long-term potentiation (LTP). As a result, we believe that the STC model, now improved and expanded with these new ideas and concepts, still represents the most compelling hypothesis to explain late-associativity in synapse-specific plasticity processes. We will also discuss the impact of this model in our view of the integrative capability of neurons and associative learning. PMID:18281094

  19. Effects of decreased inhibition on synaptic plasticity and dendritic morphology in the juvenile prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Xanthippi Konstantoudaki

    2014-03-01

    Full Text Available Excitation-inhibition balance is critical for maintaining proper functioning of the cerebral cortex, as evident from electrophysiological and modeling studies, and it is also important for animal behavior (Yizhar et al., 2011. In the cerebral cortex, excitation is provided by glutamate release from pyramidal neurons, while inhibition is provided by GABA release from several types of interneurons. Many neuropsychiatric disorders, such as epilepsy, anxiety, schizophrenia and autism exhibit an imbalance between the excitatory and inhibitory mechanisms of cortical circuits within key brain regions as prefrontal cortex or hippocampus, primarily through dysfunctions in the inhibitory system (Lewis, Volk, & Hashimoto, 2003; Marín, 2012 Given the significant role of GABAergic inhibition in shaping proper function of the cerebral cortex, we used a mouse model of developmentally decreased GABAergic inhibition in order to examine its effects in network properties, namely basal synaptic transmission, synaptic plasticity and dendritic morphology of pyramidal neurons. For our study, we used mice (postnatal day 20-30 in which the Rac1 protein was deleted from Nkx2.1-expressing neurons (Vidaki et al., 2012, (Rac1fl/flNkx2.1 +/cre referred as Rac1 KO mice, and heterozygous (Rac1+/flNkx2.1 +/cre or control (Rac1+/flNkx2.1 +/+ mice. The specific ablation of Rac1 protein from NKx2.1-expressing MGE-derived progenitors leads to a perturbation of their cell cycle exit resulting in decreased number of interneurons in the cortex(Vidaki et al, 2012. We prepared brain slices from the prefrontal cortex and recorded field excitatory postsynaptic potentials (fEPSPs from layer II neurons while stimulating axons in layer II. We find that the evoked fEPSPs are decreased in Rac1 KO mice compared to Rac1 heterozygous or control mice. This could suggest that the decreased GABAergic inhibition causes network alterations that result in reduced glutamatergic function. Furthermore

  20. Dopamine-dependent synaptic plasticity in an amygdala inhibitory circuit controls fear memory expression.

    Science.gov (United States)

    Lee, Joo Han; Kim, Joung-Hun

    2016-01-01

    Of the numerous events that occur in daily life, we readily remember salient information, but do not retain most less-salient events for a prolonged period. Although some of the episodes contain putatively emotional aspects, the information with lower saliency is rarely stored in neural circuits via an unknown mechanism. We provided substantial evidence indicating that synaptic plasticity in the dorsal ITC of amygdala allows for selective storage of salient emotional experiences, while it deters less-salient experience from entering long-term memory. After activation of D4R or weak fear conditioning, STDP stimulation induces LTD in the LA-ITC synapses. This form of LTD is dependent upon presynaptic D4R, and is likely to result from enhancement of GABA release. Both optogenetic abrogation of LTD and ablation of D4R at the dorsal ITC in vivo lead to heightened and over-generalized fear responses. Finally, we demonstrated that LTD was impaired at the dorsal ITC of PTSD model mice, which suggests that maladaptation of GABAergic signaling and the resultant LTD impairment contribute to the endophenotypes of PTSD. PMID:26674344

  1. Synaptic plasticity in the acoustic startle pathway: the neuronal basis for short-term habituation?

    Science.gov (United States)

    Weber, Maruschka; Schnitzler, Hans-Ulrich; Schmid, Susanne

    2002-10-01

    The aim of the present study was to analyse the cellular mechanism underlying short-term habituation of the acoustic startle response (ASR). We explored distinct synapses of the neuronal startle pathway in rat brain slices by patch-clamp recordings of giant neurons in the caudal pontine reticular formation. Presynaptic stimulation of auditory afferents by repeated bursts at 0.1 and 1 Hz led to an exponential decay of EPSC magnitudes. This homosynaptic depression (HSD) was reversible and repeatedly inducible after recovery. Many parameters of HSD in vitro match those of ASR habituation in vivo. The mechanisms underlying HSD are distinct from classical short-term plasticity: paired-pulse as well as paired-burst stimulation revealed a facilitation of the second EPSC, occurring in a much smaller time window up to interstimulus intervals of 200 ms. Pharmacological experiments demonstrated that HSD could be completely blocked by the group II and III metabotropic glutamate receptor antagonist MPPG. Similar results were obtained by CPPG, another group II and III antagonist. In contrast, HSD was not affected by the group I and II antagonist MCPG. We conclude that we found a form of synaptic depression in synapses within the primary startle pathway which correlates in many respects with short-term habituation of the ASR and which is presumably mediated by group III metabotropic glutamate receptors. PMID:12405993

  2. Role of the somatostatin system in contextual fear memory and hippocampal synaptic plasticity.

    Science.gov (United States)

    Kluge, Christian; Stoppel, Christian; Szinyei, Csaba; Stork, Oliver; Pape, Hans-Christian

    2008-04-01

    Somatostatin has been implicated in various cognitive and emotional functions, but its precise role is still poorly understood. Here, we have made use of mice with somatostatin deficiency, based upon genetic invalidation or pharmacologically induced depletion, and Pavlovian fear conditioning in order to address the contribution of the somatostatin system to associative fear memory. The results demonstrate an impairment of foreground and background contextual but not tone fear conditioning in mice with targeted ablation of the somatostatin gene. These deficits were associated with a decrease in long-term potentiation in the CA1 area of the hippocampus. Both the behavioral and the electrophysiological phenotypes were mimicked in wild-type mice through application of the somatostatin-depleting substance cysteamine prior to fear training, whereas no further deficits were observed upon application in the somatostatin null mutants. These results suggest that the somatostatin system plays a critical role in the acquisition of contextual fear memory, but not tone fear learning, and further highlights the role of hippocampal synaptic plasticity for information processing concerning contextual information.

  3. Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in mice.

    Science.gov (United States)

    Kusakari, Shinya; Saitow, Fumihito; Ago, Yukio; Shibasaki, Koji; Sato-Hashimoto, Miho; Matsuzaki, Yasunori; Kotani, Takenori; Murata, Yoji; Hirai, Hirokazu; Matsuda, Toshio; Suzuki, Hidenori; Matozaki, Takashi; Ohnishi, Hiroshi

    2015-05-01

    Shp2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) regulates neural cell differentiation. It is also expressed in postmitotic neurons, however, and mutations of Shp2 are associated with clinical syndromes characterized by mental retardation. Here we show that conditional-knockout (cKO) mice lacking Shp2 specifically in postmitotic forebrain neurons manifest abnormal behavior, including hyperactivity. Novelty-induced expression of immediate-early genes and activation of extracellular-signal-regulated kinase (Erk) were attenuated in the cerebral cortex and hippocampus of Shp2 cKO mice, suggestive of reduced neuronal activity. In contrast, ablation of Shp2 enhanced high-K(+)-induced Erk activation in both cultured cortical neurons and synaptosomes, whereas it inhibited that induced by brain-derived growth factor in cultured neurons. Posttetanic potentiation and paired-pulse facilitation were attenuated and enhanced, respectively, in hippocampal slices from Shp2 cKO mice. The mutant mice also manifested transient impairment of memory formation in the Morris water maze. Our data suggest that Shp2 contributes to regulation of Erk activation and synaptic plasticity in postmitotic forebrain neurons and thereby controls locomotor activity and memory formation.

  4. DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katherine E. Horn

    2013-01-01

    Full Text Available The transmembrane protein deleted in colorectal cancer (DCC and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP, intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.

  5. p38 MAPK Inhibition Improves Synaptic Plasticity and Memory in Angiotensin II-dependent Hypertensive Mice

    Science.gov (United States)

    Dai, Hai-long; Hu, Wei-yuan; Jiang, Li-hong; Li, Le; Gaung, Xue-feng; Xiao, Zhi-cheng

    2016-01-01

    The pathogenesis of hypertension-related cognitive impairment has not been sufficiently clarified, new molecular targets are needed. p38 MAPK pathway plays an important role in hypertensive target organ damage. Activated p38 MAPK was seen in AD brain tissue. In this study, we found that long-term potentiation (LTP) of hippocampal CA1 was decreased, the density of the dendritic spines on the CA1 pyramidal cells was reduced, the p-p38 protein expression in hippocampus was elevated, and cognitive function was impaired in angiotensin II-dependent hypertensive C57BL/6 mice. In vivo, using a p38 heterozygous knockdown mice (p38KI/+) model, we showed that knockdown of p38 MAPK in hippocampus leads to the improvement of cognitive function and hippocampal synaptic plasticity in angiotensin II-dependent p38KI/+ hypertensive mice. In vitro, LTP was improved in hippocampal slices from C57BL/6 hypertensive mice by treatment with p38MAPK inhibitor SKF86002. Our data demonstrated that p38 MAPK may be a potential therapeutic target for hypertension-related cognitive dysfunction. PMID:27283322

  6. Short-term synaptic plasticity can enhance weak signal detectability in nonrenewal spike trains.

    Science.gov (United States)

    Lüdtke, Niklas; Nelson, Mark E

    2006-12-01

    We study the encoding of weak signals in spike trains with interspike interval (ISI) correlations and the signals' subsequent detection in sensory neurons. Motivated by the observation of negative ISI correlations in auditory and electrosensory afferents, we assess the theoretical performance limits of an individual detector neuron receiving a weak signal distributed across multiple afferent inputs. We assess the functional role of ISI correlations in the detection process using statistical detection theory and derive two sequential likelihood ratio detector models: one for afferents with renewal statistics; the other for afferents with negatively correlated ISIs. We suggest a mechanism that might enable sensory neurons to implicitly compute conditional probabilities of presynaptic spikes by means of short-term synaptic plasticity. We demonstrate how this mechanism can enhance a postsynaptic neuron's sensitivity to weak signals by exploiting the correlation structure of the input spike trains. Our model not only captures fundamental aspects of early electrosensory signal processing in weakly electric fish, but may also bear relevance to the mammalian auditory system and other sensory modalities.

  7. Therapeutic hypothermia protects against ischemia-induced impairment of synaptic plasticity following juvenile cardiac arrest in sex-dependent manner.

    Science.gov (United States)

    Dietz, R M; Deng, G; Orfila, J E; Hui, X; Traystman, R J; Herson, P S

    2016-06-14

    Pediatric cardiac arrest (CA) often leads to poor neurologic outcomes, including deficits in learning and memory. The only approved treatment for CA is therapeutic hypothermia, although its utility in the pediatric population remains unclear. This study analyzed the effect of mild therapeutic hypothermia after CA in juvenile mice on hippocampal neuronal injury and the cellular model of learning and memory, termed long-term potentiation (LTP). Juvenile mice were subjected to cardiac arrest and cardiopulmonary resuscitation (CA/CPR) followed by normothermia (37°C) and hypothermia (30°C, 32°C). Histological injury of hippocampal CA1 neurons was performed 3days after resuscitation using hematoxylin and eosin (H&E) staining. Field excitatory post-synaptic potentials (fEPSPs) were recorded from acute hippocampal slices 7days after CA/CPR to determine LTP. Synaptic function was impaired 7days after CA/CPR. Mice exposed to hypothermia showed equivalent neuroprotection, but exhibited sexually dimorphic protection against ischemia-induced impairment of LTP. Hypothermia (32°C) protects synaptic plasticity more effectively in females, with males requiring a deeper level of hypothermia (30°C) for equivalent protection. In conclusion, male and female juvenile mice exhibit equivalent neuronal injury following CA/CPR and hypothermia protects both males and females. We made the surprising finding that juvenile mice have a sexually dimorphic response to mild therapeutic hypothermia protection of synaptic function, where males may need a deeper level of hypothermia for equivalent synaptic protection. PMID:27033251

  8. The interactive role of CB(1) and GABA(B) receptors in hippocampal synaptic plasticity in rats.

    Science.gov (United States)

    Nazari, Masoumeh; Komaki, Alireza; Karamian, Ruhollah; Shahidi, Siamak; Sarihi, Abdolrahman; Asadbegi, Masoumeh

    2016-01-01

    Long-term potentiation (LTP) of synaptic transmission is a cellular process underlying learning and memory. Cannabinoids are known to be powerful modulators of this kind of synaptic plasticity. Changes in GABAergic inhibition have also been shown to affect synaptic plasticity in the hippocampus. GABA receptor type B (GABAB) and cannabinoid receptor type 1 (CB1) exhibit overlapping anatomical localization in some brain areas including the hippocampus. CB1 and GABAB are also localized to the same cells and share a common signaling pathway in some brain areas. In this study, we examined the hippocampal effects of co-administrating AM251 and CGP55845, which are CB1 and GABAB antagonists, respectively, on LTP induction in the dentate gyrus (DG) of rats. LTP in the hippocampal area was induced by high-frequency stimulation (HFS) of the perforant path. Our results showed that HFS coupled with administration of the CB1 antagonist increased both the population spike (PS) amplitude and field excitatory post-synaptic potential (fEPSP). Conversely, the GABAB antagonist decreased these parameters along with decreased LTP induction. We also demonstrated that the co-administration of CB1 and GABAB antagonists had different effects on the PS amplitude and fEPSP slope. It is likely that GABAB receptor antagonists modulate cannabinoid outputs that cause a decrease in synaptic plastisity, while in the simultaneous consumption of two antagonists, CB1 antagonists can alter the release of GABA which in turn results in enhancement of LTP induction. These findings suggest that there are functional interactions between the CB1 and GABAB receptor in the hippocampus. PMID:26611204

  9. PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior

    Directory of Open Access Journals (Sweden)

    Ramsey Cara

    2008-07-01

    Full Text Available Abstract The laterocapsular division of the central nucleus of the amygdala (CeLC has emerged as an important site of pain-related plasticity and pain modulation. Glutamate and neuropeptide receptors in the CeLC contribute to synaptic and behavioral changes in the arthritis pain model, but the intracellular signaling pathways remain to be determined. This study addressed the role of PKA, PKC, and ERK in the CeLC. Adult male Sprague-Dawley rats were used in all experiments. Whole-cell patch-clamp recordings of CeLC neurons were made in brain slices from normal rats and from rats with a kaolin/carrageenan-induced monoarthritis in the knee (6 h postinduction. Membrane-permeable inhibitors of PKA (KT5720, 1 μM; cAMPS-Rp, 10 μM and ERK (U0126, 1 μM activation inhibited synaptic plasticity in slices from arthritic rats but had no effect on normal transmission in control slices. A PKC inhibitor (GF109203x, 1 μM and an inactive structural analogue of U0126 (U0124, 1 μM had no effect. The NMDA receptor-mediated synaptic component was inhibited by KT5720 or U0126; their combined application had additive effects. U0126 did not inhibit synaptic facilitation by forskolin-induced PKA-activation. Administration of KT5720 (100 μM, concentration in microdialysis probe or U0126 (100 μM into the CeLC, but not striatum (placement control, inhibited audible and ultrasonic vocalizations and spinal reflexes of arthritic rats but had no effect in normal animals. GF109203x (100 μM and U0124 (100 μM did not affect pain behavior. The data suggest that in the amygdala PKA and ERK, but not PKC, contribute to pain-related synaptic facilitation and behavior by increasing NMDA receptor function through independent signaling pathways.

  10. Time-dependent reversal of synaptic plasticity induced by physiological concentrations of oligomeric Aβ42: an early index of Alzheimer’s disease

    Science.gov (United States)

    Koppensteiner, Peter; Trinchese, Fabrizio; Fà, Mauro; Puzzo, Daniela; Gulisano, Walter; Yan, Shijun; Poussin, Arthur; Liu, Shumin; Orozco, Ian; Dale, Elena; Teich, Andrew F.; Palmeri, Agostino; Ninan, Ipe; Boehm, Stefan; Arancio, Ottavio

    2016-01-01

    The oligomeric amyloid-β (Aβ) peptide is thought to contribute to the subtle amnesic changes in Alzheimer’s disease (AD) by causing synaptic dysfunction. Here, we examined the time course of synaptic changes in mouse hippocampal neurons following exposure to Aβ42 at picomolar concentrations, mimicking its physiological levels in the brain. We found opposite effects of the peptide with short exposures in the range of minutes enhancing synaptic plasticity, and longer exposures lasting several hours reducing it. The plasticity reduction was concomitant with an increase in the basal frequency of spontaneous neurotransmitter release, a higher basal number of functional presynaptic release sites, and a redistribution of synaptic proteins including the vesicle-associated proteins synapsin I, synaptophysin, and the post-synaptic glutamate receptor I. These synaptic alterations were mediated by cytoskeletal changes involving actin polymerization and p38 mitogen-activated protein kinase. These in vitro findings were confirmed in vivo with short hippocampal infusions of picomolar Aβ enhancing contextual memory and prolonged infusions impairing it. Our findings provide a model for initiation of synaptic dysfunction whereby exposure to physiologic levels of Aβ for a prolonged period of time causes microstructural changes at the synapse which result in increased transmitter release, failure of synaptic plasticity, and memory loss. PMID:27581852

  11. LTS and FS inhibitory interneurons, short-term synaptic plasticity, and cortical circuit dynamics.

    Directory of Open Access Journals (Sweden)

    Itai Hayut

    2011-10-01

    Full Text Available Somatostatin-expressing, low threshold-spiking (LTS cells and fast-spiking (FS cells are two common subtypes of inhibitory neocortical interneuron. Excitatory synapses from regular-spiking (RS pyramidal neurons to LTS cells strongly facilitate when activated repetitively, whereas RS-to-FS synapses depress. This suggests that LTS neurons may be especially relevant at high rate regimes and protect cortical circuits against over-excitation and seizures. However, the inhibitory synapses from LTS cells usually depress, which may reduce their effectiveness at high rates. We ask: by which mechanisms and at what firing rates do LTS neurons control the activity of cortical circuits responding to thalamic input, and how is control by LTS neurons different from that of FS neurons? We study rate models of circuits that include RS cells and LTS and FS inhibitory cells with short-term synaptic plasticity. LTS neurons shift the RS firing-rate vs. current curve to the right at high rates and reduce its slope at low rates; the LTS effect is delayed and prolonged. FS neurons always shift the curve to the right and affect RS firing transiently. In an RS-LTS-FS network, FS neurons reach a quiescent state if they receive weak input, LTS neurons are quiescent if RS neurons receive weak input, and both FS and RS populations are active if they both receive large inputs. In general, FS neurons tend to follow the spiking of RS neurons much more closely than LTS neurons. A novel type of facilitation-induced slow oscillations is observed above the LTS firing threshold with a frequency determined by the time scale of recovery from facilitation. To conclude, contrary to earlier proposals, LTS neurons affect the transient and steady state responses of cortical circuits over a range of firing rates, not only during the high rate regime; LTS neurons protect against over-activation about as well as FS neurons.

  12. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot.

    Science.gov (United States)

    Grinke, Eduard; Tetzlaff, Christian; Wörgötter, Florentin; Manoonpong, Poramate

    2015-01-01

    Walking animals, like insects, with little neural computing can effectively perform complex behaviors. For example, they can walk around their environment, escape from corners/deadlocks, and avoid or climb over obstacles. While performing all these behaviors, they can also adapt their movements to deal with an unknown situation. As a consequence, they successfully navigate through their complex environment. The versatile and adaptive abilities are the result of an integration of several ingredients embedded in their sensorimotor loop. Biological studies reveal that the ingredients include neural dynamics, plasticity, sensory feedback, and biomechanics. Generating such versatile and adaptive behaviors for a many degrees-of-freedom (DOFs) walking robot is a challenging task. Thus, in this study, we present a bio-inspired approach to solve this task. Specifically, the approach combines neural mechanisms with plasticity, exteroceptive sensory feedback, and biomechanics. The neural mechanisms consist of adaptive neural sensory processing and modular neural locomotion control. The sensory processing is based on a small recurrent neural network consisting of two fully connected neurons. Online correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors) in the network to generate different turning angles with short-term memory for a walking robot. The turning information is transmitted as descending steering signals to the neural locomotion control which translates the signals into motor actions. As a result, the robot can walk around and adapt its turning angle for avoiding obstacles in different situations. The adaptation also enables the robot to effectively escape from sharp corners or deadlocks. Using backbone joint control embedded in the the locomotion control allows the robot to climb over small obstacles

  13. Evidence for high-fidelity timing-dependent synaptic plasticity of human motor cortex.

    Science.gov (United States)

    Cash, R F H; Mastaglia, F L; Thickbroom, G W

    2013-01-01

    A single transcranial magnetic stimulation (TMS) pulse typically evokes a short series of spikes in corticospinal neurons [known as indirect (I)-waves] which are thought to arise from transynaptic input. Delivering a second pulse at inter-pulse intervals (IPIs) corresponding to the timing of these I-waves leads to a facilitation of the response, and if stimulus pairs are delivered repeatedly, a persistent LTP-like increase in excitability can occur. This has been demonstrated at an IPI of 1.5 ms, which corresponds to the first I-wave interval, in an intervention referred to as ITMS (I-wave TMS), and it has been argued that this may have similarities with timing-dependent plasticity models. Consequently, we hypothesized that if the second stimulus is delivered so as not to coincide with I-wave timing, it should lead to LTD. We performed a crossover study in 10 subjects in which TMS doublets were timed to coincide (1.5-ms IPI, ITMS(1.5)) or not coincide (2-ms IPI, ITMS(2)) with I-wave firing. Single pulse motor-evoked potential (MEP) amplitude, resting motor threshold (RMT), and short-interval cortical inhibition (SICI) were measured from the first dorsal interosseous (FDI) muscle. After ITMS(1.5) corticomotor excitability was increased by ~60% for 15 min (P < 0.05) and returned to baseline by 20 min. Increasing the IPI by just 500 μs to 2 ms reversed the aftereffect, and MEP amplitude was significantly reduced (~35%, P < 0.05) for 15 min before returning to baseline. This reduction was not associated with an increase in SICI, suggesting a reduction in excitatory transmission rather than an increase in inhibitory efficacy. RMT also remained unchanged, suggesting that these changes were not due to changes in membrane excitability. Amplitude-matching ITMS(2) did not modulate excitability. The results are consistent with timing-dependent synaptic LTP/D-like effects and suggest that there are plasticity mechanisms operating in the human motor cortex with a temporal

  14. The Plastic Glial-Synaptic Dynamics within the Neuropil: A Self-Organizing System Composed of Polyelectrolytes in Phase Transition

    Directory of Open Access Journals (Sweden)

    Vera Maura Fernandes de Lima

    2016-01-01

    Full Text Available Several explanations have been proposed to account for the mechanisms of neuroglial interactions involved in neural plasticity. We review experimental results addressing plastic nonlinear interactions between glial membranes and synaptic terminals. These results indicate the necessity of elaborating on a model based on the dynamics of hydroionic waves within the neuropil. These waves have been detected in a small scale experimental model of the central nervous system, the in vitro retina. We suggest that the brain, as the heart and kidney, is a system for which the state of water is functional. The use of nonlinear thermodynamics supports experiments at convenient biological spatiotemporal scales, while an understanding of the properties of ions and their interactions with water requires explanations based on quantum theories. In our approach, neural plasticity is seen as part of a larger process that encompasses higher brain functions; in this regard, hydroionic waves within the neuropil are considered to carry both physiological and cognitive functions.

  15. The Plastic Glial-Synaptic Dynamics within the Neuropil: A Self-Organizing System Composed of Polyelectrolytes in Phase Transition

    Science.gov (United States)

    Fernandes de Lima, Vera Maura; Pereira, Alfredo

    2016-01-01

    Several explanations have been proposed to account for the mechanisms of neuroglial interactions involved in neural plasticity. We review experimental results addressing plastic nonlinear interactions between glial membranes and synaptic terminals. These results indicate the necessity of elaborating on a model based on the dynamics of hydroionic waves within the neuropil. These waves have been detected in a small scale experimental model of the central nervous system, the in vitro retina. We suggest that the brain, as the heart and kidney, is a system for which the state of water is functional. The use of nonlinear thermodynamics supports experiments at convenient biological spatiotemporal scales, while an understanding of the properties of ions and their interactions with water requires explanations based on quantum theories. In our approach, neural plasticity is seen as part of a larger process that encompasses higher brain functions; in this regard, hydroionic waves within the neuropil are considered to carry both physiological and cognitive functions. PMID:26949548

  16. Persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis

    Directory of Open Access Journals (Sweden)

    Valentina eWiescholleck

    2013-03-01

    Full Text Available Irreversible N-methyl-D-aspartate receptor (NMDAR antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments.The ability to express long-term potentiation (LTP at the perforant pathway – dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3 and 4 weeks after a single -treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue.Taken together, these data support that acute treatment with an irreversible NMDAR antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.

  17. Age-related deficits in synaptic plasticity rescued by activating PKA or PKC in sensory neurons of Aplysia californica

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    Andrew T Kempsell

    2015-09-01

    Full Text Available Brain aging is associated with declines in synaptic function that contribute to memory loss, including reduced postsynaptic response to neurotransmitters and decreased neuronal excitability. To understand how aging affects memory in a simple neural circuit, we studied neuronal proxies of memory for sensitization in mature versus advanced age Aplysia. Glutamate- (L-Glu- evoked excitatory currents were facilitated by the neuromodulator serotonin (5-HT in sensory neurons (SN isolated from mature but not aged animals. Activation of PKA and PKC signaling rescued facilitation of L-Glu currents in aged SN. Similarly, PKA and PKC activators restored increased excitability in aged tail SN. These results suggest that altered synaptic plasticity during aging involves defects in second messenger systems

  18. Levetiracetam attenuates hippocampal expression of synaptic plasticity-related immediate early and late response genes in amygdala-kindled rats

    Directory of Open Access Journals (Sweden)

    Watson William P

    2010-01-01

    Full Text Available Abstract Background The amygdala-kindled rat is a model for human temporal lobe epilepsy and activity-dependent synaptic plasticity. Hippocampal RNA isolated from amygdala-kindled rats at different kindling stages was analyzed to identify kindling-induced genes. Furthermore, effects of the anti-epileptic drug levetiracetam on kindling-induced gene expression were examined. Results Cyclooxygenase-2 (Cox-2, Protocadherin-8 (Pcdh8 and TGF-beta-inducible early response gene-1 (TIEG1 were identified and verified as differentially expressed transcripts in the hippocampus of kindled rats by in situ hybridization and quantitative RT-PCR. In addition, we identified a panel of 16 additional transcripts which included Arc, Egr3/Pilot, Homer1a, Ania-3, MMP9, Narp, c-fos, NGF, BDNF, NT-3, Synaptopodin, Pim1 kinase, TNF-α, RGS2, Egr2/krox-20 and β-A activin that were differentially expressed in the hippocampus of amygdala-kindled rats. The list consists of many synaptic plasticity-related immediate early genes (IEGs as well as some late response genes encoding transcription factors, neurotrophic factors and proteins that are known to regulate synaptic remodelling. In the hippocampus, induction of IEG expression was dependent on the afterdischarge (AD duration. Levetiracetam, 40 mg/kg, suppressed the development of kindling measured as severity of seizures and AD duration. In addition, single animal profiling also showed that levetiracetam attenuated the observed kindling-induced IEG expression; an effect that paralleled the anti-epileptic effect of the drug on AD duration. Conclusions The present study provides mRNA expression data that suggest that levetiracetam attenuates expression of genes known to regulate synaptic remodelling. In the kindled rat, levetiracetam does so by shortening the AD duration thereby reducing the seizure-induced changes in mRNA expression in the hippocampus.

  19. Levetiracetam attenuates hippocampal expression of synaptic plasticity-related immediate early and late response genes in amygdala-kindled rats

    Science.gov (United States)

    2010-01-01

    Background The amygdala-kindled rat is a model for human temporal lobe epilepsy and activity-dependent synaptic plasticity. Hippocampal RNA isolated from amygdala-kindled rats at different kindling stages was analyzed to identify kindling-induced genes. Furthermore, effects of the anti-epileptic drug levetiracetam on kindling-induced gene expression were examined. Results Cyclooxygenase-2 (Cox-2), Protocadherin-8 (Pcdh8) and TGF-beta-inducible early response gene-1 (TIEG1) were identified and verified as differentially expressed transcripts in the hippocampus of kindled rats by in situ hybridization and quantitative RT-PCR. In addition, we identified a panel of 16 additional transcripts which included Arc, Egr3/Pilot, Homer1a, Ania-3, MMP9, Narp, c-fos, NGF, BDNF, NT-3, Synaptopodin, Pim1 kinase, TNF-α, RGS2, Egr2/krox-20 and β-A activin that were differentially expressed in the hippocampus of amygdala-kindled rats. The list consists of many synaptic plasticity-related immediate early genes (IEGs) as well as some late response genes encoding transcription factors, neurotrophic factors and proteins that are known to regulate synaptic remodelling. In the hippocampus, induction of IEG expression was dependent on the afterdischarge (AD) duration. Levetiracetam, 40 mg/kg, suppressed the development of kindling measured as severity of seizures and AD duration. In addition, single animal profiling also showed that levetiracetam attenuated the observed kindling-induced IEG expression; an effect that paralleled the anti-epileptic effect of the drug on AD duration. Conclusions The present study provides mRNA expression data that suggest that levetiracetam attenuates expression of genes known to regulate synaptic remodelling. In the kindled rat, levetiracetam does so by shortening the AD duration thereby reducing the seizure-induced changes in mRNA expression in the hippocampus. PMID:20105316

  20. Alterations in synaptic plasticity coincide with deficits in spatial working memory in presymptomatic 3xTg-AD mice.

    Science.gov (United States)

    Clark, Jason K; Furgerson, Matthew; Crystal, Jonathon D; Fechheimer, Marcus; Furukawa, Ruth; Wagner, John J

    2015-11-01

    Alzheimer's disease is a neurodegenerative condition believed to be initiated by production of amyloid-beta peptide, which leads to synaptic dysfunction and progressive memory loss. Using a mouse model of Alzheimer's disease (3xTg-AD), an 8-arm radial maze was employed to assess spatial working memory. Unexpectedly, the younger (3month old) 3xTg-AD mice were as impaired in the spatial working memory task as the older (8month old) 3xTg-AD mice when compared with age-matched NonTg control animals. Field potential recordings from the CA1 region of slices prepared from the ventral hippocampus were obtained to assess synaptic transmission and capability for synaptic plasticity. At 3months of age, the NMDA receptor-dependent component of LTP was reduced in 3xTg-AD mice. However, the magnitude of the non-NMDA receptor-dependent component of LTP was concomitantly increased, resulting in a similar amount of total LTP in 3xTg-AD and NonTg mice. At 8months of age, the NMDA receptor-dependent LTP was again reduced in 3xTg-AD mice, but now the non-NMDA receptor-dependent component was decreased as well, resulting in a significantly reduced total amount of LTP in 3xTg-AD compared with NonTg mice. Both 3 and 8month old 3xTg-AD mice exhibited reductions in paired-pulse facilitation and NMDA receptor-dependent LTP that coincided with the deficit in spatial working memory. The early presence of this cognitive impairment and the associated alterations in synaptic plasticity demonstrate that the onset of some behavioral and neurophysiological consequences can occur before the detectable presence of plaques and tangles in the 3xTg-AD mouse model of Alzheimer's disease.

  1. 突触可塑性分子机制的相关研究%Molecular Mechanisms of Synaptic Plasticity Related Research

    Institute of Scientific and Technical Information of China (English)

    张永杰

    2012-01-01

    In recent years,researchers have paid close attention to the role of synaptic plasticity in learning and memory. Synaptic is a key part of neural information transmission, and synaptic plasticity is considered as synaptic changes, the new synaptic formation and the establishment of transmission performance. Synaptic plasticity is the molecular basis of learning and memory, which mediates the transmission of nerve excitability, and has a major influence on synaptic plasticity of neurons establishment, therefore is closely related to learning and memory. Here is to make a review on the molecular mechanisms of synaptic plasticity in learning and memory.%近年来,突触可塑性在学习记忆中所产生的作用一直是人们关注的焦点.突触是神经信息传递的关键部位,突触可塑性被认为是突触形态的改变、新的突触的形成及传递性能的建立,突触可塑性是学习与记忆的细胞分子学基础,其介导了神经兴奋性的传导,对神经元突触可塑性和神经构筑产生了重要影响,因而与学习记忆关系密切.现就突触可塑性分子机制对学习记忆的影响进行综述.

  2. Plasticity of GABA transporters: an unconventional route to shape inhibitory synaptic transmission

    OpenAIRE

    Annalisa eScimemi

    2014-01-01

    The brain relies on GABAergic neurons to control the ongoing activity of neuronal networks. GABAergic neurons control the firing pattern of excitatory cells, the temporal structure of membrane potential oscillations and the time window for integration of synaptic inputs. These actions require a fine control of the timing of GABA receptor activation which, in turn, depends on the precise timing of GABA release from pre-synaptic terminals and GABA clearance from the extracellular space. Extrace...

  3. Late onset deficits in synaptic plasticity in the valproic acid rat model of autism

    Directory of Open Access Journals (Sweden)

    Henry Giles Stratten Martin

    2014-01-01

    Full Text Available Valproic acid (VPA is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC physiology and synaptic connectivity. Specifically, principal neurons show decreased excitability but increased local connectivity, coupled with an increase in long-term potentiation (LTP due to an up-regulation of NMDA receptor (NMDAR expression. However recent evidence suggests compensatory homeostatic mechanisms lead to normalization of synaptic NMDA receptors during later postnatal development. Here we have extended study of mPFC synaptic physiology into adulthood to better understand the longitudinal consequences of early developmental abnormalities in VPA exposed rats. Surprisingly in contrast to early postnatal life and adolescence, we find that adult VPA exposed rats show reduced synaptic function. Both NMDAR mediated currents and LTP are lower in adult VPA rats, although spontaneous activity and endocannabinoid dependent long-term depression are normal. We conclude that rather than correcting, synaptic abnormalities persist into adulthood in VPA exposed rats, although a quite different synaptic phenotype is present. This switch from hyper to hypo function in mPFC may be linked to some of the neurodevelopmental defects found in prenatal VPA exposure and autism spectrum disorders in general.

  4. Is a 4-bit synaptic weight resolution enough? - constraints on enabling spike-timing dependent plasticity in neuromorphic hardware.

    Science.gov (United States)

    Pfeil, Thomas; Potjans, Tobias C; Schrader, Sven; Potjans, Wiebke; Schemmel, Johannes; Diesmann, Markus; Meier, Karlheinz

    2012-01-01

    Large-scale neuromorphic hardware systems typically bear the trade-off between detail level and required chip resources. Especially when implementing spike-timing dependent plasticity, reduction in resources leads to limitations as compared to floating point precision. By design, a natural modification that saves resources would be reducing synaptic weight resolution. In this study, we give an estimate for the impact of synaptic weight discretization on different levels, ranging from random walks of individual weights to computer simulations of spiking neural networks. The FACETS wafer-scale hardware system offers a 4-bit resolution of synaptic weights, which is shown to be sufficient within the scope of our network benchmark. Our findings indicate that increasing the resolution may not even be useful in light of further restrictions of customized mixed-signal synapses. In addition, variations due to production imperfections are investigated and shown to be uncritical in the context of the presented study. Our results represent a general framework for setting up and configuring hardware-constrained synapses. We suggest how weight discretization could be considered for other backends dedicated to large-scale simulations. Thus, our proposition of a good hardware verification practice may rise synergy effects between hardware developers and neuroscientists.

  5. The Impact of Stimulation Induced Short Term Synaptic Plasticity on Firing Patterns in the Globus Pallidus of the Rat

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    Jenia eBugaysen

    2011-03-01

    Full Text Available Electrical stimulation in the globus pallidus (GP leads to complex modulations of neuronal activity in the stimulated nucleus. Multiple in-vivo studies have demonstrated the modulation of both firing rates and patterns during and immediately following the GP stimulation. Previous in-vitro studies, together with computational studies, have suggested the involvement of short-term synaptic plasticity (STP during the stimulation. The aim of the current study was to explore in-vitro the effects of STP on neuronal activity of GP neurons during local repetitive stimulation. We recorded synaptic potentials and assessed the modulations of spontaneous firing in a postsynaptic neuron in acute brain slices via a whole-cell pipette. Low-frequency repetitive stimulation locked the firing of the neuron to the stimulus. However, high-frequency repetitive stimulation in the GP generated a biphasic modulation of the firing frequency consisting of inhibitory and excitatory phases. Using blockers of synaptic transmission, we show that GABAergic synapses mediated the inhibitory and glutamatergic synapses the excitatory part of the response. Furthermore, we report that at high stimulation frequencies both types of synapses undergo short-term depression leading to a time dependent modulation of the neuronal firing. These findings indicate that STP modulates the dynamic responses of pallidal activity during electrical stimulation, and may contribute to a better understanding of the mechanism underlying deep brain stimulation (DBS like protocols.

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

    Science.gov (United States)

    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…

  7. The role of additive neurogenesis and synaptic plasticity in a hippocampal memory model with grid-cell like input.

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    Peter A Appleby

    Full Text Available Recently, we presented a study of adult neurogenesis in a simplified hippocampal memory model. The network was required to encode and decode memory patterns despite changing input statistics. We showed that additive neurogenesis was a more effective adaptation strategy compared to neuronal turnover and conventional synaptic plasticity as it allowed the network to respond to changes in the input statistics while preserving representations of earlier environments. Here we extend our model to include realistic, spatially driven input firing patterns in the form of grid cells in the entorhinal cortex. We compare network performance across a sequence of spatial environments using three distinct adaptation strategies: conventional synaptic plasticity, where the network is of fixed size but the connectivity is plastic; neuronal turnover, where the network is of fixed size but units in the network may die and be replaced; and additive neurogenesis, where the network starts out with fewer initial units but grows over time. We confirm that additive neurogenesis is a superior adaptation strategy when using realistic, spatially structured input patterns. We then show that a more biologically plausible neurogenesis rule that incorporates cell death and enhanced plasticity of new granule cells has an overall performance significantly better than any one of the three individual strategies operating alone. This adaptation rule can be tailored to maximise performance of the network when operating as either a short- or long-term memory store. We also examine the time course of adult neurogenesis over the lifetime of an animal raised under different hypothetical rearing conditions. These growth profiles have several distinct features that form a theoretical prediction that could be tested experimentally. Finally, we show that place cells can emerge and refine in a realistic manner in our model as a direct result of the sparsification performed by the dentate gyrus

  8. Spatiotemporal discrimination in neural networks with short-term synaptic plasticity

    Science.gov (United States)

    Shlaer, Benjamin; Miller, Paul

    2015-03-01

    Cells in recurrently connected neural networks exhibit bistability, which allows for stimulus information to persist in a circuit even after stimulus offset, i.e. short-term memory. However, such a system does not have enough hysteresis to encode temporal information about the stimuli. The biophysically described phenomenon of synaptic depression decreases synaptic transmission strengths due to increased presynaptic activity. This short-term reduction in synaptic strengths can destabilize attractor states in excitatory recurrent neural networks, causing the network to move along stimulus dependent dynamical trajectories. Such a network can successfully separate amplitudes and durations of stimuli from the number of successive stimuli. Stimulus number, duration and intensity encoding in randomly connected attractor networks with synaptic depression. Front. Comput. Neurosci. 7:59., and so provides a strong candidate network for the encoding of spatiotemporal information. Here we explicitly demonstrate the capability of a recurrent neural network with short-term synaptic depression to discriminate between the temporal sequences in which spatial stimuli are presented.

  9. Synaptic plasticity in GNGA3-/- mice: Cone bipolar cells react up0onthe missing cone input and form ectopic synapses with rods

    OpenAIRE

    Humphries, Peter

    2006-01-01

    PUBLISHED In the mammalian retina, rods and cones connect to distinct sets of bipolar cells. Rods are presynaptic to a single type of rod bipolar cell, whereas cones connect to different types of cone bipolar cells. Synaptic rewiring between cone photoreceptor terminals and rod bipolar cell dendrites has been described as a general result of photoreceptor degeneration. To investigate whether cone bipolar cells also show synaptic plasticity in the absence of cone input, we studied the conne...

  10. Schisandra N-butanol extract improves synaptic morphology and plasticity in ovarectomized mice

    Institute of Scientific and Technical Information of China (English)

    Meiyan Yang; Zhaolin Cai; Peng Xiao; Chuhua Li

    2012-01-01

    Preliminary work by our research team revealed that Schisandra, a renowned traditional Chinese medicine, causes learning and memory improvements in ovariectomized mice. This activity was attributed to active ingredients extracted with N-butyl alcohol, named Schisandra N-butanol extract. In this study, ovariectomized mice were pretreated with Schisandra N-butanol extract given by intragastric administration. This treatment led to the enhancement of learning, and an increase in hippocampal CA1 synaptic, surface and postsynaptic density. A decrease in the average size of the synaptic active zone was also observed. These experimental findings showing that Schisandra N-butanol extract improved synaptic morphology indicate an underlying mechanism by which the ability of learning is enhanced in ovariectomized mice.

  11. Roles of MicroRNA in synaptic plasticity%MicroRNA在突触可塑性中的作用

    Institute of Scientific and Technical Information of China (English)

    胡雪玲; 孙丽华

    2014-01-01

    microRNAs (miRNA) are small endogenous non-coding RNAs of approximately 22 nucleotides that play a crucial role in the post-transcriptional gene regulation. miRNAs are enriched in the brain, where they can contribute significantly to the development, survival of neurons, meanwhile they might be important mediators of neural functions, such as synaptic plasticity. This review discusses the regulation of miRNAs in synaptic plasticity.%microRNA(miRNA)是一种内源性的,长度<为22 nt的非编码小分子RNA,对基因的转录后调控具有重要作用。miRNAs在脑中大量表达,对神经元的生长发育起关键作用,同时miRNAs还参与神经功能的实施,如突触可塑性。本文将重点讨论miRNAs对神经突触可塑性的调节作用。

  12. p140Cap regulates memory and synaptic plasticity through Src-mediated and citron-N-mediated actin reorganization.

    Science.gov (United States)

    Repetto, Daniele; Camera, Paola; Melani, Riccardo; Morello, Noemi; Russo, Isabella; Calcagno, Eleonora; Tomasoni, Romana; Bianchi, Federico; Berto, Gaia; Giustetto, Maurizio; Berardi, Nicoletta; Pizzorusso, Tommaso; Matteoli, Michela; Di Stefano, Paola; Missler, Markus; Turco, Emilia; Di Cunto, Ferdinando; Defilippi, Paola

    2014-01-22

    A major challenge in the neuroscience field is the identification of molecules and pathways that control synaptic plasticity and memory. Dendritic spines play a pivotal role in these processes, as the major sites of excitatory synapses in neuronal communication. Previous studies have shown that the scaffold protein p140Cap localizes into dendritic spines and that its knockdown negatively modulates spine shape in culture. However, so far, there is no information on its in vivo relevance. By using a knock-out mouse model, we here demonstrate that p140Cap is a key element for both learning and synaptic plasticity. Indeed, p140Cap(-/-) mice are impaired in object recognition test, as well as in LTP and in LTD measurements. The in vivo effects of p140Cap loss are presumably attenuated by noncell-autonomous events, since primary neurons obtained from p140Cap(-/-) mice show a strong reduction in number of mushroom spines and abnormal organization of synapse-associated F-actin. These phenotypes are most likely caused by a local reduction of the inhibitory control of RhoA and of cortactin toward the actin-depolymerizing factor cofilin. These events can be controlled by p140Cap through its capability to directly inhibit the activation of Src kinase and by its binding to the scaffold protein Citron-N. Altogether, our results provide new insight into how protein associated with dynamic microtubules may regulate spine actin organization through interaction with postsynaptic density components. PMID:24453341

  13. Neto1 is a novel CUB-domain NMDA receptor-interacting protein required for synaptic plasticity and learning.

    Directory of Open Access Journals (Sweden)

    David Ng

    2009-02-01

    Full Text Available The N-methyl-D-aspartate receptor (NMDAR, a major excitatory ligand-gated ion channel in the central nervous system (CNS, is a principal mediator of synaptic plasticity. Here we report that neuropilin tolloid-like 1 (Neto1, a complement C1r/C1s, Uegf, Bmp1 (CUB domain-containing transmembrane protein, is a novel component of the NMDAR complex critical for maintaining the abundance of NR2A-containing NMDARs in the postsynaptic density. Neto1-null mice have depressed long-term potentiation (LTP at Schaffer collateral-CA1 synapses, with the subunit dependency of LTP induction switching from the normal predominance of NR2A- to NR2B-NMDARs. NMDAR-dependent spatial learning and memory is depressed in Neto1-null mice, indicating that Neto1 regulates NMDA receptor-dependent synaptic plasticity and cognition. Remarkably, we also found that the deficits in LTP, learning, and memory in Neto1-null mice were rescued by the ampakine CX546 at doses without effect in wild-type. Together, our results establish the principle that auxiliary proteins are required for the normal abundance of NMDAR subunits at synapses, and demonstrate that an inherited learning defect can be rescued pharmacologically, a finding with therapeutic implications for humans.

  14. Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

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    Alexander David Bird

    2014-01-01

    Full Text Available Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modifed during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony setby the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture.

  15. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity.

  16. Chronic methamphetamine treatment reduces the expression of synaptic plasticity genes and changes their DNA methylation status in the mouse brain.

    Science.gov (United States)

    Cheng, Min-Chih; Hsu, Shih-Hsin; Chen, Chia-Hsiang

    2015-12-10

    Methamphetamine (METH) is a highly addictive psychostimulant that may cause long-lasting synaptic dysfunction and abnormal gene expression. We aimed to explore the differential expression of synaptic plasticity genes in chronic METH-treated mouse brain. We used the RT(2) Profiler PCR Array and the real-time quantitative PCR to characterize differentially expressed synaptic plasticity genes in the frontal cortex and the hippocampus of chronic METH-treated mice compared with normal saline-treated mice. We further used pyrosequencing to assess DNA methylation changes in the CpG region of the five immediate early genes (IEGs) in chronic METH-treated mouse brain. We detected six downregulated genes in the frontal cortex and the hippocampus of chronic METH-treated mice, including five IEGs (Arc, Egr2, Fos, Klf10, and Nr4a1) and one neuronal receptor gene (Grm1), compared with normal saline-treated group, but only four genes (Arc, Egr2, Fos, and Nr4a1) were confirmed to be different. Furthermore, we found several CpG sites of the Arc and the Fos that had significant changes in DNA methylation status in the frontal cortex of chronic METH-treated mice, while the klf10 and the Nr4a1 that had significant changes in the hippocampus. Our results show that chronic administration of METH may lead to significant downregulation of the IEGs expression in both the frontal cortex and the hippocampus, which may partly account for the molecular mechanism of the action of METH. Furthermore, the changes in DNA methylation status of the IEGs in the brain indicate that an epigenetic mechanism-dependent transcriptional regulation may contribute to METH addiction, which warrants additional study. PMID:26496011

  17. Exercise, Alzheimer's Disease and Synaptic Plasticity (review)%运动、阿尔茨海默病与突触可塑性

    Institute of Scientific and Technical Information of China (English)

    刘慧莉; 赵刚

    2012-01-01

    Exercise can improve cognitive performance in Alzheimer's disease (AD), which may involve in synaptic plasticity. This paper reviewed the benefit of exercise on AD, the synaptic plasticity in AD, and the effects of exercise on synaptic plasticity.%运动能够减缓阿尔茨海默病(AD)的发病和进展,突触可塑性可能是AD学习和记忆功能障碍的神经生物学基础,也是运动防治AD的细胞机制.本文就运动对AD的防治作用、AD突触可塑性的改变及运动对突触可塑性的影响进行综述.

  18. Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides

    Science.gov (United States)

    Wang, Dongmei; Mitchell, Ellen S.

    2016-01-01

    Brain glucose hypometabolism is a common feature of Alzheimer’s disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612) phosphorylation and decreased S6K phosphorylation (240/244) but only MCT10 increased Akt phosphorylation (473). MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1) were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels. PMID:27517611

  19. Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides.

    Science.gov (United States)

    Wang, Dongmei; Mitchell, Ellen S

    2016-01-01

    Brain glucose hypometabolism is a common feature of Alzheimer's disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612) phosphorylation and decreased S6K phosphorylation (240/244) but only MCT10 increased Akt phosphorylation (473). MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1) were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels. PMID:27517611

  20. Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice.

    Directory of Open Access Journals (Sweden)

    Rebecca C Klein

    Full Text Available The human apolipoprotein ε4 allele (APOE4 has been implicated as one of the strongest genetic risk factors associated with Alzheimer's disease (AD and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD.

  1. Experimental demonstration of a second-order memristor and its ability to biorealistically implement synaptic plasticity.

    Science.gov (United States)

    Kim, Sungho; Du, Chao; Sheridan, Patrick; Ma, Wen; Choi, ShinHyun; Lu, Wei D

    2015-03-11

    Memristors have been extensively studied for data storage and low-power computation applications. In this study, we show that memristors offer more than simple resistance change. Specifically, the dynamic evolutions of internal state variables allow an oxide-based memristor to exhibit Ca(2+)-like dynamics that natively encode timing information and regulate synaptic weights. Such a device can be modeled as a second-order memristor and allow the implementation of critical synaptic functions realistically using simple spike forms based solely on spike activity. PMID:25710872

  2. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Harsh Sancheti

    Full Text Available Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD that shows progression of pathology as a function of age; two age groups: 6 months (young and 12 months (old were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O and long term potentiation (LTP (measured by electrophysiology. Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  3. Synaptic plasticity in a recurrent neural network for versatile and adaptive behaviors of a walking robot

    DEFF Research Database (Denmark)

    Grinke, Eduard; Tetzlaff, Christian; Wörgötter, Florentin;

    2015-01-01

    correlation-based learning with synaptic scaling is applied to adequately change the connections of the network. By doing so, we can effectively exploit neural dynamics (i.e., hysteresis effects and single attractors) in the network to generate different turning angles with short-term memory for a walking...

  4. Experience with the "good" limb induces aberrant synaptic plasticity in the perilesion cortex after stroke.

    Science.gov (United States)

    Kim, Soo Young; Allred, Rachel P; Adkins, DeAnna L; Tennant, Kelly A; Donlan, Nicole A; Kleim, Jeffrey A; Jones, Theresa A

    2015-06-01

    Following unilateral stroke, the contralateral (paretic) body side is often severely impaired, and individuals naturally learn to rely more on the nonparetic body side, which involves learning new skills with it. Such compensatory hyper-reliance on the "good" body side, however, can limit functional improvements of the paretic side. In rats, motor skill training with the nonparetic forelimb (NPT) following a unilateral infarct lessens the efficacy of rehabilitative training, and reduces neuronal activation in perilesion motor cortex. However, the underlying mechanisms remain unclear. In the present study, we investigated how forelimb movement representations and synaptic restructuring in perilesion motor cortex respond to NPT and their relationship with behavioral outcomes. Forelimb representations were diminished as a result of NPT, as revealed with intracortical microstimulation mapping. Using transmission electron microscopy and stereological analyses, we found that densities of axodendritic synapses, especially axo-spinous synapses, as well as multiple synaptic boutons were increased in the perilesion cortex by NPT. The synaptic density was negatively correlated with the functional outcome of the paretic limb, as revealed in reaching performance. Furthermore, in animals with NPT, there was dissociation between astrocytic morphological features and axo-spinous synaptic density in perilesion motor cortex, compared with controls. These findings demonstrate that skill learning with the nonparetic limb following unilateral brain damage results in aberrant synaptogenesis, potentially of transcallosal projections, and this seems to hamper the functionality of the perilesion motor cortex and the paretic forelimb. PMID:26041926

  5. Closed-loop Robots Driven by Short-Term Synaptic Plasticity: Emergent Explorative vs. Limit-Cycle Locomotion

    Science.gov (United States)

    Martin, Laura; Sándor, Bulcsú; Gros, Claudius

    2016-01-01

    We examine the hypothesis, that short-term synaptic plasticity (STSP) may generate self-organized motor patterns. We simulated sphere-shaped autonomous robots, within the LPZRobots simulation package, containing three weights moving along orthogonal internal rods. The position of a weight is controlled by a single neuron receiving excitatory input from the sensor, measuring its actual position, and inhibitory inputs from the other two neurons. The inhibitory connections are transiently plastic, following physiologically inspired STSP-rules. We find that a wide palette of motion patterns are generated through the interaction of STSP, robot, and environment (closed-loop configuration), including various forward meandering and circular motions, together with chaotic trajectories. The observed locomotion is robust with respect to additional interactions with obstacles. In the chaotic phase the robot is seemingly engaged in actively exploring its environment. We believe that our results constitute a concept of proof that transient synaptic plasticity, as described by STSP, may potentially be important for the generation of motor commands and for the emergence of complex locomotion patterns, adapting seamlessly also to unexpected environmental feedback. We observe spontaneous and collision induced mode switchings, finding in addition, that locomotion may follow transiently limit cycles which are otherwise unstable. Regular locomotion corresponds to stable limit cycles in the sensorimotor loop, which may be characterized in turn by arbitrary angles of propagation. This degeneracy is, in our analysis, one of the drivings for the chaotic wandering observed for selected parameter settings, which is induced by the smooth diffusion of the angle of propagation. PMID:27803661

  6. Late onset deficits in synaptic plasticity in the valproic acid rat model of autism

    OpenAIRE

    Henry Giles Stratten Martin; Olivier eManzoni

    2014-01-01

    Valproic acid (VPA) is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC) physiology and synaptic connectivity...

  7. Activity-Dependent Synaptic Plasticity of a Chalcogenide Electronic Synapse for Neuromorphic Systems

    OpenAIRE

    Yi Li; Yingpeng Zhong; Jinjian Zhang; Lei Xu; Qing Wang; Huajun Sun; Hao Tong; Xiaoming Cheng; Xiangshui Miao

    2014-01-01

    Nanoscale inorganic electronic synapses or synaptic devices, which are capable of emulating the functions of biological synapses of brain neuronal systems, are regarded as the basic building blocks for beyond-Von Neumann computing architecture, combining information storage and processing. Here, we demonstrate a Ag/AgInSbTe/Ag structure for chalcogenide memristor-based electronic synapses. The memristive characteristics with reproducible gradual resistance tuning are utilised to mimic the act...

  8. Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals

    Science.gov (United States)

    Errico, F; Nisticò, R; Di Giorgio, A; Squillace, M; Vitucci, D; Galbusera, A; Piccinin, S; Mango, D; Fazio, L; Middei, S; Trizio, S; Mercuri, N B; Teule, M A; Centonze, D; Gozzi, A; Blasi, G; Bertolino, A; Usiello, A

    2014-01-01

    D-aspartate (D-Asp) is an atypical amino acid, which is especially abundant in the developing mammalian brain, and can bind to and activate N-methyl-D-Aspartate receptors (NMDARs). In line with its pharmacological features, we find that mice chronically treated with D-Asp show enhanced NMDAR-mediated miniature excitatory postsynaptic currents and basal cerebral blood volume in fronto-hippocampal areas. In addition, we show that both chronic administration of D-Asp and deletion of the gene coding for the catabolic enzyme D-aspartate oxidase (DDO) trigger plastic modifications of neuronal cytoarchitecture in the prefrontal cortex and CA1 subfield of the hippocampus and promote a cytochalasin D-sensitive form of synaptic plasticity in adult mouse brains. To translate these findings in humans and consistent with the experiments using Ddo gene targeting in animals, we performed a hierarchical stepwise translational genetic approach. Specifically, we investigated the association of variation in the gene coding for DDO with complex human prefrontal phenotypes. We demonstrate that genetic variation predicting reduced expression of DDO in postmortem human prefrontal cortex is mapped on greater prefrontal gray matter and activity during working memory as measured with MRI. In conclusion our results identify novel NMDAR-dependent effects of D-Asp on plasticity and physiology in rodents, which also map to prefrontal phenotypes in humans. PMID:25072322

  9. Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals.

    Science.gov (United States)

    Errico, F; Nisticò, R; Di Giorgio, A; Squillace, M; Vitucci, D; Galbusera, A; Piccinin, S; Mango, D; Fazio, L; Middei, S; Trizio, S; Mercuri, N B; Teule, M A; Centonze, D; Gozzi, A; Blasi, G; Bertolino, A; Usiello, A

    2014-01-01

    D-aspartate (D-Asp) is an atypical amino acid, which is especially abundant in the developing mammalian brain, and can bind to and activate N-methyl-D-Aspartate receptors (NMDARs). In line with its pharmacological features, we find that mice chronically treated with D-Asp show enhanced NMDAR-mediated miniature excitatory postsynaptic currents and basal cerebral blood volume in fronto-hippocampal areas. In addition, we show that both chronic administration of D-Asp and deletion of the gene coding for the catabolic enzyme D-aspartate oxidase (DDO) trigger plastic modifications of neuronal cytoarchitecture in the prefrontal cortex and CA1 subfield of the hippocampus and promote a cytochalasin D-sensitive form of synaptic plasticity in adult mouse brains. To translate these findings in humans and consistent with the experiments using Ddo gene targeting in animals, we performed a hierarchical stepwise translational genetic approach. Specifically, we investigated the association of variation in the gene coding for DDO with complex human prefrontal phenotypes. We demonstrate that genetic variation predicting reduced expression of DDO in postmortem human prefrontal cortex is mapped on greater prefrontal gray matter and activity during working memory as measured with MRI. In conclusion our results identify novel NMDAR-dependent effects of D-Asp on plasticity and physiology in rodents, which also map to prefrontal phenotypes in humans.

  10. In Vitro Studies of Neuronal Networks and Synaptic Plasticity in Invertebrates and in Mammals Using Multielectrode Arrays

    Directory of Open Access Journals (Sweden)

    Paolo Massobrio

    2015-01-01

    Full Text Available Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments.

  11. In vitro studies of neuronal networks and synaptic plasticity in invertebrates and in mammals using multielectrode arrays.

    Science.gov (United States)

    Massobrio, Paolo; Tessadori, Jacopo; Chiappalone, Michela; Ghirardi, Mirella

    2015-01-01

    Brain functions are strictly dependent on neural connections formed during development and modified during life. The cellular and molecular mechanisms underlying synaptogenesis and plastic changes involved in learning and memory have been analyzed in detail in simple animals such as invertebrates and in circuits of mammalian brains mainly by intracellular recordings of neuronal activity. In the last decades, the evolution of techniques such as microelectrode arrays (MEAs) that allow simultaneous, long-lasting, noninvasive, extracellular recordings from a large number of neurons has proven very useful to study long-term processes in neuronal networks in vivo and in vitro. In this work, we start off by briefly reviewing the microelectrode array technology and the optimization of the coupling between neurons and microtransducers to detect subthreshold synaptic signals. Then, we report MEA studies of circuit formation and activity in invertebrate models such as Lymnaea, Aplysia, and Helix. In the following sections, we analyze plasticity and connectivity in cultures of mammalian dissociated neurons, focusing on spontaneous activity and electrical stimulation. We conclude by discussing plasticity in closed-loop experiments.

  12. Synaptically Released Matrix Metalloproteinase Activity in Control of Structural Plasticity and the Cell Surface Distribution of GluA1-AMPA Receptors

    OpenAIRE

    Zsuzsanna Szepesi; Eric Hosy; Blazej Ruszczycki; Monika Bijata; Marta Pyskaty; Arthur Bikbaev; Martin Heine; Daniel Choquet; Leszek Kaczmarek; Jakub Wlodarczyk

    2014-01-01

    Synapses are particularly prone to dynamic alterations and thus play a major role in neuronal plasticity. Dynamic excitatory synapses are located at the membranous neuronal protrusions called dendritic spines. The ability to change synaptic connections involves both alterations at the morphological level and changes in postsynaptic receptor composition. We report that endogenous matrix metalloproteinase (MMP) activity promotes the structural and functional plasticity of local synapses by its ...

  13. The antidepressant-like effect of alarin is related to TrkB-mTOR signaling and synaptic plasticity.

    Science.gov (United States)

    Zhuang, Fuzhi; Li, Mei; Gao, Xin; Wang, Yun; Wang, Dongdong; Ma, Xing; Ma, Tengfei; Gu, Shuling

    2016-10-15

    Alarin is a newly derived neuropeptide from a splice variant of the galanin-like peptide gene. We previously showed that alarin has an antidepressant-like effect by increasing the activity of the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways, mediated by the tropomyosin-related kinase B receptor in the unpredictable chronic mild stress (UCMS) mouse model. Administration of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, prevents the rapid antidepressant-like effect induced by ketamine in animal models, indicating a vital role of mTOR in depression pathophysiology. mTOR is a target of the ERK and AKT pathways that regulates the initiation of protein translation via its downstream components: ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1). Therefore, we hypothesized that the antidepressant-like effects of alarin were achieved by activating ERK/AKT pathways, increasing the activity of mTOR and its downstream signaling components that contribute to protein synthesis required for synaptic plasticity. Our results suggest that intracerebroventricular administration of alarin significantly ameliorates depression-like behaviors in the UCMS mouse model. Furthermore, alarin restored UCMS-induced reductions of p70S6K and post-synaptic density 95 (PSD-95) mRNA levels, and of phospho-mTOR and phospho-4EBP1 in the prefrontal cortex, hippocampus, hypothalamus, and olfactory bulb. Additionally, alarin reversed the UCMS-induced downregulation of PSD-95 and synapsin I protein expression in these brain regions. Thus, the antidepressant-like effects of alarin may be mediated by restoring decreased activity of the mTOR signaling pathway and expression of synaptic proteins. Our findings help advance the understanding of depression pathophysiology. PMID:27374162

  14. Chronic intermittent hypoxia-induced deficits in synaptic plasticity and neurocognitive functions: a role for brain-derived neurotrophic factor

    Institute of Scientific and Technical Information of China (English)

    Hui XIE; Wing-ho YUNG

    2012-01-01

    Obstructive sleep apnea (OSA) is well known for its metabolic as well as neurobehavioral consequences.Chronic intermittent hypoxia (IH) is a major component of OSA.In recent years,substantial advances have been made in elucidating the cellular and molecular mechanisms underlying the effect of chronic IH on neurocognitive functions,many of which are based on studies in animal models.A number of hypotheses have been put forward to explain chronic IH-induced neurological dysfunctions.Among these,the roles of oxidative stress and apoptosis-related neural injury are widely accepted.Here,focusing on results derived from animal studies,we highlight a possible role of reduced expression of brain-derived neurotrophic factor (BDNF) in causing impairment in long-term synaptic plasticity and neurocognitive functions during chronic IH.The possible relationship between BDNF and previous findings on this subject will be elucidated.

  15. The NO-cGMP-PKG Signaling Pathway Regulates Synaptic Plasticity and Fear Memory Consolidation in the Lateral Amygdala via Activation of ERK/MAP Kinase

    Science.gov (United States)

    Ota, Kristie T.; Pierre, Vicki J.; Ploski, Jonathan E.; Queen, Kaila; Schafe, Glenn E.

    2008-01-01

    Recent studies have shown that nitric oxide (NO) signaling plays a crucial role in memory consolidation of Pavlovian fear conditioning and in synaptic plasticity in the lateral amygdala (LA). In the present experiments, we examined the role of the cGMP-dependent protein kinase (PKG), a downstream effector of NO, in fear memory consolidation and…

  16. Hypermethylation of Hippocampal Synaptic Plasticity-Related genes is Involved in Neonatal Sevoflurane Exposure-Induced Cognitive Impairments in Rats.

    Science.gov (United States)

    Ju, Ling-sha; Jia, Min; Sun, Jie; Sun, Xiao-ru; Zhang, Hui; Ji, Mu-huo; Yang, Jian-jun; Wang, Zhong-yun

    2016-02-01

    General anesthetics given to immature rodents cause delayed neurobehavioral abnormalities via incompletely understood mechanisms. DNA methylation, one of the epigenetic modifications, is essential for the modulation of hippocampal synaptic plasticity through regulating the related genes. Therefore, we investigated whether abnormalities in the hippocampal DNA methylation of synaptic plasticity-related genes are involved in neonatal sevoflurane exposure-induced cognitive impairments in rats. Male Sprague-Dawley rats were exposed to 3 % sevoflurane or 30 % oxygen/air for 2 h daily from postnatal day 7 (P7) to P9 and were treated with DNA methyltransferases (DNMTs) inhibitor 5-aza-2-deoxycytidine (5-AZA) or vehicle 1 h before the first sevoflurane exposure on P7. The rats were euthanized 1, 6, 24 h, and 30 days after the last sevoflurane exposure, and the brain tissues were harvested for biochemical analysis. Cognitive functions were evaluated by the open field, fear conditioning, and Morris water maze (MWM) tests on P39, P41-43, and P50-57, respectively. In the present study, repeated neonatal sevoflurane exposure resulted in hippocampus-dependent cognitive impairments as assessed by fear conditioning and MWM tests. The cognitive impairments were associated with the increased DNMTs and hypermethylation of brain-derived neurotrophic factor (BDNF) and Reelin genes, and subsequent down-regulation of BDNF and Reelin genes, which finally led to the decrease of dendritic spines in the hippocampal pyramidal neurons in adolescent rats. Notably, pretreatment with 5-AZA reversed these sevoflurane-induced abnormalities. In conclusion, our results suggest that hypermethylation of hippocampal BDNF and Reelin is involved in neonatal sevoflurane exposure-induced cognitive impairments.

  17. Enhanced group II mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala

    Directory of Open Access Journals (Sweden)

    Bird Gary C

    2006-05-01

    Full Text Available Abstract Background The latero-capsular part of the central nucleus of the amygdala (CeLC is the target of the spino-parabrachio-amygdaloid pain pathway. Our previous studies showed that CeLC neurons develop synaptic plasticity and increased neuronal excitability in the kaolin/carrageenan model of arthritic pain. These pain-related changes involve presynaptic group I metabotropic glutamate receptors (mGluRs and postsynaptic NMDA and calcitonin gene-related peptide (CGRP1 receptors. Here we address the role of group II mGluRs. Results Whole-cell current- and voltage-clamp recordings were made from CeLC neurons in brain slices from control rats and arthritic rats (>6 h postinjection of kaolin/carrageenan into the knee. Monosynaptic excitatory postsynaptic currents (EPSCs were evoked by electrical stimulation of afferents from the pontine parabrachial (PB area. A selective group II mGluR agonist (LY354740 decreased the amplitude of EPSCs more potently in CeLC neurons from arthritic rats (IC50 = 0.59 nM than in control animals (IC50 = 15.0 nM. The inhibitory effect of LY354740 was reversed by a group II mGluR antagonist (EGLU but not a GABAA receptor antagonist (bicuculline. LY354740 decreased frequency, but not amplitude, of miniature EPSCs in the presence of TTX. No significant changes of neuronal excitability measures (membrane slope conductance and action potential firing rate were detected. Conclusion Our data suggest that group II mGluRs act presynaptically to modulate synaptic plasticity in the amygdala in a model of arthritic pain.

  18. EFFECT OF ELECTROACUPUNCTURE ON SYNAPTIC PLASTICITY OF HPPOCAMPAL NEURONS IN CEREBRAL ISCHEMIA RATS

    Institute of Scientific and Technical Information of China (English)

    杨卓欣; 于海波; 王玲; 张家维

    2004-01-01

    Objective:To observe the effect of electroacupuncture (EA) on synaptic structure of hippocampal nerve felts and synaptophysin(SYN)expression in rats with cerebral ischemic injury. Methods: Sixty Wistar rats were randomized into sham-operation group, cerebral ischemia (CI) group and EA group, each of which was further divided into 1week (W) and 5W subgroups. CI injury model was established by occlusion of the bilateral common carotid arteries. "Baihui"(百会 GV 20), "Dazhui" (大椎 GV 14), "Renzhong"(人中 GV 26) and "Guanyuan"(关元 CV 4) were punctured and stimulated electrically. The brain tissue sections containing hippocampus region were stained with immunohistochemical technique and observed under light microscope and transmission electronic microscope. Results: After CI, the ischemic injury as degeneration of the presynapse compositions, decrease of the synaptic numeral density, and low expression of SYN were observed in hippocampal CA1 area. By the 5th week after CI, the neonatal synapses of CI and EA groups appeared, and SYN expression was upregulated. In EA group, the recovery of the numeral density of synapses was especially noticeable, being 93.8% of that of sham-operation group and significantly higher than that in CI group (P<0.01). Compared with sham-operation group, the calibrated optical density (COD) values of SYN increased to 70% in CI group, and 93.3% in EA group, and COD value in EA group was significantly higher than that in CI group (P<0.01). Conclusion: EA can function in promoting synaptic regeneration and enhancing and perfecting the actions of the reconstructed synapses in hippocampal CA1 area in CI rats.

  19. Dopamine and Norepinephrine Receptors Participate in Methylphenidate Enhancement of In Vivo Hippocampal Synaptic Plasticity

    OpenAIRE

    Jenson, Daniel; Yang, Kechun; Acevedo-Rodriguez, Alexandra; Levine, Amber; Broussard, John I.; Tang, Jianrong; Dani, John A.

    2014-01-01

    Attention-deficit hyperactive disorder (ADHD) is the most commonly studied and diagnosed psychiatric disorder in children. Methylphenidate (MPH, e.g., Ritalin) has been used to treat ADHD for over 50 years. It is the most commonly prescribed treatment for ADHD, and in the past decade it was the drug most commonly prescribed to teenagers. In addition, MPH has become one of the most widely abused drugs on college campuses. In this study, we examined the effects of MPH on hippocampal synaptic pl...

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

    Science.gov (United States)

    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.

  1. Ovariectomy does not exacerbate the negative effects of sleep deprivation on synaptic plasticity in rats.

    Science.gov (United States)

    Hajali, Vahid; Sheibani, Vahid; Mahani, Saeed E; Hajializadeh, Zahra; Shabani, Mohammad; Aliabadi, Hamzeh P; Saadati, Hakimeh; Esmaeilpour, Khadijeh

    2015-05-15

    In our previous work, we found that female rats showed more cognitive impairment than male rats following 72h sleep deprivation (SD). Here, we compared the intact female with ovariectomized (OVX) rats to assess the potential modulatory effects of endogenous female sex hormones against the 48h SD-induced cognitive and synaptic modulations. The multiple platform method was applied for SD induction and spatial performances were determined using Morris water maze (MWM) task. Early longterm potentiation (E-LTP) was evaluated in area CA1 of the hippocampus and PCR and western blotting assays were employed to assess hippocampal BDNF gene and protein expression. To reveal any influence of sleep loss on stress level, we also measured the plasma corticosterone levels of animals. Regardless of reproductive status, SD significantly impaired short-term memory and LTP, but did not significantly change the BDNF expression in the hippocampus. The corticosterone levels were decreased in both intact and OVX female rats following SD. These findings suggest that depletion of female sex steroid hormones does not lead to any heightened responsivity of female animals to the negative effects of SD on cognitive and synaptic functions. PMID:25748255

  2. ATM protein is located on presynaptic vesicles and its deficit leads to failures in synaptic plasticity.

    Science.gov (United States)

    Vail, Graham; Cheng, Aifang; Han, Yu Ray; Zhao, Teng; Du, Shengwang; Loy, Michael M T; Herrup, Karl; Plummer, Mark R

    2016-07-01

    Ataxia telangiectasia is a multisystemic disorder that includes a devastating neurodegeneration phenotype. The ATM (ataxia-telangiectasia mutated) protein is well-known for its role in the DNA damage response, yet ATM is also found in association with cytoplasmic vesicular structures: endosomes and lysosomes, as well as neuronal synaptic vesicles. In keeping with this latter association, electrical stimulation of the Schaffer collateral pathway in hippocampal slices from ATM-deficient mice does not elicit normal long-term potentiation (LTP). The current study was undertaken to assess the nature of this deficit. Theta burst-induced LTP was reduced in Atm(-/-) animals, with the reduction most pronounced at burst stimuli that included 6 or greater trains. To assess whether the deficit was associated with a pre- or postsynaptic failure, we analyzed paired-pulse facilitation and found that it too was significantly reduced in Atm(-/-) mice. This indicates a deficit in presynaptic function. As further evidence that these synaptic effects of ATM deficiency were presynaptic, we used stochastic optical reconstruction microscopy. Three-dimensional reconstruction revealed that ATM is significantly more closely associated with Piccolo (a presynaptic marker) than with Homer1 (a postsynaptic marker). These results underline how, in addition to its nuclear functions, ATM plays an important functional role in the neuronal synapse where it participates in the regulation of presynaptic vesicle physiology. PMID:27075534

  3. Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp

    Directory of Open Access Journals (Sweden)

    Abigail Mariga

    2015-12-01

    Full Text Available One of the cardinal features of neural development and adult plasticity is the contribution of activity-dependent signaling pathways. However, the interrelationships between different activity-dependent genes are not well understood. The immediate early gene neuronal-activity-regulated pentraxin (NPTX2 or Narp encodes a protein that has been associated with excitatory synaptogenesis, AMPA receptor aggregation, and the onset of critical periods. Here, we show that Narp is a direct transcriptional target of brain-derived neurotrophic factor (BDNF, another highly regulated activity-dependent gene involved in synaptic plasticity. Unexpectedly, Narp is bidirectionally regulated by BDNF. Acute BDNF withdrawal results in downregulation of Narp, whereas transcription of Narp is greatly enhanced by BDNF. Furthermore, our results show that BDNF directly regulates Narp to mediate glutamatergic transmission and mossy fiber plasticity. Hence, Narp serves as a significant epistatic target of BDNF to regulate synaptic plasticity during periods of dynamic activity.

  4. Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

    Science.gov (United States)

    Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

    2009-01-01

    Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

  5. Short-term versus long-term water maze training effects on hippocampal neuronal synaptic plasticity in a rat model of senile dementia

    Institute of Scientific and Technical Information of China (English)

    Guogui Li

    2008-01-01

    BACKGROUND: Changes in synaptic plasticity might underlie senile dementia, and might be the neurobiological basis for learning and memory dysfunctions in patients with Alzheimer's Disease. OBJECTIVE: To investigate the effects of water maze training on hippocampal neuronal synaptic plasticity in rats with senile dementia, and to compare changes in synaptic plasticity between short- and long-term water maze training sessions.DESIGN, TIME AND SETTING: A randomized, controlled, neuromorphological observation with animal models of senile dementia was performed at the laboratory of College of Pharmacy, Chongqing Medical University between November 2006 and April 2007.MATERIALS: Fifty male, Sprague Dawley rats were randomized into five groups, with 10 rats per group: model, control, sham-operated, short-term water maze training, and long-term water maze training. METHODS: In the model group, senile dementia was induced by fimbria-fornix lesion method. The control rats remained untreated. In the sham-operated group, water maze training was performed without fimbria-fornix lesion induction. Rats from the short-term water maze training group underwent 20-day water maze training from day 26 after fimbria-fornix lesion induction. The long-term water maze training group underwent 40-day water maze training beginning at day 6 following fimbria-fornix lesion induction. Beginning at day 41, each group underwent 5-day spatial learning and memory training. MAIN OUTCOME MEASURES: Following experimentation, the morphological parameters of synapses, including synaptic numerical density, synaptic surface density, and the average synapse size were stereologically measured. Through the use of an electron microscope, synaptic morphological changes in the hippocampai CA3 region were observed.RESULTS: Compared with the control group, synaptic numerical and surface densities were significantly decreased in the model group (P < 0.01). Synaptic numerical and surface densities significantly

  6. Histone Deacetylase (HDAC) Inhibitors - emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration.

    Science.gov (United States)

    Ganai, Shabir Ahmad; Ramadoss, Mahalakshmi; Mahadevan, Vijayalakshmi

    2016-01-01

    Epigenetic regulation of neuronal signalling through histone acetylation dictates transcription programs that govern neuronal memory, plasticity and learning paradigms. Histone Acetyl Transferases (HATs) and Histone Deacetylases (HDACs) are antagonistic enzymes that regulate gene expression through acetylation and deacetylation of histone proteins around which DNA is wrapped inside a eukaryotic cell nucleus. The epigenetic control of HDACs and the cellular imbalance between HATs and HDACs dictate disease states and have been implicated in muscular dystrophy, loss of memory, neurodegeneration and autistic disorders. Altering gene expression profiles through inhibition of HDACs is now emerging as a powerful technique in therapy. This review presents evolving applications of HDAC inhibitors as potential drugs in neurological research and therapy. Mechanisms that govern their expression profiles in neuronal signalling, plasticity and learning will be covered. Promising and exciting possibilities of HDAC inhibitors in memory formation, fear conditioning, ischemic stroke and neural regeneration have been detailed. PMID:26487502

  7. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants.

    Science.gov (United States)

    Duman, Ronald S; Aghajanian, George K; Sanacora, Gerard; Krystal, John H

    2016-03-01

    Depression is a common, devastating illness. Current pharmacotherapies help many patients, but high rates of a partial response or no response, and the delayed onset of the effects of antidepressant therapies, leave many patients inadequately treated. However, new insights into the neurobiology of stress and human mood disorders have shed light on mechanisms underlying the vulnerability of individuals to depression and have pointed to novel antidepressants. Environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology, resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function. Although current antidepressants, such as serotonin-reuptake inhibitors, produce subtle changes that take effect in weeks or months, it has recently been shown that treatment with new agents results in an improvement in mood ratings within hours of dosing patients who are resistant to typical antidepressants. Within a similar time scale, these new agents have also been shown to reverse the synaptic deficits caused by stress. PMID:26937618

  8. Ionotropic receptors at hippocampal mossy fibres: roles in axonal excitability, synaptic transmission and plasticity

    Directory of Open Access Journals (Sweden)

    Arnaud J Ruiz

    2013-01-01

    Full Text Available Dentate granule cells process information from the enthorinal cortex en route to the hippocampus proper. These neurons have a very negative resting membrane potential and are relatively silent in the slice preparation. They are also subject to strong feed-forward inhibition. Their unmyelinated axon or mossy fibre ramifies extensively in the hilus and projects to stratum lucidum where it makes giant en-passant boutons with CA3 pyramidal neurons. There is compelling evidence that mossy fibre boutons express presynaptic GABAA receptors, which are commonly found in granule cell dendrites. There is also suggestive evidence for the presence of other ionotropic receptors, including glycine, NMDA and kainate receptors, in mossy fibre boutons. These presynaptic receptors have been proposed to lead to mossy fibre membrane depolarisation. How this phenomenon alters the excitability of synaptic boutons, the shape of presynaptic action potentials, Ca2+ influx and neurotransmitter release has remained elusive, but high-resolution live imaging of individual varicosities and direct patch-clamp recordings have begun to shed light on these phenomena. Presynaptic GABAA and kainate receptors have also been reported to facilitate the induction of long-term potentiation at mossy fibre – CA3 synapses. Although mossy fibres are highly specialised, some of the principles emerging at this connection may apply elsewhere in the CNS.

  9. Synaptic plasticity and gravity: Ultrastructural, biochemical and physico-chemical fundamentals

    Science.gov (United States)

    Rahmann, H.; Slenzka, K.; Körtje, K. H.; Hilbig, R.

    On the basis of quantitative disturbances of the swimming behaviour of aquatic vertebrates (``loop-swimming'' in fish and frog larvae) following long-term hyper-g-exposure the question was raised whether or not and to what extent changes in the gravitational vector might influence the CNS at the cellular level. Therefore, by means of histological, histochemical and biochemical analyses the effect of 2-4 x g for 9 days on the gross morphology of the fish brain, and on different neuronal enzymes was investigated. In order to enable a more precise analysis in future-μg-experiments of any gravity-related effects on the neuronal synapses within the gravity-perceptive integration centers differentiated electron-microscopical and electronspectroscopical techniques have been developed to accomplish an ultrastructural localization of calcium, a high-affinity Ca2+-ATPase, creatine kinase and cytochrome oxidase. In hyper-g animals vs. 1-g controls, a reduction of total brain volume (15 %), a decrease in creatine kinase activity (20 %), a local increase in cytochrome oxidase activity, but no differences in Ca2+/Mg2+-ATPase activities were observed. Ultrastructural peculiarities of synaptic contact formation in gravity-related integration centers (Nucleus magnocellularis) were found. These results are discussed on the basis of a direct effect of hyper-gravity not only on the gravity-sensitive neuronal integration centers but possibly also on the physico-chemical properties of the lipid bilayer of neuronal membranes in general.

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27534901

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27534901

  13. On the correlation between reservoir metrics and performance for time series classification under the influence of synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Joseph Chrol-Cannon

    Full Text Available Reservoir computing provides a simpler paradigm of training recurrent networks by initialising and adapting the recurrent connections separately to a supervised linear readout. This creates a problem, though. As the recurrent weights and topology are now separated from adapting to the task, there is a burden on the reservoir designer to construct an effective network that happens to produce state vectors that can be mapped linearly into the desired outputs. Guidance in forming a reservoir can be through the use of some established metrics which link a number of theoretical properties of the reservoir computing paradigm to quantitative measures that can be used to evaluate the effectiveness of a given design. We provide a comprehensive empirical study of four metrics; class separation, kernel quality, Lyapunov's exponent and spectral radius. These metrics are each compared over a number of repeated runs, for different reservoir computing set-ups that include three types of network topology and three mechanisms of weight adaptation through synaptic plasticity. Each combination of these methods is tested on two time-series classification problems. We find that the two metrics that correlate most strongly with the classification performance are Lyapunov's exponent and kernel quality. It is also evident in the comparisons that these two metrics both measure a similar property of the reservoir dynamics. We also find that class separation and spectral radius are both less reliable and less effective in predicting performance.

  14. On the correlation between reservoir metrics and performance for time series classification under the influence of synaptic plasticity.

    Science.gov (United States)

    Chrol-Cannon, Joseph; Jin, Yaochu

    2014-01-01

    Reservoir computing provides a simpler paradigm of training recurrent networks by initialising and adapting the recurrent connections separately to a supervised linear readout. This creates a problem, though. As the recurrent weights and topology are now separated from adapting to the task, there is a burden on the reservoir designer to construct an effective network that happens to produce state vectors that can be mapped linearly into the desired outputs. Guidance in forming a reservoir can be through the use of some established metrics which link a number of theoretical properties of the reservoir computing paradigm to quantitative measures that can be used to evaluate the effectiveness of a given design. We provide a comprehensive empirical study of four metrics; class separation, kernel quality, Lyapunov's exponent and spectral radius. These metrics are each compared over a number of repeated runs, for different reservoir computing set-ups that include three types of network topology and three mechanisms of weight adaptation through synaptic plasticity. Each combination of these methods is tested on two time-series classification problems. We find that the two metrics that correlate most strongly with the classification performance are Lyapunov's exponent and kernel quality. It is also evident in the comparisons that these two metrics both measure a similar property of the reservoir dynamics. We also find that class separation and spectral radius are both less reliable and less effective in predicting performance.

  15. Effect of developmental lead exposure on synaptic plasticity and N—methyl—D—aspartate receptor subunit in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    RuanDY; SuiL

    2002-01-01

    Chronic lead(Pb) exposure is known to be associated with learning and memory,and cognitive dysfunction in children.Previous studies have demonstrated that Pb exposure may impair neuronal process underlying synaptic plasticity via a direct interaction with N-methyl-D-aspartate (NMDA) receptors(NMDARs).The studies described here were carried out to investigate effect of developmental Pb exposure on long-term potentiation(LTP),long-tern depression(LTD) and NMDAs subunits in rat hippocampus.The results are listed as follows:(1)low-level Pb exposture can impair the induction and maintenance of LTP in vivo and in vitro;(2)the Pb-induced impairment of LTD magnitude was an age-related decline in area CA1 of rat hippocampus;(3)chronic Pb exposure affected two components,voltage-gated calcium channel-dependent LTD and NMDARs-dependent LTD,of LTD induction in area CA1 of rat hippocampus;(4)different effects of developmental Pb exposure on NMDA receptor NR1,NR2A,NR2B,NR2C,NR2D and NR3A subunits in area CA1,CA2,CA3 and CA4 of rat hippocampus were observed;(5)the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors enriched in area CA1,CA3 and dentate gyrus and kainite receptors enriched in area CA1 and dentate gyrus of rat hippocampus were impaired by Pb exposure.

  16. ZD7288, a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity

    Institute of Scientific and Technical Information of China (English)

    Xiao-xue Zhang; Xiao-chun Min; Xu-lin Xu; Min Zheng; Lian-jun Guo

    2016-01-01

    The selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimeth-yl-6-(methylamino) pyrimidinium chloride (ZD7288) blocks the induction of long-term potentiation in the perforant path–CA3 region in rat hippocampusin vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path–CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hip-pocampal neurons using high performance liquid chromatography, and determined intracellular Ca2+ concentration ([Ca2+]i) using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspeciifc HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Further-more, ZD7288 attenuated glutamate-induced rises in [Ca2+]i in a concentration-dependent manner and reversed 8-Br-cAMP-mediated facilitation of these glutamate-induced [Ca2+]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both gluta-mate release and resultant [Ca2+]i increases in rat hippocampal neurons.

  17. Osthole improves synaptic plasticity in the hippocampus and cognitive function of Alzheimer's disease rats via regulating glutamate

    Institute of Scientific and Technical Information of China (English)

    Xiaohua Dong; Danshen Zhang; Li Zhang; Wei Li; Xianyong Meng

    2012-01-01

    Osthole,an effective monomer in Chinese medicinal herbs,can cross the blood-brain barrier and protect against brain injury,with few toxic effects.In this study,a rat model of Alzheimer's disease was established after intracerebroventricular injection of β-amyloid peptide (25-35).Subsequently,the rats were intraperitoneally treated with osthole (12.5 or 25.0 mg/kg) for 14 successive days.Results showed that osthole treatment significantly improved cognitive impairment and protected hippocampal neurons of Alzheimer's disease rats.Also,osthole treatment alleviated suppressed long-term potentiation in the hippocampus of Alzheimer's disease rats.In these osthole-treated Alzheimer's disease rats,the level of glutamate decreased,but there was no significant change in Y-amino-butyric acid.These experimental findings suggest that osthole can improve learning and memory impairment,and increase synaptic plasticity in Alzheimer's disease rats.These effects of osthole may be because of its regulation of central glutamate and Y-amino-butyric acid levels.

  18. Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1

    Directory of Open Access Journals (Sweden)

    Eadie Brennan D

    2009-02-01

    Full Text Available Abstract Background Cognitive deficits are a hallmark feature of both Down Syndrome (DS and Alzheimer's Disease (AD. Extra copies of the genes on chromosome 21 may also play an important role in the accelerated onset of AD in DS individuals. Growing evidence suggests an important function for cholesterol in the pathogenesis of AD, particularly in APP metabolism and production of Aβ peptides. The ATP-Binding Cassette-G1 (ABCG1 transporter is located on chromosome 21, and participates in the maintenance of tissue cholesterol homeostasis. Results To assess the role of ABCG1 in DS-related cognition, we evaluated the cognitive performance of mice selectively over-expressing the ABCG1 gene from its endogenous regulatory signals. Both wild-type and ABCG1 transgenic mice performed equivalently on several behavioral tests, including measures of anxiety, as well as on reference and working memory tasks. No deficits in hippocampal CA1 synaptic plasticity as determined with electrophysiological studies were apparent in mice over-expressing ABCG1. Conclusion These findings indicate that although ABCG1 may play a role in maintaining cellular or tissue cholesterol homeostasis, it is unlikely that excess ABCG1 expression contributes to the cognitive deficits in DS individuals.

  19. Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain.

    Science.gov (United States)

    Ramos-Moreno, Tania; Galazo, Maria J; Porrero, Cesar; Martínez-Cerdeño, Verónica; Clascá, Francisco

    2006-01-01

    Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.

  20. Use of multi-electrode array recordings in studies of network synaptic plasticity in both time and space

    Institute of Scientific and Technical Information of China (English)

    Ming-Gang Liu; Xue-Feng Chen; Ting He; Zhen Li; Jun Chen

    2012-01-01

    Simultaneous multisite recording using multi-electrode arrays (MEAs) in cultured and acutely-dissociated brain slices and other tissues is an emerging technique in the field of network electrophysiology.Over the past 40 years,great efforts have been made by both scientists and commercial concerns,to advance this technique.The MEA technique has been widely applied to many regions of the brain,retina,heart and smooth muscle in various studies at the network level.The present review starts from the development of MEA techniques and their uses in brain preparations,and then specifically concentrates on the use of MEA recordings in studies of synaptic plasticity at the network level in both the temporal and spatial domains.Because the MEA technique helps bridge the gap between single-cell recordings and behavioral assays,its wide application will undoubtedly shed light on the mechanisms underlying brain functions and dysfunctions at the network level that remained largely unknown due to the technical difficulties before it matured.

  1. Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK-3β Pathway and Notch Signaling Pathway in Rats.

    Science.gov (United States)

    Liu, Chunhua; Xu, Xiaxia; Gao, Jing; Zhang, Tao; Yang, Zhuo

    2016-08-01

    Our previous study has demonstrated that hydrogen sulfide (H2S) attenuates neuronal injury induced by vascular dementia (VD) in rats, but the mechanism is still poorly understood. In this study, we aimed to investigate whether the neuroprotection of H2S was associated with synaptic plasticity and try to interpret the potential underlying mechanisms. Adult male Wistar rats were suffered the ligation of bilateral common carotid arteries. At 24 h after surgery, rats were administered intraperitoneally with sodium hydrosulfide (NaHS, 5.6 mg·kg(-1)·day(-1)), a H2S donor, for 3 weeks in the VD+NaHS group and treated intraperitoneally with saline in the VD group respectively. Our results demonstrated that NaHS significantly decreased the level of glutamate. It obviously ameliorated cognitive flexibility as well as the spatial learning and memory abilities by Morris water maze. Moreover, NaHS significantly improved the long-term depression (LTD), and was able to elevate the expression of N-methyl-D-aspartate receptor subunit 2A, which plays a pivotal role in synaptic plasticity. Interestingly, NaHS decreased the phosphorylation of Akt, and it could maintain the activity of glycogen synthase kinase-3β (GSK-3β). Surprisingly, NaHS triggered the canonical Notch pathway by increasing expressions of Jagged-1 and Hes-1. These findings suggest that NaHS prevents synaptic plasticity from VD-induced damage partly via Akt/GSK-3β pathway and Notch signaling pathway.Hydrogen sulfide modulated the ratio of NMDAR 2A/2B and improved the synaptic plasticity via Akt/GSK-3β pathway and Notch signaling pathway in VD rats.

  2. Ras does not contribute to the facilitation of hippocampal synaptic plasticity enabled by environmental enrichment.

    Science.gov (United States)

    Novkovic, T; Heumann, R; Manahan-Vaughan, D

    2015-11-19

    Environmental enrichment (EE), which mimics the wealth of sensory, motor and cognitive stimuli that arise through intense interactions with the ambient environment, results in enhanced hippocampal long-term potentiation (LTP) and spatial learning. A key molecular factor in the mediation of these changes is the brain-derived neurotrophic factor (BDNF). One of the downstream cascades that is activated by BDNF is the cascade linked to the small GTPase, Ras, that triggers mitogen-activated protein kinase (MAPK) activity and is part of the cAMP response element-binding protein (CREB) pathway that can lead to synaptic restructuring to support LTP. Here, we explored whether persistent activation of Ras in neurons further enhances LTP following EE of rodents. Immediately following weaning, transgenic mice that expressed constitutively activated neuronal Ras, or their wildtype (Wt) littermates, underwent 3weeks of constant EE. In the absence of EE, theta burst stimulation (TBS) evoked LTP in the CA1 region of transgenic mice that was not significantly different from LTP in Wts. After 3weeks of EE, hippocampal LTP was improved in Wt mice. Enriched transgenic mice showed an equivalent level of LTP to enriched Wts, but it was not significantly different from non-enriched synRas controls. Western blot analysis performed after a pull-down assay showed that non-enriched transgenic mice expressed higher Ras activity compared to non-enriched Wts. Following EE, Ras activity was reduced in transgenics to levels detected in Wts. These results show that constitutive activation of Ras does not mimic the effects of EE on LTP. In addition, EE results in an equivalent enhancement of LTP transgenics and Wts, coupled with a decrease in Ras activity to Wt levels. This suggests that permanent activation of Ras in neurons of synRas animals following EE results in an altered feedback regulation of endogenous Ras activity that is not a key factor in LTP enhancements. The maintenance of Ras within

  3. Rapid eye movement sleep deprivation revives a form of developmentally regulated synaptic plasticity in the visual cortex of post-critical period rats.

    Science.gov (United States)

    Shaffery, James P; Lopez, Jorge; Bissette, Garth; Roffwarg, Howard P

    2006-01-01

    The critical period for observing a developmentally regulated form of synaptic plasticity in the visual cortex of young rats normally ends at about postnatal day 30. This developmentally regulated form of in vitro long-term potentiation (LTP) can be reliably induced in layers II-III by aiming high frequency, theta burst stimulation (TBS) at the white matter situated directly below visual cortex (LTPWM-III). Previous work has demonstrated that suppression of sensory activation of visual cortex, achieved by rearing young rats in total darkness from birth, delays termination of the critical period for inducing LTPWM-III. Subsequent data also demonstrated that when rapid eye movement sleep (REMS) is suppressed, thereby reducing REMS cortical activation, just prior to the end of the critical period, termination of this developmental phase is delayed, and LTPWM-III can still be reliably produced in the usual post-critical period. Here, we report that for approximately 3 weeks immediately following the usual end of the critical period, suppression of REMS disrupts the maturational processes that close the critical period, and LTPWM-III is readily induced in brain slices taken from these somewhat older animals. Insofar as in vitro LTP is a model for the cellular and molecular changes that underlie developmental synaptic plasticity, these results suggest that mechanisms of synaptic plasticity, which participate in brain development and perhaps also in learning and memory processes, remain susceptible to the effects of REMS deprivation during the general period of adolescence in the rat.

  4. Lrp4 domains differentially regulate limb/brain development and synaptic plasticity.

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    Theresa Pohlkamp

    Full Text Available Apolipoprotein E (ApoE genotype is the strongest predictor of Alzheimer's Disease (AD risk. ApoE is a cholesterol transport protein that binds to members of the Low-Density Lipoprotein (LDL Receptor family, which includes LDL Receptor Related Protein 4 (Lrp4. Lrp4, together with one of its ligands Agrin and its co-receptors Muscle Specific Kinase (MuSK and Amyloid Precursor Protein (APP, regulates neuromuscular junction (NMJ formation. All four proteins are also expressed in the adult brain, and APP, MuSK, and Agrin are required for normal synapse function in the CNS. Here, we show that Lrp4 is also required for normal hippocampal plasticity. In contrast to the closely related Lrp8/Apoer2, the intracellular domain of Lrp4 does not appear to be necessary for normal expression and maintenance of long-term potentiation at central synapses or for the formation and maintenance of peripheral NMJs. However, it does play a role in limb development.

  5. Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning.

    Science.gov (United States)

    Stelly, Claire E; Pomrenze, Matthew B; Cook, Jason B; Morikawa, Hitoshi

    2016-01-01

    Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences. Here, we show that repeated social defeat stress in rats causes persistent enhancement of long-term potentiation (LTP) of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA). Protein kinase A-dependent increase in the potency of inositol 1,4,5-triphosphate-induced Ca(2+) signaling underlies LTP facilitation. Notably, defeated rats display enhanced learning of contextual cues paired with cocaine experience assessed using a conditioned place preference (CPP) paradigm. Enhancement of LTP in the VTA and cocaine CPP in behaving rats both require glucocorticoid receptor activation during defeat episodes. These findings suggest that enhanced glutamatergic plasticity in the VTA may contribute, at least partially, to increased addiction vulnerability following repeated stressful experiences. PMID:27374604

  6. Tinnitus: pathology of synaptic plasticity at the cellular and system levels

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    Matthieu J Guitton

    2012-03-01

    Full Text Available Despite being more and more common, and having a high impact on the quality of life of sufferers, tinnitus does not yet have a cure. This has been mostly the result of limited knowledge of the biological mechanisms underlying this adverse pathology. However, the last decade has witnessed tremendous progress in our understanding on the pathophysiology of tinnitus. Animal models have demonstrated that tinnitus is a pathology of neural plasticity, and has two main components: a molecular, peripheral component related to the initiation phase of tinnitus; and a system-level, central component related to the long-term maintenance of tinnitus. Using the most recent experimental data and the molecular/system dichotomy as a framework, we describe here the biological basis of tinnitus. We then discuss these mechanisms from an evolutionary perspective, highlighting similarities with memory. Finally, we consider how these discoveries can translate into therapies, and we suggest operative strategies to design new and effective combined therapeutic solutions using both pharmacological (local and systemic and behavioral tools (e.g., using tele-medicine and virtual reality settings.

  7. Neonatal proinflammatory challenge in male Wistar rats: Effects on behavior, synaptic plasticity, and adrenocortical stress response.

    Science.gov (United States)

    Tishkina, Anna; Stepanichev, Mikhail; Kudryashova, Irina; Freiman, Sofia; Onufriev, Mikhail; Lazareva, Natalia; Gulyaeva, Natalia

    2016-05-01

    Effects of neonatal proinflammatory stress (NPS) on the development of anxiety and depressive-like behavior, stress responsiveness, hippocampal plasticity and conditioned fear response were studied in adolescent and adult male Wistar rats. On PND 3 and PND 5, the pups were subcutaneously injected with bacterial lipopolysaccharide (LPS, 50 μg/kg). In the open field test, signs of increased anxiety were demonstrated in adolescent (PND 32), but not in adult (PND 101) rats. In the elevated plus maze, no changes could be detected in adolescent rats, however, in the adults the number of entries into the open arms decreased suggesting increased anxiety after NPS. Signs of "behavioral despair" in the forced swim test, expressed in adolescent rats as a trend, became significant in the adults indicating depression-like behavior. In the majority of brain slices from PND 19-PND 33 rats subjected to NPS, deficit of LTP in the hippocampal CA1 field was detected, this deficit being associated with the impaired mechanisms of LTP induction. In the adult rats, NPS enhanced fear conditioning promoting improved formation of the novel context-foot shock association in the contextual fear conditioning paradigm without effect on cued fear conditioning. NPS significantly impaired functioning of the hypothalamic-pituitary-adrenal axis (HPAA), resulting in an elevated corticosterone level maintained in the adolescents but not in the adults and in modified corticosterone response to behavioral sub-chronic stress in both adolescent and adult rats. Thus, NPS induces "perinatal malprogramming" resulting in development of depression-like behaviors, associated with abnormalities in functioning of the HPAA, impaired hippocampal neuroplasticity (LTP) and changes in hippocampus-dependent memory formation. PMID:26851557

  8. GABAA Receptor-Mediated Bidirectional Control of Synaptic Activity, Intracellular Ca2+, Cerebral Blood Flow, and Oxygen Consumption in Mouse Somatosensory Cortex In Vivo

    DEFF Research Database (Denmark)

    Jessen, Sanne Barsballe; Brazhe, Alexey; Lind, Barbara Lykke;

    2015-01-01

    concentrations of THIP suppressed ΔCBF and ΔCMRO2 at high stimulation frequencies. Zolpidem had similar but less-pronounced effects, with similar dependence on drug concentration and stimulation frequency. Our present findings suggest that slight increases in both synaptic and extrasynaptic GABAAR activity might......Neural activity regulates local increases in cerebral blood flow (ΔCBF) and the cortical metabolic rate of oxygen (ΔCMRO2) that constitutes the basis of BOLD functional neuroimaging signals. Glutamate signaling plays a key role in brain vascular and metabolic control; however, the modulatory effect...

  9. Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia.

    Science.gov (United States)

    Nie, Jingjing; Yang, Xiaosu; Tang, Qingping; Shen, Qin; Li, Simin

    2016-01-01

    It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats. PMID:26556240

  10. A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice.

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    Alexander Kurz

    Full Text Available BACKGROUND: Parkinson's disease (PD, the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA. PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD was absent in corticostriatal slices from old transgenic mice. CONCLUSIONS/SIGNIFICANCE: Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches.

  11. Effects of genistein on cognitive dysfunction and hippocampal synaptic plasticity impairment in an ovariectomized rat kainic acid model of seizure.

    Science.gov (United States)

    Khodamoradi, Mehdi; Asadi-Shekaari, Majid; Esmaeili-Mahani, Saeed; Esmaeilpour, Khadije; Sheibani, Vahid

    2016-09-01

    The major objective of this study was to investigate the probable effects of genistein (one of the most important soy phytoestrogens-SPEs) on seizure-induced cognitive dysfunction, hippocampal early long-term potentiation (E-LTP) impairment and morphological damage to CA1 neurons in ovariectomized (OVX) rats. Three weeks after ovariectomy, cannulae were implanted over the left lateral ventricle. After a 7-day recovery period, animals were injected by genistein (0.5 or 5mg/kg) or vehicle during four consecutive days, each 24h. One h after the last treatment, kainic acid (KA) or vehicle was perfused into the left lateral ventricle to induce generalized tonic-clonic seizures. Finally, 7 days later, spatial learning and memory of animals were examined using the Morris water maze (MWM) task, hippocampal E-LTP was assessed using in-vivo field potential recordings and the morphology of hippocampal CA1 area was examined using Fluoro-Jade C staining. KA-induced generalized seizures resulted in spatial learning and memory impairment, E-LTP deficit and CA1 cell injury. Seizure-induced abnormalities improved partially only by the lower dose of genistein (0.5mg/kg). However, genistein at the higher dose (5mg/kg) did not have any beneficial effects. Also, genistein did not affect seizure activity. It is concluded that genistein may have partially preventive effects against seizure-induced cognitive impairment in OVX rats. Also, it seems that such effects of genistein are correlated with its beneficial effects on hippocampal synaptic plasticity and morphology. PMID:27235295

  12. Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors

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    Xie Yongling

    2012-02-01

    Full Text Available Abstract Background Nanomaterials, as a new kind of materials, have been greatly applied in different fields due to their special properties. With the industrialization of nanostructured materials and increasing public exposure, the biosafety and potential influences on central nervous system (CNS have received more attention. Nanosized zinc oxide (nanoZnO was suggested to up-regulate neuronal excitability and to induce glutamate release in vitro. Therefore, we hypothesized nanoparticles of nanoZnO may lead to changes in balance of neurotransmitter or neuronal excitability of CNS. This study was to investigate if there were effects of nanoZnO on animal model of depression. Methods Male Swiss mice were given lipopolysaccharides (LPS, 100 μg/kg, 100 μg/ml, every other day, 8 times, i.p. from weaning to induce depressive-like behaviors. NanoZnO (5.6 mg/kg, 5.6 mg/ml, every other day, 8 times, i.p. was given as the interaction. The mouse model was characterized using the methods of open field test, tail suspension test and forced swim test. Furthermore, the spatial memory was evaluated using Morris water maze (MWM and the synaptic plasticity was assessed by measuring the long-term potentiation (LTP in the perforant pathway (PP to dentate gyrus (DG in vivo. Results Results indicated that model mice showed disrupted spatial memory and LTP after LPS injections and the behavioral and electrophysiological improvements after nanoZnO treatment. Conclusion Data suggested that nanoZnO may play some roles in CNS of mental disorders, which could provide some useful direction on the new drug exploring and clinical researches.

  13. A realistic neural mass model of the cortex with laminar-specific connections and synaptic plasticity - evaluation with auditory habituation.

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    Peng Wang

    Full Text Available In this work we propose a biologically realistic local cortical circuit model (LCCM, based on neural masses, that incorporates important aspects of the functional organization of the brain that have not been covered by previous models: (1 activity dependent plasticity of excitatory synaptic couplings via depleting and recycling of neurotransmitters and (2 realistic inter-laminar dynamics via laminar-specific distribution of and connections between neural populations. The potential of the LCCM was demonstrated by accounting for the process of auditory habituation. The model parameters were specified using Bayesian inference. It was found that: (1 besides the major serial excitatory information pathway (layer 4 to layer 2/3 to layer 5/6, there exists a parallel "short-cut" pathway (layer 4 to layer 5/6, (2 the excitatory signal flow from the pyramidal cells to the inhibitory interneurons seems to be more intra-laminar while, in contrast, the inhibitory signal flow from inhibitory interneurons to the pyramidal cells seems to be both intra- and inter-laminar, and (3 the habituation rates of the connections are unsymmetrical: forward connections (from layer 4 to layer 2/3 are more strongly habituated than backward connections (from Layer 5/6 to layer 4. Our evaluation demonstrates that the novel features of the LCCM are of crucial importance for mechanistic explanations of brain function. The incorporation of these features into a mass model makes them applicable to modeling based on macroscopic data (like EEG or MEG, which are usually available in human experiments. Our LCCM is therefore a valuable building block for future realistic models of human cognitive function.

  14. Reorganization of Learning-Associated Prefrontal Synaptic Plasticity between the Recall of Recent and Remote Fear Extinction Memory

    Science.gov (United States)

    Hugues, Sandrine; Garcia, Rene

    2007-01-01

    We have previously shown that fear extinction is accompanied by an increase of synaptic efficacy in inputs from the ventral hippocampus (vHPC) and mediodorsal thalamus (MD) to the medial prefrontal cortex (mPFC) and that disrupting these changes to mPFC synaptic transmission compromises extinction processes. The aim of this study was to examine…

  15. Microwave Exposure Impairs Synaptic Plasticity in the Rat Hippocampus and PC12 Cells through Over-activation of the NMDA Receptor Signaling Pathway

    Institute of Scientific and Technical Information of China (English)

    XIONG Lu; DONG Ji; YAO Bin Wei; ZHAO Li; PENG Rui Yun; SUN Cheng Feng; ZHANG Jing; GAO Ya Bing; WANG Li Feng; ZUO Hong Yan; WANG Shui Ming; ZHOU Hong Mei; XU Xin Ping

    2015-01-01

    Objective The aim of this study is to investigate whether microwave exposure would affect the N-methyl-D-aspartate receptor (NMDAR) signaling pathway to establish whether this plays a role in synaptic plasticity impairment. Methods 48 male Wistar rats were exposed to 30 mW/cm² microwave for 10 min every other day for three times. Hippocampal structure was observed through H&E staining and transmission electron microscope. PC12 cells were exposed to 30 mW/cm² microwave for 5 min and the synapse morphology was visualized with scanning electron microscope and atomic force microscope. The release of amino acid neurotransmitters and calcium influx were detected. The expressions of several key NMDAR signaling molecules were evaluated. Results Microwave exposure caused injury in rat hippocampal structure and PC12 cells, especially the structure and quantity of synapses. The ratio of glutamic acid and gamma-aminobutyric acid neurotransmitters was increased and the intracellular calcium level was elevated in PC12 cells. A significant change in NMDAR subunits (NR1, NR2A, and NR2B) and related signaling molecules (Ca2+/calmodulin-dependent kinase II gamma and phosphorylated cAMP-response element binding protein) were examined. Conclusion 30 mW/cm² microwave exposure resulted in alterations of synaptic structure, amino acid neurotransmitter release and calcium influx. NMDAR signaling molecules were closely associated with impaired synaptic plasticity.

  16. miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity.

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    Judit Remenyi

    Full Text Available miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity.

  17. Apolipoprotein E4 impairs in vivo hippocampal long-term synaptic plasticity by reducing the phosphorylation of CaMKIIα and CREB.

    Science.gov (United States)

    Qiao, Feng; Gao, Xiu-Ping; Yuan, Li; Cai, Hong-Yan; Qi, Jin-Shun

    2014-01-01

    Inheritance of the apolipoprotein E genotype ε4 (APOE4) is a powerful risk factor for most cases of late-onset Alzheimer's disease (AD). However, the effects of ApoE4 on the long-term synaptic plasticity and its underlying mechanism have not clearly investigated. In the present study, we examined the effects of ApoE4 on the hippocampal late-phase long-term potentiation (L-LTP) and investigated its probable molecular mechanisms by using in vivo field potential recording, immunohistochemistry, and western blotting. The results showed that: (1) intra-hippocampal injection of 0.2 μg ApoE4, but not ApoE2, before high frequency stimulations (HFSs) attenuated the induction of hippocampal L-LTP in the CA1 region, while injection of the same concentration of ApoE4 after HFSs, even at a higher concentration (2 μg), did not affect the long term synaptic plasticity; (2) ApoE4 injection did not affect the paired pulse facilitation in the hippocampal CA1 region; (3) ApoE4 injection before, not after, HFSs significantly decreased the levels of phosphorylated Ca2+/calmodulin-dependent protein kinase IIα (p-CaMKIIα) and phosphorylated cAMP response element-binding protein (p-CREB) in the hippocampus. These results demonstrated for the first time that ApoE4 could impair hippocampal L-LTP by reducing p-CaMKIIα and p-CREB, suggesting that the ApoE4-induced suppression of hippocampal long-term synaptic plasticity may contribute to the cognitive impairments in genetic AD; and both CaMKIIα and CREB are important intracellular targets of the neurotoxic ApoE4.

  18. Depression as a Glial-Based Synaptic Dysfunction

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    Daniel eRial

    2016-01-01

    Full Text Available Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processing occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the ‘quad-partite’ synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increase microglia ‘activation’ in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, BDNF affect glia functioning, whereas antidepressant treatments (SSRIs, electroshock, deep brain stimulation recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication - such as the purinergic neuromodulation system operated by ATP and adenosine - emerge as promising candidates to re-normalize synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression.

  19. Bis(propyl)-cognitin Prevents β-amyloid-induced Memory Deficits as Well as Synaptic Formation and Plasticity Impairments via the Activation of PI3-K Pathway.

    Science.gov (United States)

    Jiang, Liting; Huang, Meng; Xu, Shujun; Wang, Yu; An, Pengyuan; Feng, Chenxi; Chen, Xiaowei; Wei, Xiaofei; Han, Yifan; Wang, Qinwen

    2016-08-01

    Bis(propyl)-cognitin (B3C), derived from tacrine linked with three methylene (-CH2-) groups, is a dimerized molecule interacting multiple targets. During the past several years, it has been reported as a promising therapeutic drug for Alzheimer's disease (AD) and other neurodegenerative disorders. However, the therapeutic mechanism of B3C for AD needs further demonstration. Based on a combination of behavioral tests, electrophysiological technique, immunocytochemistry, and live cell imaging, we studied the effects and the underlying mechanism of B3C on the impairments of cognitive function, synapse formation, and synaptic plasticity induced by soluble amyloid-β protein (Aβ) oligomers. Our study showed that spatial learning and memory in a Morris water maze task and recognition memory in a novel object recognition task were significantly decreased in the AD model mice created by hippocampal injection of Aβ. Chronic administration of B3C for 21 days prevented the memory impairments of the AD model mice in a dose-dependent manner. Live cell imaging study showed that 2-h pretreatment of B3C prevented the decrease in the number of filopodia and synapses induced by Aβ (0.5 μM) in a dose-dependent manner. Besides, electrophysiological recording data showed that the inhibition of long-term potentiation (LTP) induced by Aβ1-42 oligomers in the dentate gyrus (DG) of hippocampus was prevented by B3C in a dose-dependent manner. Furthermore, we found that the neuroprotective effect of B3C against Aβ-oligomer-induced impairments of synaptic formation and plasticity could be partially blocked by a specific phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 (50 μM). Therefore, these results indicate that B3C can prevent Aβ-oligomer-induced cognitive deficits, synaptic formation impairments, and synaptic plasticity impairments in a concentration-dependent manner. These effects of B3C are partially mediated via the PI3-K pathway. This study provides novel insights

  20. Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

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    Aisa N. Chepkova

    2015-01-01

    Full Text Available Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old to old (18–24 months of age animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age. Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

  1. Drebrin depletion alters neurotransmitter receptor levels in protein complexes, dendritic spine morphogenesis and memory-related synaptic plasticity in the mouse hippocampus.

    Science.gov (United States)

    Jung, Gangsoo; Kim, Eun-Jung; Cicvaric, Ana; Sase, Sunetra; Gröger, Marion; Höger, Harald; Sialana, Fernando Jayson; Berger, Johannes; Monje, Francisco J; Lubec, Gert

    2015-07-01

    Drebrin an actin-bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a regulator of hippocampal glutamatergic activity which is critical for memory formation and maintenance. Here, we examined the effects of genetic deletion of drebrin on dendritic spine and on the level of complexes containing major brain receptors. To this end, homozygous and heterozygous drebrin knockout mice generated in our laboratory and related wild-type control animals were studied. Level of protein complexes containing dopamine receptor D1/dopamine receptor D2, 5-hydroxytryptamine receptor 1A (5-HT1(A)R), and 5-hydroxytryptamine receptor 7 (5-HT7R) were significantly reduced in hippocampus of drebrin knockout mice whereas no significant changes were detected for GluR1, 2, and 3 and NR1 as examined by native gel-based immunoblotting. Drebrin depletion also altered dendritic spine formation, morphology, and reduced levels of dopamine receptor D1 in dendritic spines as evaluated using immunohistochemistry/confocal microscopy. Electrophysiological studies further showed significant reduction in memory-related hippocampal synaptic plasticity upon drebrin depletion. These findings provide unprecedented experimental support for a role of drebrin in the regulation of memory-related synaptic plasticity and neurotransmitter receptor signaling, offer relevant information regarding the interpretation of previous studies and help in the design of future studies on dendritic spines.

  2. Simulation of synaptic short-term plasticity using Ba(CF3SO3)2-doped polyethylene oxide electrolyte film

    Science.gov (United States)

    Chang, C. T.; Zeng, F.; Li, X. J.; Dong, W. S.; Lu, S. H.; Gao, S.; Pan, F.

    2016-01-01

    The simulation of synaptic plasticity using new materials is critical in the study of brain-inspired computing. Devices composed of Ba(CF3SO3)2-doped polyethylene oxide (PEO) electrolyte film were fabricated and with pulse responses found to resemble the synaptic short-term plasticity (STP) of both short-term depression (STD) and short-term facilitation (STF) synapses. The values of the charge and discharge peaks of the pulse responses did not vary with input number when the pulse frequency was sufficiently low(~1 Hz). However, when the frequency was increased, the charge and discharge peaks decreased and increased, respectively, in gradual trends and approached stable values with respect to the input number. These stable values varied with the input frequency, which resulted in the depressed and potentiated weight modifications of the charge and discharge peaks, respectively. These electrical properties simulated the high and low band-pass filtering effects of STD and STF, respectively. The simulations were consistent with biological results and the corresponding biological parameters were successfully extracted. The study verified the feasibility of using organic electrolytes to mimic STP.

  3. Simulation of synaptic short-term plasticity using Ba(CF3SO3)2-doped polyethylene oxide electrolyte film.

    Science.gov (United States)

    Chang, C T; Zeng, F; Li, X J; Dong, W S; Lu, S H; Gao, S; Pan, F

    2016-01-01

    The simulation of synaptic plasticity using new materials is critical in the study of brain-inspired computing. Devices composed of Ba(CF3SO3)2-doped polyethylene oxide (PEO) electrolyte film were fabricated and with pulse responses found to resemble the synaptic short-term plasticity (STP) of both short-term depression (STD) and short-term facilitation (STF) synapses. The values of the charge and discharge peaks of the pulse responses did not vary with input number when the pulse frequency was sufficiently low(~1 Hz). However, when the frequency was increased, the charge and discharge peaks decreased and increased, respectively, in gradual trends and approached stable values with respect to the input number. These stable values varied with the input frequency, which resulted in the depressed and potentiated weight modifications of the charge and discharge peaks, respectively. These electrical properties simulated the high and low band-pass filtering effects of STD and STF, respectively. The simulations were consistent with biological results and the corresponding biological parameters were successfully extracted. The study verified the feasibility of using organic electrolytes to mimic STP. PMID:26739613

  4. Role of mast cell- and non-mast cell-derived inflammatory mediators in immunologic induction of synaptic plasticity

    Directory of Open Access Journals (Sweden)

    A.A.C. Albuquerque

    1997-07-01

    Full Text Available We have previously discovered a long-lasting enhancement of synaptic transmission in mammal autonomic ganglia caused by immunological activation of ganglionic mast cells. Subsequent to mast cell activation, lipid and peptide mediators are released which may modulate synaptic function. In this study we determined whether some mast cell-derived mediators, prostaglandin D2 (PGD2; 1.0 µM, platelet aggregating factor (PAF; 0.3 µM and U44619 (a thromboxane analogue; 1.0 µM, and also endothelin-1 (ET-1; 0.5 µM induce synaptic potentiation in the guinea pig superior cervical ganglion (SCG, and compared their effects on synaptic transmission with those induced by a sensitizing antigen, ovalbumin (OVA; 10 µg/ml. The experiments were carried out on SCGs isolated from adult male guinea pigs (200-250 g actively sensitized to OVA, maintained in oxygenated Locke solution at 37oC. Synaptic potentiation was measured through alterations of the integral of the post-ganglionic compound action potential (CAP. All agents tested caused long-term (LTP; duration ³30 min or short-term (STP; <30 min potentiation of synaptic efficacy, as measured by the increase in the integral of the post-ganglionic CAP. The magnitude of mediator-induced potentiation was never the same as the antigen-induced long-term potentiation (A-LTP. The agent that best mimicked the antigen was PGD2, which induced a 75% increase in CAP integral for LTP (antigen: 94% and a 34% increase for STP (antigen: 91%. PAF-, U44619-, and ET-1-induced increases in CAP integral ranged for LTP from 34 to 47%, and for STP from 0 to 26%. These results suggest that the agents investigated may participate in the induction of A-LTP

  5. Orchestrated regulation of Nogo receptors, LOTUS, AMPA receptors and BDNF in an ECT model suggests opening and closure of a window of synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Max Nordgren

    Full Text Available Electroconvulsive therapy (ECT is an efficient and relatively fast acting treatment for depression. However, one severe side effect of the treatment is retrograde amnesia, which in certain cases can be long-term. The mechanisms behind the antidepressant effect and the amnesia are not well understood. We hypothesized that ECT causes transient downregulation of key molecules needed to stabilize synaptic structure and to prevent Ca2+ influx, and a simultaneous increase in neurotrophic factors, thus providing a short time window of increased structural synaptic plasticity. Here we followed regulation of NgR1, NgR3, LOTUS, BDNF, and AMPA subunits GluR1 and GluR2 flip and flop mRNA levels in hippocampus at 2, 4, 12, 24, and 72 hours after a single episode of induced electroconvulsive seizures (ECS in rats. NgR1 and LOTUS mRNA levels were transiently downregulated in the dentate gyrus 2, 4, 12 and 4, 12, 24 h after ECS treatment, respectively. GluR2 flip, flop and GluR1 flop were downregulated at 4 h. GluR2 flip remained downregulated at 12 h. In contrast, BDNF, NgR3 and GluR1 flip mRNA levels were upregulated. Thus, ECS treatment induces a transient regulation of factors important for neuronal plasticity. Our data provide correlations between ECS treatment and molecular events compatible with the hypothesis that both effects and side effects of ECT may be caused by structural synaptic rearrangements.

  6. Synaptic plasticity and NO-cGMP-PKG signaling regulate pre- and postsynaptic alterations at rat lateral amygdala synapses following fear conditioning.

    Directory of Open Access Journals (Sweden)

    Kristie T Ota

    Full Text Available In vertebrate models of synaptic plasticity, signaling via the putative "retrograde messenger" nitric oxide (NO has been hypothesized to serve as a critical link between functional and structural alterations at pre- and postsynaptic sites. In the present study, we show that auditory Pavlovian fear conditioning is associated with significant and long-lasting increases in the expression of the postsynaptically-localized protein GluR1 and the presynaptically-localized proteins synaptophysin and synapsin in the lateral amygdala (LA within 24 hrs following training. Further, we show that rats given intra-LA infusion of either the NR2B-selective antagonist Ifenprodil, the NOS inhibitor 7-Ni, or the PKG inhibitor Rp-8-Br-PET-cGMPS exhibit significant decreases in training-induced expression of GluR1, synaptophysin, and synapsin immunoreactivity in the LA, while those rats infused with the PKG activator 8-Br-cGMP exhibit a significant increase in these proteins in the LA. In contrast, rats given intra-LA infusion of the NO scavenger c-PTIO exhibit a significant decrease in synapsin and synaptophysin expression in the LA, but no significant impairment in the expression of GluR1. Finally, we show that intra-LA infusions of the ROCK inhibitor Y-27632 or the CaMKII inhibitor KN-93 impair training-induced expression of GluR1, synapsin, and synaptophysin in the LA. These findings suggest that the NO-cGMP-PKG, Rho/ROCK, and CaMKII signaling pathways regulate fear memory consolidation, in part, by promoting both pre- and post-synaptic alterations at LA synapses. They further suggest that synaptic plasticity in the LA during auditory fear conditioning promotes alterations at presynaptic sites via NO-driven "retrograde signaling".

  7. Metabolic demand stimulates CREB signaling in the limbic cortex: implication for the induction of hippocampal synaptic plasticity by intrinsic stimulus for survival

    Directory of Open Access Journals (Sweden)

    Nelly M Estrada

    2009-06-01

    Full Text Available Caloric restriction by fasting has been implicated to facilitate synaptic plasticity and promote contextual learning. However, cellular and molecular mechanisms underlying the effect of fasting on memory consolidation are not completely understood. We hypothesized that fasting-induced enhancement of synaptic plasticity was mediated by the increased signaling mediated by CREB (c-AMP response element binding protein, an important nuclear protein and the transcription factor that is involved in the consolidation of memories in the hippocampus. In the in vivo rat model of 18 h fasting, the expression of phosphorylated CREB (pCREB was examined using anti-phospho-CREB (Ser133 in cardially-perfused and cryo-sectioned rat brain specimens. When compared with control animals, the hippocampus exhibited up to a two-fold of increase in pCREB expression in fasted animals. The piriform cortex, the entorhinal cortex, and the cortico-amygdala transitional zone also significantly increased immunoreactivities to pCREB. In contrast, the amygdala did not show any change in the magnitude of pCREB expression in response to fasting. The arcuate nucleus in the medial hypothalamus, which was previously reported to up-regulate CREB phosphorylation during fasting of up to 48 h, was also strongly immunoreactive and provided a positive control in the present study. Our findings demonstrate a metabolic demand not only stimulates cAMP-dependent signaling cascades in the hypothalamus, but also signals to various limbic brain regions including the hippocampus by activating the CREB signaling mechanism. The hippocampus is a primary brain structure for learning and memory. It receives hypothalamic and arcuate projections directly from the fornix. The hippocampus is also situated centrally for functional interactions with other limbic cortexes by establishing reciprocal synaptic connections. We suggest that hippocampal neurons and those in the surrounding limbic cortexes are

  8. Synaptic electronics: materials, devices and applications.

    Science.gov (United States)

    Kuzum, Duygu; Yu, Shimeng; Wong, H-S Philip

    2013-09-27

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented.

  9. Synaptic electronics: materials, devices and applications

    International Nuclear Information System (INIS)

    In this paper, the recent progress of synaptic electronics is reviewed. The basics of biological synaptic plasticity and learning are described. The material properties and electrical switching characteristics of a variety of synaptic devices are discussed, with a focus on the use of synaptic devices for neuromorphic or brain-inspired computing. Performance metrics desirable for large-scale implementations of synaptic devices are illustrated. A review of recent work on targeted computing applications with synaptic devices is presented. (topical review)

  10. Gravin orchestrates protein kinase A and β2-adrenergic receptor signaling critical for synaptic plasticity and memory

    NARCIS (Netherlands)

    Havekes, Robbert; Canton, David A; Park, Alan J; Huang, Ted; Nie, Ting; Day, Jonathan P; Guercio, Leonardo A; Grimes, Quinn; Luczak, Vincent; Gelman, Irwin H; Baillie, George S; Scott, John D; Abel, Ted

    2012-01-01

    A kinase-anchoring proteins (AKAPs) organize compartmentalized pools of protein kinase A (PKA) to enable localized signaling events within neurons. However, it is unclear which of the many expressed AKAPs in neurons target PKA to signaling complexes important for long-lasting forms of synaptic plast

  11. Nicotine uses neuron-glia communication to enhance hippocampal synaptic transmission and long-term memory.

    Directory of Open Access Journals (Sweden)

    Mónica López-Hidalgo

    Full Text Available Nicotine enhances synaptic transmission and facilitates long-term memory. Now it is known that bi-directional glia-neuron interactions play important roles in the physiology of the brain. However, the involvement of glial cells in the effects of nicotine has not been considered until now. In particular, the gliotransmitter D-serine, an endogenous co-agonist of NMDA receptors, enables different types of synaptic plasticity and memory in the hippocampus. Here, we report that hippocampal long-term synaptic plasticity induced by nicotine was annulled by an enzyme that degrades endogenous D-serine, or by an NMDA receptor antagonist that acts at the D-serine binding site. Accordingly, both effects of nicotine: the enhancement of synaptic transmission and facilitation of long-term memory were eliminated by impairing glial cells with fluoroacetate, and were restored with exogenous D-serine. Together, these results show that glial D-serine is essential for the long-term effects of nicotine on synaptic plasticity and memory, and they highlight the roles of glial cells as key participants in brain functions.

  12. SAHA enhances synaptic function and plasticity in vitro but has limited brain availability in vivo and does not impact cognition.

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    Jesse E Hanson

    Full Text Available Suberoylanilide hydroxamic acid (SAHA is an inhibitor of histone deacetylases (HDACs used for the treatment of cutaneous T cell lymphoma (CTCL and under consideration for other indications. In vivo studies suggest reducing HDAC function can enhance synaptic function and memory, raising the possibility that SAHA treatment could have neurological benefits. We first examined the impacts of SAHA on synaptic function in vitro using rat organotypic hippocampal brain slices. Following several days of SAHA treatment, basal excitatory but not inhibitory synaptic function was enhanced. Presynaptic release probability and intrinsic neuronal excitability were unaffected suggesting SAHA treatment selectively enhanced postsynaptic excitatory function. In addition, long-term potentiation (LTP of excitatory synapses was augmented, while long-term depression (LTD was impaired in SAHA treated slices. Despite the in vitro synaptic enhancements, in vivo SAHA treatment did not rescue memory deficits in the Tg2576 mouse model of Alzheimer's disease (AD. Along with the lack of behavioral impact, pharmacokinetic analysis indicated poor brain availability of SAHA. Broader assessment of in vivo SAHA treatment using high-content phenotypic characterization of C57Bl6 mice failed to demonstrate significant behavioral effects of up to 150 mg/kg SAHA following either acute or chronic injections. Potentially explaining the low brain exposure and lack of behavioral impacts, SAHA was found to be a substrate of the blood brain barrier (BBB efflux transporters Pgp and Bcrp1. Thus while our in vitro data show that HDAC inhibition can enhance excitatory synaptic strength and potentiation, our in vivo data suggests limited brain availability may contribute to the lack of behavioral impact of SAHA following peripheral delivery. These results do not predict CNS effects of SAHA during clinical use and also emphasize the importance of analyzing brain drug levels when interpreting

  13. Maternal separation prior to neonatal hypoxia-ischemia: Impact on emotional aspects of behavior and markers of synaptic plasticity in hippocampus.

    Science.gov (United States)

    Markostamou, Ioanna; Ioannidis, Anestis; Dandi, Evgenia; Mandyla, Maria-Aikaterini; Nousiopoulou, Evangelia; Simeonidou, Constantina; Spandou, Evangelia; Tata, Despina A

    2016-08-01

    Exposure to early-life stress is associated with long-term alterations in brain and behavior, and may aggravate the outcome of neurological insults. This study aimed at investigating the possible interaction between maternal separation, a model of early stress, and subsequent neonatal hypoxia-ischemia on emotional behavior and markers of synaptic plasticity in hippocampus. Therefore, rat pups (N=60) were maternally separated for a prolonged (MS 180min) or a brief (MS 15min) period during the first six postnatal days, while a control group was left undisturbed. Hypoxia-ischemia was applied to a subgroup of each rearing condition on postnatal day 7. Emotional behavior was examined at three months of age and included assessments of anxiety (elevated plus maze), depression-like behavior (forced swimming) and spontaneous exploration (open field). Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in CA3 and dentate gyrus hippocampal regions. We found that neonatal hypoxia-ischemia caused increased levels of anxiety, depression-like behavior and locomotor activity (ambulation). Higher anxiety levels were also seen in maternally separated rats (MS180min) compared to non-maternally separated rats, but prolonged maternal separation prior to HI did not potentiate the HI-associated effect. No differences among the three rearing conditions were found regarding depression-like behavior or ambulation. Immunohistochemical evaluation of synaptophysin revealed that both prolonged maternal separation (MS180min) and neonatal hypoxia-ischemia significantly reduced its expression in the CA3 and dentate gyrus. Decreases in synaptophysin expression in these areas were not exacerbated in rats that were maternally separated for a prolonged period prior to HI. Regarding BDNF expression, we found a significant decrease in immunoreactivity only in the hypoxic-ischemic rats that were subjected to the prolonged maternal separation paradigm. The above findings suggest

  14. Stress-Induced Enhancement of Mouse Amygdalar Synaptic Plasticity Depends on Glucocorticoid and ß-Adrenergic Activity

    OpenAIRE

    Ratna Angela Sarabdjitsingh; Daniel Kofink; Henk Karst; E. Ron de Kloet; Marian Joëls

    2012-01-01

    BACKGROUND: Glucocorticoid hormones, in interaction with noradrenaline, enable the consolidation of emotionally arousing and stressful experiences in rodents and humans. Such interaction is thought to occur at least partly in the basolateral nucleus of the amygdala (BLA) which is crucially involved in emotional memory formation. Extensive evidence points to long-term synaptic potentiation (LTP) as a mechanism contributing to memory formation. Here we determined in adolescent C57/Bl6 mice the ...

  15. Lead Exposure Impairs Hippocampus Related Learning and Memory by Altering Synaptic Plasticity and Morphology During Juvenile Period.

    Science.gov (United States)

    Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing

    2016-08-01

    Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes. PMID:26141123

  16. Reversible Recruitment of a Homeostatic Reserve Pool of Synaptic Vesicles Underlies Rapid Homeostatic Plasticity of Quantal Content.

    Science.gov (United States)

    Wang, Xueyong; Pinter, Martin J; Rich, Mark M

    2016-01-20

    Homeostatic regulation is essential for the maintenance of synaptic strength within the physiological range. The current study is the first to demonstrate that both induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds of blocking or unblocking acetylcholine receptors at the mouse neuromuscular junction. Our data suggest that the homeostatic upregulation of release is due to Ca(2+)-dependent increase in the size of the readily releasable pool (RRP). Blocking vesicle refilling prevented upregulation of quantal content (QC), while leaving baseline release relatively unaffected. This suggested that the upregulation of QC was due to mobilization of a distinct pool of vesicles that were rapidly recycled and thus were dependent on continued vesicle refilling. We term this pool the "homeostatic reserve pool." A detailed analysis of the time course of vesicle release triggered by a presynaptic action potential suggests that the homeostatic reserve pool of vesicles is normally released more slowly than other vesicles, but the rate of their release becomes similar to that of the major pool during homeostatic upregulation of QC. Remarkably, instead of finding a generalized increase in the recruitment of vesicles into RRP, we identified a distinct homeostatic reserve pool of vesicles that appear to only participate in synchronized release following homeostatic upregulation of QC. Once this small pool of vesicles is depleted by the block of vesicle refilling, homeostatic upregulation of QC is no longer observed. This is the first identification of the population of vesicles responsible for the blockade-induced upregulation of release previously described. Significance statement: The current study is the first to demonstrate that both the induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds. Our data suggest that homeostatic upregulation of release is due to Ca(2+)-dependent

  17. Expression pattern of neural synaptic plasticity marker-Arc in different brain regions induced by conditioned drug withdrawal from acute morphine-dependent rats

    Institute of Scientific and Technical Information of China (English)

    Mu LI; Yuan-yuan HOU; Bin LU; Jie CHEN; Zhi-qiang CHI; Jing-gen LIU

    2009-01-01

    Aim: The immediate early gene Arc (activity-regulated cytoskeletal-associated protein) mRNA and protein are induced by strong synaptic activation and rapidly transported into dendrites, where they localize at active synaptic sites. Thus, the Arc mRNA and protein are proposed as a marker of neuronal reactivity to map the neural substrates that are recruited by vari-ous stimuli. In the present study, we examined the expression of Arc protein induced by conditioned naloxone-precipitated drug withdrawal in different brain regions of acute morphine-dependent rats. The objective of the present study was to address the specific neural circuits involved in conditioned place aversion (CPA) that has not yet been well characterized. Methods: Place aversion was elicited by conditioned naloxone-precipitated drug withdrawal following exposure to a single dose of morphine. An immunohistochemical method was employed to detect the expression of Arc, which was used as a plasticity marker to trace the brain areas that contribute to the formation of the place aversion. Results: Marked increases in Arc protein levels were found in the medial and lateral prefrontal cortex, the sensory cortex, the lateral striatum and the amygdala. This effect was more pronounced in the basolateral arnygdala (BLA), the central nucleus of the amygdala (CeA), and the bed nucleus of the striatal terminals (BNST) when compared with the control group.Conclusion: Our results suggest that these brain regions may play key roles In mediating the negative motivational compo-nent of opiate withdrawal.

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

    Science.gov (United States)

    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. PMID:19937070

  19. Effect of short-term exposure to dichlorvos on synaptic plasticity of rat hippocampal slices: Involvement of acylpeptide hydrolase and α7 nicotinic receptors

    International Nuclear Information System (INIS)

    Dichlorvos is the active molecule of the pro-drug metrifonate used to revert the cognitive deficits associated with Alzheimer's disease. A few years ago it was reported that dichlorvos inhibits the enzyme acylpeptide hydrolase at lower doses than those necessary to inhibit acetylcholinesterase to the same extent. Therefore, the aim of our investigation was to test the hypothesis that dichlorvos can enhance synaptic efficacy through a mechanism that involves acylpeptide hydrolase instead of acetylcholinesterase inhibition. We used long-term potentiation induced in rat hippocampal slices as a model of synaptic plasticity. Our results indicate that short-term exposures (20 min) to 50 μM dichlorvos enhance long-term potentiation in about 200% compared to the control condition. This effect is correlated with approximately 60% inhibition of acylpeptide hydrolase activity, whereas acetylcholinesterase activity remains unaffected. Paired-pulse facilitation and inhibition experiments indicate that dichlorvos does not have any presynaptic effect in the CA3 → CA1 pathway nor affect gabaergic interneurons. Interestingly, the application of 100 nM methyllicaconitine, an α7 nicotinic receptor antagonist, blocked the enhancing effect of dichlorvos on long-term potentiation. These results indicate that under the exposure conditions described above, dichlorvos enhances long-term potentiation through a postsynaptic mechanism that involves (a) the inhibition of the enzyme acylpeptide hydrolase and (b) the modulation of α7 nicotinic receptors.

  20. The free radical scavenger Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance in a mouse model of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Oliwia Alicja Janc

    2014-02-01

    Full Text Available Rett syndrome (RS causes severe cognitive impairment, loss of speech, epilepsy, and breathing disturbances with intermittent hypoxia. Also mitochondria are affected; a subunit of respiratory complex III is dysregulated, the inner mitochondrial membrane is leaking protons, and brain ATP levels seem reduced. Our recent assessment of mitochondrial function in MeCP2-deficient mouse (Mecp2-/y hippocampus, confirmed early metabolic alterations, an increased oxidative burden, and a more vulnerable cellular redox balance. As these changes may contribute to the manifestation of symptoms and disease progression, we now evaluated whether free radical scavengers are capable of improving neuronal and mitochondrial function in RS. Acute hippocampal slices of adult mice were incubated with the vitamin E derivative Trolox for 3-5 h. In Mecp2-/y slices this treatment dampened neuronal hyperexcitability, improved short-term plasticity, and fully restored synaptic long-term potentiation. Furthermore, Trolox specifically attenuated the increased hypoxia susceptibility of Mecp2-/y slices. Also, the anticonvulsive effects of Trolox were assessed, but the severity of 4-aminopyridine provoked seizure-like discharges was not significantly affected. Adverse side effects of Trolox on mitochondria can be excluded, but clear indications for an improvement of mitochondrial function were not found. Since several ion-channels and neurotransmitter receptors are redox modulated, the mitochondrial alterations and the associated oxidative burden may contribute to the neuronal dysfunction in RS. We confirmed in Mecp2-/y hippocampus that Trolox dampens neuronal hyperexcitability, reinstates synaptic plasticity, and improves hypoxia tolerance. Therefore, radical scavengers are promising compounds for the treatment of neuronal dysfunction in RS and deserve further detailed evaluation.

  1. Impairment of L-type Ca2+ channel-dependent forms of hippocampal synaptic plasticity in mice deficient in the extracellular matrix glycoprotein tenascin-C.

    Science.gov (United States)

    Evers, Matthias R; Salmen, Benedikt; Bukalo, Olena; Rollenhagen, Astrid; Bösl, Michael R; Morellini, Fabio; Bartsch, Udo; Dityatev, Alexander; Schachner, Melitta

    2002-08-15

    The extracellular matrix glycoprotein tenascin-C (TN-C) has been suggested to play important functional roles during neural development, axonal regeneration, and synaptic plasticity. We generated a constitutively TN-C-deficient mouse mutant from embryonic stem cells with a floxed tn-C allele, representing a standard for future analysis of conditionally targeted mice. The gross morphology of the CNS was not detectably affected, including no evidence for perturbed nerve cell migration, abnormal oligodendrocyte distribution, or defective myelination. Despite the apparent normal histology of the hippocampus and normal performance in the water maze, theta-burst stimulation (TBS) of Schaffer collaterals elicited reduced long-term potentiation (LTP) in the CA1 region of TN-C-deficient mutants, as compared with wild-type littermates. However, high-frequency stimulation evoked normal LTP not only in CA1, but also at mossy fiber-CA3 and medial and lateral perforant path-granule cell synapses in the dentate gyrus. Low-frequency stimulation failed to induce long-term depression in the CA1 region of TN-C-deficient animals. Recordings of TBS-induced LTP in the presence of nifedipine, an antagonist of L-type voltage-dependent Ca2+ channels (VDCCs), did not affect LTP in TN-C-deficient mice, but reduced LTP in wild-type mice to the levels seen in mutants. Furthermore, chemical induction of a L-type VDCC-dependent LTP in the CA1 region by application of the K+ channel blocker tetraethylammonium resulted in impaired LTP in TN-C mutants. Thus, reduction in L-type VDCC-mediated signaling appears to mediate the deficits in certain forms of synaptic plasticity in constitutively TN-C-deficient mice. PMID:12177213

  2. Expression of microRNA-34a in Alzheimer's disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity.

    Science.gov (United States)

    Sarkar, S; Jun, S; Rellick, S; Quintana, D D; Cavendish, J Z; Simpkins, J W

    2016-09-01

    Polygenetic risk factors and reduced expression of many genes in late-onset Alzheimer's disease (AD) impedes identification of a target(s) for disease-modifying therapies. We identified a single microRNA, miR-34a that is over expressed in specific brain regions of AD patients as well as in the 3xTg-AD mouse model. Specifically, increased miR-34a expression in the temporal cortex region compared to age matched healthy control correlates with severity of AD pathology. miR-34a over expression in patient's tissue and forced expression in primary neuronal culture correlates with concurrent repression of its target genes involved in synaptic plasticity, oxidative phosphorylation and glycolysis. The repression of oxidative phosphorylation and glycolysis related proteins correlates with reduced ATP production and glycolytic capacity, respectively. We also found that miR-34a overexpressed neurons secrete miR-34a containing exosomes that are taken up by neighboring neurons. Furthermore, miR-34a targets dozens of genes whose expressions are known to be correlated with synchronous activity in resting state functional networks. Our analysis of human genomic sequences from the tentative promoter of miR-34a gene shows the presence of NFκB, STAT1, c-Fos, CREB and p53 response elements. Together, our results raise the possibilities that pathophysiology-induced activation of specific transcription factor may lead to increased expression of miR-34a gene and miR-34a mediated concurrent repression of its target genes in neural networks may result in dysfunction of synaptic plasticity, energy metabolism, and resting state network activity. Thus, our results provide insights into polygenetic AD mechanisms and disclose miR-34a as a potential therapeutic target for AD. PMID:27235866

  3. Brief subthreshold events can act as Hebbian signals for long-term plasticity.

    Directory of Open Access Journals (Sweden)

    Elodie Fino

    Full Text Available BACKGROUND: Action potentials are thought to be determinant for the induction of long-term synaptic plasticity, the cellular basis of learning and memory. However, neuronal activity does not lead systematically to an action potential but also, in many cases, to synaptic depolarizing subthreshold events. This is particularly exemplified in corticostriatal information processing. Indeed, the striatum integrates information from the whole cerebral cortex and, due to the membrane properties of striatal medium spiny neurons, cortical inputs do not systematically trigger an action potential but a wide range of subthreshold postsynaptic depolarizations. Accordingly, we have addressed the following question: does a brief subthreshold event act as a Hebbian signal and induce long-term synaptic efficacy changes? METHODOLOGY/PRINCIPAL FINDINGS: Here, using perforated patch-clamp recordings on rat brain corticostriatal slices, we demonstrate, that brief (30 ms subthreshold depolarizing events in quasi-coincidence with presynaptic activity can act as Hebbian signals and are sufficient to induce long-term synaptic plasticity at corticostriatal synapses. This "subthreshold-depolarization dependent plasticity" (SDDP induces strong, significant and bidirectional long-term synaptic efficacy changes at a very high occurrence (81% for time intervals between pre- and postsynaptic stimulations (Deltat of -110bidirectional long-term plasticity induced by brief subthreshold events paired with presynaptic activity. The existence of a subthreshold-depolarization dependent plasticity extends considerably, beyond the action potential, the neuron's capabilities to

  4. Stress-induced enhancement of mouse amygdalar synaptic plasticity depends on glucocorticoid and ß-adrenergic activity.

    Directory of Open Access Journals (Sweden)

    Ratna Angela Sarabdjitsingh

    Full Text Available BACKGROUND: Glucocorticoid hormones, in interaction with noradrenaline, enable the consolidation of emotionally arousing and stressful experiences in rodents and humans. Such interaction is thought to occur at least partly in the basolateral nucleus of the amygdala (BLA which is crucially involved in emotional memory formation. Extensive evidence points to long-term synaptic potentiation (LTP as a mechanism contributing to memory formation. Here we determined in adolescent C57/Bl6 mice the effects of stress on LTP in the LA-BLA pathway and the specific roles of corticosteroid and β-adrenergic receptor activation in this process. PRINCIPAL FINDINGS: Exposure to 20 min of restraint stress (compared to control treatment prior to slice preparation enhanced subsequent LTP induction in vitro, without affecting baseline fEPSP responses. The role of glucocorticoid receptors, mineralocorticoid receptors and β2-adrenoceptors in the effects of stress was studied by treating mice with the antagonists mifepristone, spironolactone or propranolol respectively (or the corresponding vehicles prior to stress or control treatment. In undisturbed controls, mifepristone and propranolol administration in vivo did not influence LTP induced in vitro. By contrast, spironolactone caused a gradually attenuating form of LTP, both in unstressed and stressed mice. Mifepristone treatment prior to stress strongly reduced the ability to induce LTP in vitro. Propranolol normalized the stress-induced enhancement of LTP to control levels during the first 10 min after high frequency stimulation, after which synaptic responses further declined. CONCLUSIONS: Acute stress changes BLA electrical properties such that subsequent LTP induction is facilitated. Both β-adrenergic and glucocorticoid receptors are involved in the development of these changes. Mineralocorticoid receptors are important for the maintenance of LTP in the BLA, irrespective of stress-induced changes in the

  5. Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: rapid reversal by anti-Aß agents.

    Science.gov (United States)

    Qi, Yingjie; Klyubin, Igor; Harney, Sarah C; Hu, NengWei; Cullen, William K; Grant, Marianne K; Steffen, Julia; Wilson, Edward N; Do Carmo, Sonia; Remy, Stefan; Fuhrmann, Martin; Ashe, Karen H; Cuello, A Claudio; Rowan, Michael J

    2014-12-24

    Long before synaptic loss occurs in Alzheimer's disease significant harbingers of disease may be detected at the functional level. Here we examined if synaptic long-term potentiation is selectively disrupted prior to extracellular deposition of Aß in a very complete model of Alzheimer's disease amyloidosis, the McGill-R-Thy1-APP transgenic rat. Longitudinal studies in freely behaving animals revealed an age-dependent, relatively rapid-onset and persistent inhibition of long-term potentiation without a change in baseline synaptic transmission in the CA1 area of the hippocampus. Thus the ability of a standard 200 Hz conditioning protocol to induce significant NMDA receptor-dependent short- and long-term potentiation was lost at about 3.5 months of age and this deficit persisted for at least another 2-3 months, when plaques start to appear. Consistent with in vitro evidence for a causal role of a selective reduction in NMDA receptor-mediated synaptic currents, the deficit in synaptic plasticity in vivo was associated with a reduction in the synaptic burst response to the conditioning stimulation and was overcome using stronger 400 Hz stimulation. Moreover, intracerebroventricular treatment for 3 days with an N-terminally directed monoclonal anti- human Aß antibody, McSA1, transiently reversed the impairment of synaptic plasticity. Similar brief treatment with the BACE1 inhibitor LY2886721 or the γ-secretase inhibitor MRK-560 was found to have a comparable short-lived ameliorative effect when tracked in individual rats. These findings provide strong evidence that endogenously generated human Aß selectively disrupts the induction of long-term potentiation in a manner that enables potential therapeutic options to be assessed longitudinally at the pre-plaque stage of Alzheimer's disease amyloidosis.

  6. EDITORIAL: Synaptic electronics Synaptic electronics

    Science.gov (United States)

    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    neuromorphic circuit composed of a nanoscale 1-kbit resistive random-access memory (RRAM) cross-point array of synapses and complementary metal-oxide-semiconductor (CMOS) neuron circuits [13]; a WO3-x-based nanoionics device from Masakazu Aono's group with a wide scale of reprogrammable memorization functions [14]; a new spike-timing dependent plasticity scheme based on a MOS transistor as a selector and a RRAM as a variable resistance device [15]; a new hybrid memristor-CMOS neuromorphic circuit [16]; and a photo-assisted atomic switch [17]. Synaptic electronics evidently has many emerging facets, and Duygu Kuzum, Shimeng Yu, and H-S Philip Wong in the US provide a review of the field, including the materials, devices and applications [18]. In embracing the expertise acquired over thousands of years of evolution, biomimetics and bio-inspired design is a common, smart approach to technological innovation. Yet in successfully mimicking the physiological mechanisms of the human mind synaptic electronics research has a potential impact that is arguably unprecedented. That the quirks and eccentricities recently unearthed in the behaviour of nanomaterials should lend themselves so accommodatingly to emulating synaptic functions promises some very exciting developments in the field, as the articles in this special issue emphasize. References [1] von Neumann J (ed) 2012 The Computer and the Brain 3rd edn (Yale: Yale University Press) [2] Strukov D B, Snider G S, Stewart D R and Williams R S 2008 The missing memristor found Nature 453 80-3 [3] Chua L O 1971 Memristor—the missing circuit element IEEE Trans. Circuit Theory 18 507-19 [4] Chua L O 2013 Memristor, Hodgkin-Huxley, and Edge of Chaos Nanotechnology 24 383001 [5] Pickett M D and Williams R S 2013 Phase transitions enable computational universality in neuristor-based cellular automata Nanotechnology 24 384002 [6] Cruz-Albrecht J M, Derosier T and Srinivasa N 2013 Scalable neural chip with synaptic electronics using CMOS

  7. Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement.

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    Hearing, Matthew C; Jedynak, Jakub; Ebner, Stephanie R; Ingebretson, Anna; Asp, Anders J; Fischer, Rachel A; Schmidt, Clare; Larson, Erin B; Thomas, Mark John

    2016-01-19

    Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drug-related behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortex-accumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies. PMID:26739562

  8. Impairment of cognitive function and synaptic plasticity associated with alteration of information flow in theta and gamma oscillations in melamine-treated rats.

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    Xiaxia Xu

    Full Text Available Changes of neural oscillations at a variety of physiological rhythms are effectively associated with cognitive performance. The present study investigated whether the directional indices of neural information flow (NIF could be used to symbolize the synaptic plasticity impairment in hippocampal CA3-CA1 network in a rat model of melamine. Male Wistar rats were employed while melamine was administered at a dose of 300 mg/kg/day for 4 weeks. Behavior was measured by the Morris water maze(MWMtest. Local field potentials (LFPs were recorded before long-term potentiation (LTP induction. Generalized partial directed coherence (gPDC and phase-amplitude coupling conditional mutual information (PAC_CMI were used to measure the unidirectional indices in both theta and low gamma oscillations (LG, ~ 30-50 Hz. Our results showed that melamine induced the cognition deficits consistent with the reduced LTP in CA1 area. Phase locking values (PLVs showed that the synchronization between CA3 and CA1 in both theta and LG rhythms was reduced by melamine. In both theta and LG rhythms, unidirectional indices were significantly decreased in melamine treated rats while a similar variation trend was observed in LTP reduction, implying that the effects of melamine on cognitive impairment were possibly mediated via profound alterations of NIF on CA3-CA1 pathway in hippocampus. The results suggested that LFPs activities at these rhythms were most likely involved in determining the alterations of information flow in the hippocampal CA3-CA1 network, which might be associated with the alteration of synaptic transmission to some extent.

  9. Synaptic plasticity in the hippocampus of a APP/PS1 mouse model of Alzheimer's disease is impaired in old but not young mice.

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    Simon Gengler

    Full Text Available BACKGROUND: Alzheimer disease (AD is a neurodegenerative disorder for which there is no cure. We have investigated synaptic plasticity in area CA1 in a novel AD mouse model (APPPS1-21 which expresses the Swedish mutation of APP and the L166P mutation of human PS-1. This model shows initial plaque formation at 2 months in the neocortex and 4 months in the hippocampus and displays beta-amyloid-associated pathologies and learning impairments. METHODOLOGY/PRINCIPAL FINDINGS: We tested long-term potentiation (LTP and short term potentiation (paired-pulse facilitation, PPF of synaptic transmission in vivo in area CA1 of the hippocampus. There was no difference in LTP or PPF at 4-5 months of age in APPPS1-21 mice compared to littermate controls. At 6 months of age there was also no difference in LTP but APPPS1-21 mice showed slightly increased PPF (p<0.03. In 8 months old mice, LTP was greatly impaired in APPPS-21 animals (p<0.0001 while PPF was not changed. At 15 months of age, APPPS1-21 mice showed again impaired LTP compared to littermate controls (p<0.005, and PPF was also significantly reduced at 80 ms (p<0.005 and 160 ms (p<0.01 interstimulus interval. Immunohistological analysis showed only modest amyloid deposition in the hippocampus at 4 and 6 months with a robust increase up to 15 months of age. CONCLUSIONS: Our results suggest that increased formation and aggregation of beta amyloid with aging is responsible for the impaired LTP with aging in this mouse model, while the transient increase of PPF at 6 months of age is caused by some other mechanism.

  10. Bidirectional coupling between astrocytes and neurons mediates learning and dynamic coordination in the brain: a multiple modeling approach.

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    John J Wade

    Full Text Available In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a "learning signal" to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity, and the modeling strategy may be extended to coordination among remote neuron clusters.

  11. VSNL1 Co-expression networks in aging include calcium signaling, synaptic plasticity, and Alzheimer’s disease pathways

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    C W Lin

    2015-03-01

    Full Text Available The Visinin-like 1 (VSNL1 gene encodes Visinin-like protein 1, a peripheral biomarker for Alzheimer disease (AD. Little is known, however, about normal VSNL1 expression in brain and the biologic networks in which it participates. Frontal cortex gray matter from 209 subjects without neurodegenerative or psychiatric illness, ranging in age from 16–91, were processed on Affymetrix GeneChip 1.1 ST and Human SNP Array 6.0. VSNL1 expression was unaffected by age and sex, and not significantly associated with SNPs in cis or trans. VSNL1 was significantly co-expressed with genes in pathways for Calcium Signaling, AD, Long Term Potentiation, Long Term Depression, and Trafficking of AMPA Receptors. The association with AD was driven, in part, by correlation with amyloid precursor protein (APP expression. These findings provide an unbiased link between VSNL1 and molecular mechanisms of AD, including pathways implicated in synaptic pathology in AD. Whether APP may drive increased VSNL1 expression, VSNL1 drives increased APP expression, or both are downstream of common pathogenic regulators will need to be evaluated in model systems.

  12. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits

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    Aungst, Stephanie L; Kabadi, Shruti V; Thompson, Scott M; Stoica, Bogdan A; Faden, Alan I

    2014-01-01

    Repeated mild traumatic brain injury (mTBI) can cause sustained cognitive and psychiatric changes, as well as neurodegeneration, but the underlying mechanisms remain unclear. We examined histologic, neurophysiological, and cognitive changes after single or repeated (three injuries) mTBI using the rat lateral fluid percussion (LFP) model. Repeated mTBI caused substantial neuronal cell loss and significantly increased numbers of activated microglia in both ipsilateral and contralateral hippocampus on post-injury day (PID) 28. Long-term potentiation (LTP) could not be induced on PID 28 after repeated mTBI in ex vivo hippocampal slices from either hemisphere. N-Methyl-D-aspartate (NMDA) receptor-mediated responses were significantly attenuated after repeated mTBI, with no significant changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated responses. Long-term potentiation was elicited in slices after single mTBI, with potentiation significantly increased in ipsilateral versus contralateral hippocampus. After repeated mTBI, rats displayed cognitive impairments in the Morris water maze (MWM) and novel object recognition (NOR) tests. Thus, repeated mTBI causes deficits in the hippocampal function and changes in excitatory synaptic neurotransmission, which are associated with chronic neuroinflammation and neurodegeneration. PMID:24756076

  13. An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model

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    Kempf, Stefan J.; Metaxas, Athanasios; Ibáñez-Vea, María; Darvesh, Sultan; Finsen, Bente; Larsen, Martin R.

    2016-01-01

    The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology. We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APPswe/PS1ΔE9 mice, particularly in the neocortex and olfactory bulb. This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, Aβ expression and neuroinflammation. We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease. PMID:27144524

  14. Phase-specific plasticity of synaptic structures in the somatosensory cortex of living mice during neuropathic pain

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    Kim Sun

    2011-11-01

    Full Text Available Abstract Background Postsynaptic dendritic spines in the cortex are highly dynamic, showing rapid morphological changes including elongation/retraction and formation/elimination in response to altered sensory input or neuronal activity, which achieves experience/activity-dependent cortical circuit rewiring. Our previous long-term in vivo two-photon imaging study revealed that spine turnover in the mouse primary somatosensory (S1 cortex markedly increased in an early development phase of neuropathic pain, but was restored in a late maintenance phase of neuropathic pain. However, it remains unknown how spine morphology is altered preceding turnover change and whether gain and loss of presynaptic boutons are changed during neuropathic pain. Findings Here we used short-term (2-hour and long-term (2-week time-lapse in vivo two-photon imaging of individual spines and boutons in the S1 cortical layer 1 of the transgenic mice expressing GFP in pyramidal neurons following partial sciatic nerve ligation (PSL. We found in the short-term imaging that spine motility (Δ length per 30 min significantly increased in the development phase of neuropathic pain, but returned to the baseline in the maintenance phase. Moreover, the proportion of immature (thin and mature (mushroom spines increased and decreased, respectively, only in the development phase. Long-term imaging data showed that formation and elimination of boutons moderately increased and decreased, respectively, during the first 3 days following PSL and was subsequently restored. Conclusions Our results indicate that the S1 synaptic structures are rapidly destabilized and rearranged following PSL and subsequently stabilized in the maintenance phase of neuropathic pain, suggesting a novel therapeutic target in intractable chronic pain.

  15. Signal enhancement in the output stage of the basal ganglia by synaptic short-term plasticity in the direct, indirect and hyper direct pathways

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    Mikael eLindahl

    2013-06-01

    Full Text Available Many of the synapses in the basal ganglia display short-term plasticity. Still, computational models have not yet been used to investigate how this affects signaling. Here we use a model of the basal ganglia network, constrained by available data, to quantitatively investigate how synaptic short-term plasticity affects the substantia nigra reticulata (SNr, the basal ganglia output nucleus. We find that SNr becomes particularly responsive to the characteristic burst-like activity seen in both direct and indirect pathway striatal medium spiny neurons (MSN. As expected by the standard model, direct pathway MSNs are responsible for decreasing the activity in SNr. In particular, our simulations indicate that bursting in only a few percent of the direct pathway MSNs is sufficient for completely inhibiting SNr neuron activity. The standard model also suggests that SNr activity in the indirect pathway is controlled by MSNs disinhibiting the subthalamic nucleus (STN via the globus pallidus externa (GPe. Our model rather indicates that SNr activity is controlled by the direct GPe-SNr projections. This is partly because GPe strongly inhibits SNr but also due to depressing STN-SNr synapses. Furthermore, depressing GPe-SNr synapses allow the system to become sensitive to irregularly firing GPe subpopulations, as seen in dopamine depleted conditions, even when the GPe mean firing rate does not change. Similar to the direct pathway, simulations indicate that only a few percent of bursting indirect pathway MSNs can significantly increase the activity in SNr. Finally, the model predicts depressing STN-SNr synapses, since such an assumption explains experiments showing that a brief transient activation of the hyperdirect pathway generates a tri-phasic response in SNr, while a sustained STN activation has minor effects. This can be explained if STN-SNr synapses are depressing such that their effects are counteracted by the (known depressing GPe-SNr inputs.

  16. The bidirectionality of motor learning in the vestibulo-ocular reflex is a function of cerebellar mGluR1 receptors.

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    Titley, Heather K; Heskin-Sweezie, Raquel; Broussard, Dianne M

    2010-12-01

    Bidirectional changes in synaptic transmission have the potential to optimize the control of movement. However, it can be difficult to establish a causal relationship between the bidirectionality of synaptic plasticity and bidirectional changes in the speed of actual movements. We asked whether metabotropic glutamate receptor 1 (mGluR1) receptors, which participate in cerebellar long-term depression (LTD), are necessary for bidirectional motor learning in the vestibulo-ocular reflex (VOR). Cerebellar LTD and long-term potentiation (LTP) are thought to cause increases and decreases, respectively, in the gain of the VOR; the direction of learning depends on the behavioral protocol. We injected either the mGluR1 agonist (S)-DHPG or the antagonist YM 298198 bilaterally into the flocculus of alert cats, and then induced motor learning. In the presence of YM 298198, the VOR gain decreased in gain-up, as well as in gain-down protocols. (S)-DHPG augmented gain-up learning. Gain-down learning was not significantly affected by either drug. These results supported the hypothesis that gain-up learning relies on cerebellar LTD, but gain-down learning relies on a different mechanism. In the absence of mGluR1 activity, cerebellar LTD may be replaced with LTP, permitting learning in only one direction.

  17. ESP-102, a Combined Herbal Extract of Angelica gigas, Saururus chinensis, and Schisandra chinensis, Changes Synaptic Plasticity and Attenuates Scopolamine-Induced Memory Impairment in Rat Hippocampus Tissue

    Science.gov (United States)

    Kim, Hyun-Bum; Hwang, Eun-Sang; Choi, Ga-Young; Lee, Seok; Park, Tae-Suk; Lee, Cheol-Won; Lee, Eun-Suk; Kim, Young-Choong; Kim, Sang Seong; Lee, Sung-Ok; Park, Ji-Ho

    2016-01-01

    ESP-102, an extract from Angelica gigas, Saururus chinensis, and Schisandra chinensis, has been used as herbal medicine and dietary supplement in Korea. Despite the numerous bioactivities in vitro and in vivo studies, its effects on neuronal networks remain elusive. To address the neuronal effect, we examined synaptic plasticity in organotypic hippocampal slice culture with multielectrode array. Our results showed an increase in excitatory postsynaptic potential (EPSP), indicating the induction of long-term potentiation (LTP), in the presence of ESP-102. In addition, the neuroprotective effect of ESP-102 was also tested by application of scopolamine to the hippocampal slice. Interestingly, ESP-102 competitively antagonized the preventative LTP effect induced by scopolamine. The scopolamine-induced reduction in brain-derived neurotrophic factor (BDNF) and GluR-2 expression was also rescued by ESP-102. In terms of mode of action, ESP-102 appears to act on the presynaptic region independent of AMPA/NMDA receptors. Based on these findings, ESP-102 can be suggested as a novel herbal ingredient with memory enhancing as well as neuroprotective effects. PMID:27298627

  18. ESP-102, a Combined Herbal Extract of Angelica gigas, Saururus chinensis, and Schisandra chinensis, Changes Synaptic Plasticity and Attenuates Scopolamine-Induced Memory Impairment in Rat Hippocampus Tissue

    Directory of Open Access Journals (Sweden)

    Hyun-Bum Kim

    2016-01-01

    Full Text Available ESP-102, an extract from Angelica gigas, Saururus chinensis, and Schisandra chinensis, has been used as herbal medicine and dietary supplement in Korea. Despite the numerous bioactivities in vitro and in vivo studies, its effects on neuronal networks remain elusive. To address the neuronal effect, we examined synaptic plasticity in organotypic hippocampal slice culture with multielectrode array. Our results showed an increase in excitatory postsynaptic potential (EPSP, indicating the induction of long-term potentiation (LTP, in the presence of ESP-102. In addition, the neuroprotective effect of ESP-102 was also tested by application of scopolamine to the hippocampal slice. Interestingly, ESP-102 competitively antagonized the preventative LTP effect induced by scopolamine. The scopolamine-induced reduction in brain-derived neurotrophic factor (BDNF and GluR-2 expression was also rescued by ESP-102. In terms of mode of action, ESP-102 appears to act on the presynaptic region independent of AMPA/NMDA receptors. Based on these findings, ESP-102 can be suggested as a novel herbal ingredient with memory enhancing as well as neuroprotective effects.

  19. Neonatal Treatment with a Pegylated Leptin Antagonist Induces Sexually Dimorphic Effects on Neurones and Glial Cells, and on Markers of Synaptic Plasticity in the Developing Rat Hippocampal Formation.

    Science.gov (United States)

    López-Gallardo, M; Antón-Fernández, A; Llorente, R; Mela, V; Llorente-Berzal, A; Prada, C; Viveros, M P

    2015-08-01

    The present study aimed to better understand the role of the neonatal leptin surge, which peaks on postnatal day (PND)9-10, on the development of the hippocampal formation. Accordingly, male and female rats were administered with a pegylated leptin antagonist on PND9 and the expression of neurones, glial cells and diverse markers of synaptic plasticity was then analysed by immunohistochemistry in the hippocampal formation. Antagonism of the actions of leptin at this specific postnatal stage altered the number of glial fibrillary acidic protein positive cells, and also affected type 1 cannabinoid receptors, synaptophysin and brain-derived neurotrophic factor (BDNF), with the latter effect being sexually dimorphic. The results indicate that the physiological leptin surge occurring around PND 9-10 is critical for hippocampal formation development and that the dynamics of leptin activity might be different in males and females. The data obtained also suggest that some but not all the previously reported effects of maternal deprivation on hippocampal formation development (which markedly reduces leptin levels at PND 9-10) might be mediated by leptin deficiency in these animals.

  20. 5-HT(2C) serotonin receptor blockade prevents tau protein hyperphosphorylation and corrects the defect in hippocampal synaptic plasticity caused by a combination of environmental stressors in mice.

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    Busceti, Carla Letizia; Di Pietro, Paola; Riozzi, Barbara; Traficante, Anna; Biagioni, Francesca; Nisticò, Robert; Fornai, Francesco; Battaglia, Giuseppe; Nicoletti, Ferdinando; Bruno, Valeria

    2015-09-01

    Exposure to multimodal sensory stressors is an everyday occurrence and sometimes becomes very intense, such as during rave parties or other recreational events. A growing body of evidence suggests that strong environmental stressors might cause neuronal dysfunction on their own in addition to their synergistic action with illicit drugs. Mice were exposed to a combination of physical and sensory stressors that are reminiscent of those encountered in a rave party. However, this is not a model of rave because it lacks the rewarding properties of rave. A 14-h exposure to environmental stressors caused an impairment of hippocampal long-term potentiation (LTP) and spatial memory, and an enhanced phosphorylation of tau protein in the CA1 and CA3 regions. These effects were transient and critically depended on the activation of 5-HT2C serotonin receptors, which are highly expressed in the CA1 region. Acute systemic injection of the selective 5-HT2C antagonist, RS-102,221 (2 mg/kg, i.p., 2 min prior the onset of stress), prevented tau hyperphosphorylation and also corrected the defects in hippocampal LTP and spatial memory. These findings suggest that passive exposure to a combination of physical and sensory stressors causes a reversible hippocampal dysfunction, which might compromise mechanisms of synaptic plasticity and spatial memory for a few days. Drugs that block 5-HT2C receptors might protect the hippocampus against the detrimental effect of environmental stressors. PMID:26145279

  1. Phospho-regulated Drosophila adducin is a determinant of synaptic plasticity in a complex with Dlg and PIP2 at the larval neuromuscular junction

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    Simon Ji Hau Wang

    2014-11-01

    Full Text Available Adducin is a ubiquitously expressed actin- and spectrin-binding protein involved in cytoskeleton organization, and is regulated through phosphorylation of the myristoylated alanine-rich C-terminal kinase (MARCKS-homology domain by protein kinase C (PKC. We have previously shown that the Drosophila adducin, Hu-li tai shao (Hts, plays a role in larval neuromuscular junction (NMJ growth. Here, we find that the predominant isoforms of Hts at the NMJ contain the MARCKS-homology domain, which is important for interactions with Discs large (Dlg and phosphatidylinositol 4,5-bisphosphate (PIP2. Through the use of Proximity Ligation Assay (PLA, we show that the adducin-like Hts isoforms are in complexes with Dlg and PIP2 at the NMJ. We provide evidence that Hts promotes the phosphorylation and delocalization of Dlg at the NMJ through regulation of the transcript distribution of the PAR-1 and CaMKII kinases in the muscle. We also show that Hts interactions with Dlg and PIP2 are impeded through phosphorylation of the MARCKS-homology domain. These results are further evidence that Hts is a signaling-responsive regulator of synaptic plasticity in Drosophila.

  2. Administration of the TrkB receptor agonist 7,8-dihydroxyflavone prevents traumatic stress-induced spatial memory deficits and changes in synaptic plasticity.

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    Sanz-García, Ancor; Knafo, Shira; Pereda-Pérez, Inmaculada; Esteban, José A; Venero, César; Armario, Antonio

    2016-09-01

    Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic situations and it is characterized by cognitive deficits that include impaired explicit memory. The neurobiological bases of such PTSD-associated memory alterations are yet to be elucidated and no satisfactory treatment for them exists. To address this issue, we first studied whether a single exposure of young adult rats (60 days) to immobilization on boards (IMO), a putative model of PTSD, produces long-term behavioral effects (2-8 days) similar to those found in PTSD patients. Subsequently, we investigated whether the administration of the TrkB agonist 7,8-dihydroxyflavone (DHF) 8 h after stress (therapeutic window) ameliorated the PTSD-like effect of IMO and the associated changes in synaptic plasticity. A single IMO exposure induced a spatial memory impairment similar to that found in other animal models of PTSD or in PTSD patients. IMO also increased spine density and long-term potentiation (LTP) in the CA3-CA1 pathway. Significantly, DHF reverted both spatial memory impairment and the increase in LTP, while it produced no effect in the controls. These data provide novel insights into the possible neurobiological substrate for explicit memory impairment in PTSD patients, supporting the idea that the activation of the BDNF/TrkB pathway fulfils a protective role after severe stress. Administration of DHF in the aftermath of a traumatic experience might be relevant to prevent its long-term consequences. © 2016 Wiley Periodicals, Inc. PMID:27068341

  3. Deficiency of prolyl oligopeptidase in mice disturbs synaptic plasticity and reduces anxiety-like behaviour, body weight, and brain volume.

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    Höfling, Corinna; Kulesskaya, Natalia; Jaako, Külli; Peltonen, Iida; Männistö, Pekka T; Nurmi, Antti; Vartiainen, Nina; Morawski, Markus; Zharkovsky, Alexander; Võikar, Vootele; Roßner, Steffen; García-Horsman, J Arturo

    2016-06-01

    Prolyl oligopeptidase (PREP) has been implicated in neurodegeneration and neuroinflammation and has been considered a drug target to enhance memory in dementia. However, the true physiological role of PREP is not yet understood. In this paper, we report the phenotyping of a mouse line where the PREP gene has been knocked out. This work indicates that the lack of PREP in mice causes reduced anxiety but also hyperactivity. The cortical volumes of PREP knockout mice were smaller than those of wild type littermates. Additionally, we found increased expression of diazepam binding inhibitor protein in the cortex and of the somatostatin receptor-2 in the hippocampus of PREP knockout mice. Furthermore, immunohistochemistry and tail suspension test revealed lack of response of PREP knockout mice to lipopolysaccharide insult. Further analysis revealed significantly increased levels of polysialylated-neural cell adhesion molecule in PREP deficient mice. These findings might be explained as possible alteration in brain plasticity caused by PREP deficiency, which in turn affect behaviour and brain development. PMID:26996375

  4. Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats.

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    Liu, Su; Liu, Yue-Peng; Huang, Zhi-Jiang; Zhang, Yan-Kai; Song, Angela A; Ma, Ping-Chuan; Song, Xue-Jun

    2015-12-01

    Treating neuropathic pain continues to be a major clinical challenge and underlying mechanisms of neuropathic pain remain elusive. We have recently demonstrated that Wnt signaling, which is important in developmental processes of the nervous systems, plays critical roles in the development of neuropathic pain through the β-catenin-dependent pathway in the spinal cord and the β-catenin-independent pathway in primary sensory neurons after nerve injury. Here, we report that Wnt signaling may contribute to neuropathic pain through the atypical Wnt/Ryk signaling pathway in rats. Sciatic nerve injury causes a rapid-onset and long-lasting expression of Wnt3a, Wnt5b, and Ryk receptors in primary sensory neurons, and dorsal horn neurons and astrocytes. Spinal blocking of the Wnt/Ryk receptor signaling inhibits the induction and persistence of neuropathic pain without affecting normal pain sensitivity and locomotor activity. Blocking activation of the Ryk receptor with anti-Ryk antibody, in vivo or in vitro, greatly suppresses nerve injury-induced increased intracellular Ca and hyperexcitability of the sensory neurons, and also the enhanced plasticity of synapses between afferent C-fibers and the dorsal horn neurons, and activation of the NR2B receptor and the subsequent Ca-dependent signals CaMKII, Src, ERK, PKCγ, and CREB in sensory neurons and the spinal cord. These findings indicate a critical mechanism underlying the pathogenesis of neuropathic pain and suggest that targeting the Wnt/Ryk signaling may be an effective approach for treating neuropathic pain.

  5. Plasticidade sináptica: natureza e cultura moldando o Self Synaptic plasticity: nature and nurture shaping the self

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    Angela Donato Oliva

    2009-01-01

    Full Text Available O cérebro em desenvolvimento segue inicialmente um plano genético, estabelecido pela história evolutiva da espécie humana, porém é muito sensível ao ambiente. Estímulos ambientais modificam a estrutura dos circuitos neurais, refinando e tornando as sinapses, alvo de ação dos neurotransmissores, mais eficientes por meio de atividade elétrica e mensageiros químicos. O objetivo desse estudo é discutir teoricamente como a plasticidade e a especificação prévia de sistemas cerebrais coexistem no cérebro. Conclui-se destacando a importância de integrar aspectos de aprendizagem social e da biologia na construção e refinamento das variadas habilidades humanas.The developing brain requires a genetic plan, established by the evolutionary history of human species, but it is also very sensitive to the surrounding environment. Environmental stimuli can modify the structure of neural circuits, refining and making synapses, which are the target of neurotransmitters, more efficient by electrical activity and chemical messengers. The aim of the present study is to discuss theoretically how both plasticity and previous specification of brain systems coexist in the brain. The conclusion shows the importance to integrate aspects of social learning and biology in building and refining the various humane skills.

  6. Enhanced Glutamatergic Synaptic Plasticity in the Hippocampal CA1 Field of Food-Restricted Rats: Involvement of CB1 Receptors.

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    Talani, Giuseppe; Licheri, Valentina; Biggio, Francesca; Locci, Valentina; Mostallino, Maria Cristina; Secci, Pietro Paolo; Melis, Valentina; Dazzi, Laura; Carta, Gianfranca; Banni, Sebastiano; Biggio, Giovanni; Sanna, Enrico

    2016-04-01

    The endogenous endocannabinoid system has a crucial role in regulating appetite and feeding behavior in mammals, as well as working memory and reward mechanisms. In order to elucidate the possible role of cannabinoid type-1 receptors (CB1Rs) in the regulation of hippocampal plasticity in animals exposed to food restriction (FR), we limited the availability of food to a 2-h daily period for 3 weeks in Sprague-Dawley rats. FR rats showed a higher long-term potentiation at hippocampal CA1 excitatory synapses with a parallel increase in glutamate release when compared with animals fed ad libitum. FR rats showed a significant increase in the long-term spatial memory determined by Barnes maze. FR was also associated with a decreased inhibitory effect of the CB1R agonist win55,212-2 on glutamatergic field excitatory postsynaptic potentials, together with a decrease in hippocampal CB1R protein expression. In addition, hippocampal brain-derived neurotrophic factor protein levels and mushroom dendritic spine density were significantly enhanced in FR rats. Altogether, our data suggest that alterations of hippocampal CB1R expression and function in FR rats are associated with dendritic spine remodeling and functional potentiation of CA1 excitatory synapses, and these findings are consistent with increasing evidence supporting the idea that FR may improve cognitive functions.

  7. Neuromodulation and Synaptic Plasticity for the Control of Fast Periodic Movement:Energy Efficiency in Coupled Compliant Joints via PCA

    Directory of Open Access Journals (Sweden)

    Philipp eStratmann

    2016-03-01

    Full Text Available There are multiple indications that the nervous system of animals tunes muscle output to exploit natural dynamics of the elastic locomotor system and the environment. This is an advantageous strategy especially in fast periodic movements, since the elastic elements store energy and increase energy efficiency and movement speed.Experimental evidence suggests that coordination among joints involves proprioceptive input and neuromodulatory influence originating in the brain stem. However, the neural strategies underlying the coordination of fast periodic movements remain poorly understood.Based on robotics control theory, we suggest that the nervous system implements a mechanism to accomplish coordination between joints by a linear coordinate transformation from the multi-dimensional space representing proprioceptive input at the joint level into a one-dimensional controller space. In this one-dimensional subspace, the movements of a whole limb can be driven by a single oscillating unit as simple as a reflex interneuron. The output of the oscillating unit is transformed back to joint space via the same transformation. The transformation weights correspond to the dominant principal component of the movement.In this study, we propose a biologically plausible neural network to exemplify that the central nervous system may encode our controller design. Using theoretical considerations and computer simulations, we demonstrate that spike-timing-dependent plasticity for the input mapping and serotonergic neuromodulation for the output mapping can extract the dominant principal component of sensory signals. Our simulations show that our network can reliably control mechanical systems of different complexity and increase the energy efficiency of ongoing cyclic movements.The proposed network is simple and consistent with previous biologic experiments. Thus, our controller could serve as a candidate to describe the neural control of fast, energy

  8. Neuromodulation and Synaptic Plasticity for the Control of Fast Periodic Movement: Energy Efficiency in Coupled Compliant Joints via PCA

    Science.gov (United States)

    Stratmann, Philipp; Lakatos, Dominic; Albu-Schäffer, Alin

    2016-01-01

    There are multiple indications that the nervous system of animals tunes muscle output to exploit natural dynamics of the elastic locomotor system and the environment. This is an advantageous strategy especially in fast periodic movements, since the elastic elements store energy and increase energy efficiency and movement speed. Experimental evidence suggests that coordination among joints involves proprioceptive input and neuromodulatory influence originating in the brain stem. However, the neural strategies underlying the coordination of fast periodic movements remain poorly understood. Based on robotics control theory, we suggest that the nervous system implements a mechanism to accomplish coordination between joints by a linear coordinate transformation from the multi-dimensional space representing proprioceptive input at the joint level into a one-dimensional controller space. In this one-dimensional subspace, the movements of a whole limb can be driven by a single oscillating unit as simple as a reflex interneuron. The output of the oscillating unit is transformed back to joint space via the same transformation. The transformation weights correspond to the dominant principal component of the movement. In this study, we propose a biologically plausible neural network to exemplify that the central nervous system (CNS) may encode our controller design. Using theoretical considerations and computer simulations, we demonstrate that spike-timing-dependent plasticity (STDP) for the input mapping and serotonergic neuromodulation for the output mapping can extract the dominant principal component of sensory signals. Our simulations show that our network can reliably control mechanical systems of different complexity and increase the energy efficiency of ongoing cyclic movements. The proposed network is simple and consistent with previous biologic experiments. Thus, our controller could serve as a candidate to describe the neural control of fast, energy

  9. Neuromodulation and Synaptic Plasticity for the Control of Fast Periodic Movement: Energy Efficiency in Coupled Compliant Joints via PCA.

    Science.gov (United States)

    Stratmann, Philipp; Lakatos, Dominic; Albu-Schäffer, Alin

    2016-01-01

    There are multiple indications that the nervous system of animals tunes muscle output to exploit natural dynamics of the elastic locomotor system and the environment. This is an advantageous strategy especially in fast periodic movements, since the elastic elements store energy and increase energy efficiency and movement speed. Experimental evidence suggests that coordination among joints involves proprioceptive input and neuromodulatory influence originating in the brain stem. However, the neural strategies underlying the coordination of fast periodic movements remain poorly understood. Based on robotics control theory, we suggest that the nervous system implements a mechanism to accomplish coordination between joints by a linear coordinate transformation from the multi-dimensional space representing proprioceptive input at the joint level into a one-dimensional controller space. In this one-dimensional subspace, the movements of a whole limb can be driven by a single oscillating unit as simple as a reflex interneuron. The output of the oscillating unit is transformed back to joint space via the same transformation. The transformation weights correspond to the dominant principal component of the movement. In this study, we propose a biologically plausible neural network to exemplify that the central nervous system (CNS) may encode our controller design. Using theoretical considerations and computer simulations, we demonstrate that spike-timing-dependent plasticity (STDP) for the input mapping and serotonergic neuromodulation for the output mapping can extract the dominant principal component of sensory signals. Our simulations show that our network can reliably control mechanical systems of different complexity and increase the energy efficiency of ongoing cyclic movements. The proposed network is simple and consistent with previous biologic experiments. Thus, our controller could serve as a candidate to describe the neural control of fast, energy

  10. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  11. REM Sleep-Dependent Bidirectional Regulation of Hippocampal-Based Emotional Memory and LTP.

    Science.gov (United States)

    Ravassard, Pascal; Hamieh, Al Mahdy; Joseph, Mickaël Antoine; Fraize, Nicolas; Libourel, Paul-Antoine; Lebarillier, Léa; Arthaud, Sébastien; Meissirel, Claire; Touret, Monique; Malleret, Gaël; Salin, Paul-Antoine

    2016-04-01

    Prolonged rapid-eye-movement (REM) sleep deprivation has long been used to study the role of REM sleep in learning and memory processes. However, this method potentially induces stress and fatigue that may directly affect cognitive functions. Here, by using a short-term and nonstressful REM sleep deprivation (RSD) method we assessed in rats the bidirectional influence of reduced and increased REM sleep amount on hippocampal-dependent emotional memory and plasticity. Our results indicate that 4 h RSD impaired consolidation of contextual fear conditioning (CFC) and induction of long-term potentiation (LTP), while decreasing density of Egr1/Zif268-expressing neurons in the CA1 region of the dorsal hippocampus. LTP and Egr1 expression were not affected in ventral CA1. Conversely, an increase in REM sleep restores and further facilitates CFC consolidation and LTP induction, and also increases Egr1 expression in dorsal CA1. Moreover, CFC consolidation, Egr1 neuron density, and LTP amplitude in dorsal CA1 show a positive correlation with REM sleep amount. Altogether, these results indicate that mild changes in REM sleep amount bidirectionally affect memory and synaptic plasticity mechanisms occurring in the CA1 area of the dorsal hippocampus.

  12. Molecular Recognition within Synaptic Scaffolds

    DEFF Research Database (Denmark)

    Erlendsson, Simon

    domains, responsible for tethering their respective synaptic protein ligands. Therefore, understanding the specificity and binding mechanisms of PDZ domain proteins is essential to understand regulation of synaptic plasticity. PICK1 is a PDZ domain-containing scaffolding protein predominantly expressed...... and characterized in the postsynaptic neurons, where it is involved in regulating processes underlying LTP and LTD. However, PICK1 has also been found to interact with a wide range of other regulatory proteins, receptors and transporters, which implicates PICK1 in several processes important for proper synaptic...

  13. Long lasting protein synthesis- and activity-dependent spine shrinkage and elimination after synaptic depression.

    Directory of Open Access Journals (Sweden)

    Yazmín Ramiro-Cortés

    Full Text Available Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD mediated by metabotropic glutamate receptors (mGluRs through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation.

  14. Synaptic encoding of temporal contiguity

    Directory of Open Access Journals (Sweden)

    Srdjan eOstojic

    2013-04-01

    Full Text Available Often we need to perform tasks in an environment that changes stochastically. In these situations it is important to learn the statistics of sequences of events in order to predict the future and the outcome of our actions. The statistical description of many of these sequences can be reduced to the set of probabilities that a particular event follows another event (temporal contiguity. Under these conditions, it is important to encode and store in our memory these transition probabilities. Here we show that for a large class of synaptic plasticity models, the distribution of synaptic strengths encodes transitions probabilities. Specifically, when the synaptic dynamics depend on pairs of contiguous events and the synapses can remember multiple instances of the transitions, then the average synaptic weights are a monotonic function of the transition probabilities. The synaptic weights converge to the distribution encoding the probabilities also when the correlations between consecutive synaptic modifications are considered. We studied how this distribution depends on the number of synaptic states for a specific model of a multi-state synapse with hard bounds. In the case of bistable synapses, the average synaptic weights are a smooth function of the transition probabilities and the accuracy of the encoding depends on the learning rate. As the number of synaptic states increases, the average synaptic weights become a step function of the transition probabilities. We finally show that the information stored in the synaptic weights can be read out by a simple rate-based neural network. Our study shows that synapses encode transition probabilities under general assumptions and this indicates that temporal contiguity is likely to be encoded and harnessed in almost every neural circuit in the brain.

  15. Regulation of synaptic connectivity by glia

    OpenAIRE

    Eroglu, Cagla; Barres, Ben A

    2010-01-01

    The human brain contains more than 100 trillion (1014) synaptic connections, which form all of its neural circuits. Neuroscientists have long been interested in how this complex synaptic web is weaved during development and remodelled during learning and disease. Recent studies have uncovered that glial cells are important regulators of synaptic connectivity. These cells are far more active than was previously thought and are powerful controllers of synapse formation, function, plasticity and...

  16. Neuroprotective effect of β-asarone against Alzheimer’s disease: regulation of synaptic plasticity by increased expression of SYP and GluR1

    Directory of Open Access Journals (Sweden)

    Liu SJ

    2016-04-01

    cells was detected by Western blot assay in the hippocampus and brain cortex tissues of mice.Results: β-asarone at a high dose reduced escape latency and upregulated SYP and GluR1 expression at both medium and high doses. Cell morphology evaluation showed that β-asarone treatment did not result in obvious cell surface spots and cytoplasmic granularity. β-asarone had a dose-dependent effect on cell proliferation.Conclusion: β-asarone antagonized the Aβ neurotoxicity in vivo, improved the learning and memory ability of APP/PS1 mice, and increased the expression of SYP and GluR1 both in vivo and in vitro. Thus, β-asarone may be a potential drug for the treatment of Alzheimer’s disease.Keywords: neuroprotective effect, β-asarone, synaptic plasticity, synaptophysin, glutamatergic receptor 1

  17. Bidirectional optical scattering facility

    Data.gov (United States)

    Federal Laboratory Consortium — Goniometric optical scatter instrument (GOSI) The bidirectional reflectance distribution function (BRDF) quantifies the angular distribution of light scattered from...

  18. Differential alterations of synaptic plasticity in dentate gyrus and CA1 hippocampal area of Calbindin-D28K knockout mice

    NARCIS (Netherlands)

    Westerink, R.H.S.; Beekwilder, J.P.; Wadman, W.J.

    2012-01-01

    Regulation of the intracellular calcium concentration ([Ca(2+)](i)) is of critical importance for synaptic function. Therefore, neurons buffer [Ca(2+)](i) using intracellular Ca(2+)-binding proteins (CaBPs). Previous evidence suggests that Calbindin-D(28K) (CB), an abundantly expressed endogenous fa

  19. Synchronization stability and firing transitions in two types of class I neuronal networks with short-term plasticity.

    Science.gov (United States)

    Zhang, Honghui; Wang, Qingyun; He, Xiaoyan; Chen, Guanrong

    2014-01-01

    This paper investigates synchronization stability and firing transition in two types of the modified canonical class I neuronal networks, where the short-term plasticity of synapse is introduced. We mainly consider both unidirectional chain and global coupling configurations. Previous studies have shown that the coupled class I neurons can spontaneously de-synchronize. Presently, the short-term plasticity of synapse is considered to check the universality of this phenomenon. Based on the theoretical analysis and numerical simulation, it is shown that unidirectionally chain coupled class I neurons can realize synchronization, whereas bidirectionally coupled chain neurons cannot synchronize, and globally coupled class I neurons de-synchronize. Furthermore, the dynamics of coupled neurons with different firing modes are also studied in numerical simulations, and interesting transitions of different firing modes can be induced by the short-term plasticity. The obtained results can be helpful to further understand important effects of the short-term synaptic plasticity on realistic neuronal systems.

  20. The role of microglia in synaptic stripping and synaptic degeneration: a revised perspective

    OpenAIRE

    Perry, V. Hugh; O'Connor, Vincent

    2010-01-01

    Chronic neurodegenerative diseases of the CNS (central nervous system) are characterized by the loss of neurons. There is, however, growing evidence to show that an early stage of this process involves degeneration of presynaptic terminals prior to the loss of the cell body. Synaptic plasticity in CNS pathology has been associated with microglia and the phenomenon of synaptic stripping. We review here the evidence for the involvement of microglia in synaptic stripping and synapse degeneration...

  1. The effect of acute swim stress and training in the water maze on hippocampal synaptic activity as well as plasticity in the dentate gyrus of freely moving rats: revisiting swim-induced LTP reinforcement.

    Science.gov (United States)

    Tabassum, Heena; Frey, Julietta U

    2013-12-01

    Hippocampal long-term potentiation (LTP) is a cellular model of learning and memory. An early form of LTP (E-LTP) can be reinforced into its late form (L-LTP) by various behavioral interactions within a specific time window ("behavioral LTP-reinforcement"). Depending on the type and procedure used, various studies have shown that stress differentially affects synaptic plasticity. Under low stress, such as novelty detection or mild foot shocks, E-LTP can be transformed into L-LTP in the rat dentate gyrus (DG). A reinforcing effect of a 2-min swim, however, has only been shown in (Korz and Frey (2003) J Neurosci 23:7281-7287; Korz and Frey (2005) J Neurosci 25:7393-7400; Ahmed et al. (2006) J Neurosci 26:3951-3958; Sajikumar et al., (2007) J Physiol 584.2:389-400) so far. We have reinvestigated these studies using the same as well as an improved recording technique which allowed the recording of field excitatory postsynaptic potentials (fEPSP) and the population spike amplitude (PSA) at their places of generation in freely moving rats. We show that acute swim stress led to a long-term depression (LTD) in baseline values of PSA and partially fEPSP. In contrast to earlier studies a LTP-reinforcement by swimming could never be reproduced. Our results indicate that 2-min swim stress influenced synaptic potentials as well as E-LTP negatively.

  2. AMPA receptor inhibition by synaptically released zinc.

    Science.gov (United States)

    Kalappa, Bopanna I; Anderson, Charles T; Goldberg, Jacob M; Lippard, Stephen J; Tzounopoulos, Thanos

    2015-12-22

    The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.

  3. Synaptic determinants of Rett syndrome

    Directory of Open Access Journals (Sweden)

    Elena M B Boggio

    2010-08-01

    Full Text Available There is mounting evidence showing that the structural and molecular organization of synaptic connections are affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synapsopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett Syndrome (RS. RS (MIM312750 is an X-linked dominant neurological disorder that is caused, in the majority of cases by mutations in methyl-CpG-binding protein 2 (MeCP2. This review will focus on the current knowledge of the synaptic alterations produced by mutations of the gene MeCP2 in mouse models of RS and will highlight prospects experimental therapies currently in use. Different experimental approaches have revealed that RS could be the consequence of an impairment in the homeostasis of synaptic transmission in specific brain regions. Indeed, several forms of experience-induced neuronal plasticity are impaired in the absence of MeCP2. Based on the results presented in this review, it is reasonable to propose that understanding how the brain is affected by diseases such as RS is at reach. This effort will bring us closer to identify the neurobiological bases of human cognition.

  4. Sleep, plasticity and memory from molecules to whole-brain networks.

    Science.gov (United States)

    Abel, Ted; Havekes, Robbert; Saletin, Jared M; Walker, Matthew P

    2013-09-01

    Despite the ubiquity of sleep across phylogeny, its function remains elusive. In this review, we consider one compelling candidate: brain plasticity associated with memory processing. Focusing largely on hippocampus-dependent memory in rodents and humans, we describe molecular, cellular, network, whole-brain and behavioral evidence establishing a role for sleep both in preparation for initial memory encoding, and in the subsequent offline consolidation of memory. Sleep and sleep deprivation bidirectionally alter molecular signaling pathways that regulate synaptic strength and control plasticity-related gene transcription and protein translation. At the cellular level, sleep deprivation impairs cellular excitability necessary for inducing synaptic potentiation and accelerates the decay of long-lasting forms of synaptic plasticity. In contrast, rapid eye movement (REM) and non-rapid eye movement (NREM) sleep enhance previously induced synaptic potentiation, although synaptic de-potentiation during sleep has also been observed. Beyond single cell dynamics, large-scale cell ensembles express coordinated replay of prior learning-related firing patterns during subsequent NREM sleep. At the whole-brain level, somewhat analogous learning-associated hippocampal (re)activation during NREM sleep has been reported in humans. Moreover, the same cortical NREM oscillations associated with replay in rodents also promote human hippocampal memory consolidation, and this process can be manipulated using exogenous reactivation cues during sleep. Mirroring molecular findings in rodents, specific NREM sleep oscillations before encoding refresh human hippocampal learning capacity, while deprivation of sleep conversely impairs subsequent hippocampal activity and associated encoding. Together, these cross-descriptive level findings demonstrate that the unique neurobiology of sleep exerts powerful effects on molecular, cellular and network mechanisms of plasticity that govern both initial

  5. Bidirectional coherent classical communication

    OpenAIRE

    Harrow, Aram W.; Leung, Debbie W.

    2005-01-01

    A unitary interaction coupling two parties enables quantum or classical communication in both the forward and backward directions. Each communication capacity can be thought of as a tradeoff between the achievable rates of specific types of forward and backward communication. Our first result shows that for any bipartite unitary gate, bidirectional coherent classical communication is no more difficult than bidirectional classical communication — they have the same achievable rate regions. ...

  6. Effect of castration on the susceptibility of male rats to the sleep deprivation-induced impairment of behavioral and synaptic plasticity.

    Science.gov (United States)

    Hajali, Vahid; Sheibani, Vahid; Ghazvini, Hamed; Ghadiri, Tahereh; Valizadeh, Toktam; Saadati, Hakimeh; Shabani, Mohammad

    2015-09-01

    In both human and animal studies, the effect of sleep deficiency on cognitive performances has mostly been studied during adulthood in males, but very little data exist concerning the effects of poor sleep in gonadal hormones-depleted status, such as aging or gonadectomized (GDX) male animal models. The present study investigated the potential modulatory effects of the endogenous male sex hormones on the 48h REM sleep deprivation (SD)-induced cognitive and synaptic impairments by comparing the gonadally intact with castrated male rats, a rodent model of androgen-deprived male animals. The multiple platform method was used for inducing REM-SD and spatial performances were evaluated using Morris water maze (MWM) task. Early long-term potentiation (E-LTP) was measured in area CA1 of the hippocampus and PCR and western blotting assays were employed to assess brain derived neurotrophic factor (BDNF) gene and protein expression in the hippocampus. To reveal any influence of sleep loss on stress level, we also evaluated the plasma corticosterone levels of animals. Regardless of reproductive status, REM-SD significantly disrupted short-term memory and LTP, as well as hippocampal BDNF expression. The corticosterone levels were not significantly changed following REM-SD neither in intact nor in GDX male rats. These findings suggest that depletion of male sex steroid hormones by castration does not lead to any heightened sensitivity of male animals to the deleterious effects of 48h REM-SD on cognitive and synaptic performances.

  7. Ionising Radiation Immediately Impairs Synaptic Plasticity-Associated Cytoskeletal Signalling Pathways in HT22 Cells and in Mouse Brain: An In Vitro/In Vivo Comparison Study

    Science.gov (United States)

    Kempf, Stefan J.; Buratovic, Sonja; von Toerne, Christine; Moertl, Simone; Stenerlöw, Bo; Hauck, Stefanie M.; Atkinson, Michael J.; Eriksson, Per; Tapio, Soile

    2014-01-01

    Patients suffering from brain malignancies are treated with high-dose ionising radiation. However, this may lead to severe learning and memory impairment. Preventive treatments to minimise these side effects have not been possible due to the lack of knowledge of the involved signalling pathways and molecular targets. Mouse hippocampal neuronal HT22 cells were irradiated with acute gamma doses of 0.5 Gy, 1.0 Gy and 4.0 Gy. Changes in the cellular proteome were investigated by isotope-coded protein label technology and tandem mass spectrometry after 4 and 24 hours. To compare the findings with the in vivo response, male NMRI mice were irradiated on postnatal day 10 with a gamma dose of 1.0 Gy, followed by evaluation of the cellular proteome of hippocampus and cortex 24 hours post-irradiation. Analysis of the in vitro proteome showed that signalling pathways related to synaptic actin-remodelling were significantly affected at 1.0 Gy and 4.0 Gy but not at 0.5 Gy after 4 and 24 hours. We observed radiation-induced reduction of the miR-132 and Rac1 levels; miR-132 is known to regulate Rac1 activity by blocking the GTPase-activating protein p250GAP. In the irradiated hippocampus and cortex we observed alterations in the signalling pathways similar to those in vitro. The decreased expression of miR-132 and Rac1 was associated with an increase in hippocampal cofilin and phospho-cofilin. The Rac1-Cofilin pathway is involved in the modulation of synaptic actin filament formation that is necessary for correct spine and synapse morphology to enable processes of learning and memory. We suggest that acute radiation exposure leads to rapid dendritic spine and synapse morphology alterations via aberrant cytoskeletal signalling and processing and that this is associated with the immediate neurocognitive side effects observed in patients treated with ionising radiation. PMID:25329592

  8. Ionising radiation immediately impairs synaptic plasticity-associated cytoskeletal signalling pathways in HT22 cells and in mouse brain: an in vitro/in vivo comparison study.

    Directory of Open Access Journals (Sweden)

    Stefan J Kempf

    Full Text Available Patients suffering from brain malignancies are treated with high-dose ionising radiation. However, this may lead to severe learning and memory impairment. Preventive treatments to minimise these side effects have not been possible due to the lack of knowledge of the involved signalling pathways and molecular targets. Mouse hippocampal neuronal HT22 cells were irradiated with acute gamma doses of 0.5 Gy, 1.0 Gy and 4.0 Gy. Changes in the cellular proteome were investigated by isotope-coded protein label technology and tandem mass spectrometry after 4 and 24 hours. To compare the findings with the in vivo response, male NMRI mice were irradiated on postnatal day 10 with a gamma dose of 1.0 Gy, followed by evaluation of the cellular proteome of hippocampus and cortex 24 hours post-irradiation. Analysis of the in vitro proteome showed that signalling pathways related to synaptic actin-remodelling were significantly affected at 1.0 Gy and 4.0 Gy but not at 0.5 Gy after 4 and 24 hours. We observed radiation-induced reduction of the miR-132 and Rac1 levels; miR-132 is known to regulate Rac1 activity by blocking the GTPase-activating protein p250GAP. In the irradiated hippocampus and cortex we observed alterations in the signalling pathways similar to those in vitro. The decreased expression of miR-132 and Rac1 was associated with an increase in hippocampal cofilin and phospho-cofilin. The Rac1-Cofilin pathway is involved in the modulation of synaptic actin filament formation that is necessary for correct spine and synapse morphology to enable processes of learning and memory. We suggest that acute radiation exposure leads to rapid dendritic spine and synapse morphology alterations via aberrant cytoskeletal signalling and processing and that this is associated with the immediate neurocognitive side effects observed in patients treated with ionising radiation.

  9. GluN2B-containing NMDA receptors contribute to the beneficial effects of hydrogen sulfide on cognitive and synaptic plasticity deficits in APP/PS1 transgenic mice.

    Science.gov (United States)

    Yang, Yuan-Jian; Zhao, Ying; Yu, Bin; Xu, Guo-Gang; Wang, Wei; Zhan, Jin-Qiong; Tang, Zhen-Yu; Wang, Ting; Wei, Bo

    2016-10-29

    Alzheimer's disease (AD) is the most common type of clinical dementia. Previous studies have demonstrated that hydrogen sulfide (H2S) is implicated with the pathology of AD, and exogenous H2S attenuates spatial memory impairments in AD animal models. However, the molecular mechanism by which H2S improves cognition in AD has not been fully explored. Here, we report that chronic administration of sodium hydrosulfide (NaHS, a H2S donor) elevated hippocampal H2S levels and enhanced hippocampus-dependent contextual fear memory and novel object recognition in amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice. In parallel with these behavioral results, treating transgenic mice with NaHS reversed impaired hippocampal long-term potentiation (LTP), which is deemed as the neurobiological basis of learning and memory. At the molecular level, we found that treatment with NaHS did not affect the expression of the GluN1 and GluN2A subunits of NMDA receptor (NMDAR), but did prevent the downregulation of GluN2B subunit and restored its synaptic abundance, response and downstream signaling in the hippocampus in transgenic mice. Moreover, applying Ro 25-6981, a specific GluN2B antagonist, abolished the beneficial effects of NaHS on cognitive performance and hippocampal LTP in transgenic mice. Collectively, our results indicate that H2S can reverse cognitive and synaptic plasticity deficits in AD model mice by restoring surface GluN2B expression and the function of GluN2B-containing NMDARs.

  10. EDITORIAL: Synaptic electronics Synaptic electronics

    Science.gov (United States)

    Demming, Anna; Gimzewski, James K.; Vuillaume, Dominique

    2013-09-01

    Conventional computers excel in logic and accurate scientific calculations but make hard work of open ended problems that human brains handle easily. Even von Neumann—the mathematician and polymath who first developed the programming architecture that forms the basis of today's computers—was already looking to the brain for future developments before his death in 1957 [1]. Neuromorphic computing uses approaches that better mimic the working of the human brain. Recent developments in nanotechnology are now providing structures with very accommodating properties for neuromorphic approaches. This special issue, with guest editors James K Gimzewski and Dominique Vuillaume, is devoted to research at the serendipitous interface between the two disciplines. 'Synaptic electronics', looks at artificial devices with connections that demonstrate behaviour similar to synapses in the nervous system allowing a new and more powerful approach to computing. Synapses and connecting neurons respond differently to incident signals depending on the history of signals previously experienced, ultimately leading to short term and long term memory behaviour. The basic characteristics of a synapse can be replicated with around ten simple transistors. However with the human brain having around 1011 neurons and 1015 synapses, artificial neurons and synapses from basic transistors are unlikely to accommodate the scalability required. The discovery of nanoscale elements that function as 'memristors' has provided a key tool for the implementation of synaptic connections [2]. Leon Chua first developed the concept of the 'The memristor—the missing circuit element' in 1971 [3]. In this special issue he presents a tutorial describing how memristor research has fed into our understanding of synaptic behaviour and how they can be applied in information processing [4]. He also describes, 'The new principle of local activity, which uncovers a minuscule life-enabling "Goldilocks zone", dubbed the

  11. Flexible Proton-Gated Oxide Synaptic Transistors on Si Membrane.

    Science.gov (United States)

    Zhu, Li Qiang; Wan, Chang Jin; Gao, Ping Qi; Liu, Yang Hui; Xiao, Hui; Ye, Ji Chun; Wan, Qing

    2016-08-24

    Ion-conducting materials have received considerable attention for their applications in fuel cells, electrochemical devices, and sensors. Here, flexible indium zinc oxide (InZnO) synaptic transistors with multiple presynaptic inputs gated by proton-conducting phosphorosilicate glass-based electrolyte films are fabricated on ultrathin Si membranes. Transient characteristics of the proton gated InZnO synaptic transistors are investigated, indicating stable proton-gating behaviors. Short-term synaptic plasticities are mimicked on the proposed proton-gated synaptic transistors. Furthermore, synaptic integration regulations are mimicked on the proposed synaptic transistor networks. Spiking logic modulations are realized based on the transition between superlinear and sublinear synaptic integration. The multigates coupled flexible proton-gated oxide synaptic transistors may be interesting for neuroinspired platforms with sophisticated spatiotemporal information processing. PMID:27471861

  12. Learning and reconsolidation implicate different synaptic mechanisms.

    Science.gov (United States)

    Li, Yan; Meloni, Edward G; Carlezon, William A; Milad, Mohammed R; Pitman, Roger K; Nader, Karim; Bolshakov, Vadim Y

    2013-03-19

    Synaptic mechanisms underlying memory reconsolidation after retrieval are largely unknown. Here we report that synapses in projections to the lateral nucleus of the amygdala implicated in auditory fear conditioning, which are potentiated by learning, enter a labile state after memory reactivation, and must be restabilized through a postsynaptic mechanism implicating the mammalian target of rapamycin kinase-dependent signaling. Fear-conditioning-induced synaptic enhancements were primarily presynaptic in origin. Reconsolidation blockade with rapamycin, inhibiting mammalian target of rapamycin kinase activity, suppressed synaptic potentiation in slices from fear-conditioned rats. Surprisingly, this reduction of synaptic efficacy was mediated by post- but not presynaptic mechanisms. These findings suggest that different plasticity rules may apply to the processes underlying the acquisition of original fear memory and postreactivational stabilization of fear-conditioning-induced synaptic enhancements mediating fear memory reconsolidation. PMID:23487762

  13. Spike-timing dependent plasticity and the cognitive map

    Directory of Open Access Journals (Sweden)

    Daniel eBush

    2010-10-01

    Full Text Available Since the discovery of place cells – single pyramidal neurons that encode spatial location – it has been hypothesised that the hippocampus may act as a cognitive map of known environments. This putative function has been extensively modelled using auto-associative networks, which utilise rate-coded synaptic plasticity rules in order to generate strong bi-directional connections between concurrently active place cells that encode for neighbouring place fields. However, empirical studies using hippocampal cultures have demonstrated that the magnitude and direction of changes in synaptic strength can also be dictated by the relative timing of pre- and post- synaptic firing according to a spike-timing dependent plasticity (STDP rule. Furthermore, electrophysiology studies have identified persistent ‘theta-coded’ temporal correlations in place cell activity in vivo, characterised by phase precession of firing as the corresponding place field is traversed. It is not yet clear if STDP and theta-coded neural dynamics are compatible with cognitive map theory and previous rate-coded models of spatial learning in the hippocampus. Here, we demonstrate that an STDP rule based on empirical data obtained from the hippocampus can mediate rate-coded Hebbian learning when pre- and post- synaptic activity is stochastic and has no persistent sequence bias. We subsequently demonstrate that a spiking recurrent neural network that utilises this STDP rule, alongside theta-coded neural activity, allows the rapid development of a cognitive map during directed or random exploration of an environment of overlapping place fields. Hence, we establish that STDP and phase precession are compatible with rate-coded models of cognitive map development.

  14. Bidirectional grating compressors

    Science.gov (United States)

    Wang, Cheng; Li, Zhaoyang; Li, Shuai; Liu, Yanqi; Leng, Yuxin; Li, Ruxin

    2016-07-01

    A bidirectional grating compressor for chirped pulse amplifiers is presented. It compresses a laser beam simultaneously in two opposite directions. The pulse compressor is shown to promote chirped pulse amplifiers' output energy without grating damages. To verify the practicability, an experiment is carried out. In addition, a crosscorrelation instrument is designed and set up to test the time synchronization between these two femtosecond pulses.

  15. Restoration of synaptic function in sight for degenerative retinal disease

    OpenAIRE

    Schubert, Timm; Wissinger, Bernd

    2015-01-01

    Synaptic disorganization is a prominent feature of many neurological diseases of the CNS, including Parkinson’s disease, intellectual development disorders, and autism. Although synaptic plasticity is critical for learning and memory, it is unclear whether this innate property helps restore synaptic function in disease once the primary cause of disease is abrogated. An answer to this question may come from a recent investigation in X-linked retinoschisis, a currently untreatable retinopathy. ...

  16. Synaptic Tagging, Evaluation of Memories, and the Distal Reward Problem

    Science.gov (United States)

    Papper, Marc; Kempter, Richard; Leibold, Christian

    2011-01-01

    Long-term synaptic plasticity exhibits distinct phases. The synaptic tagging hypothesis suggests an early phase in which synapses are prepared, or "tagged," for protein capture, and a late phase in which those proteins are integrated into the synapses to achieve memory consolidation. The synapse specificity of the tags is consistent with…

  17. D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signalling to control synaptic plasticity and cocaine-induced responses.

    Science.gov (United States)

    Cahill, E; Pascoli, V; Trifilieff, P; Savoldi, D; Kappès, V; Lüscher, C; Caboche, J; Vanhoutte, P

    2014-12-01

    Convergent dopamine and glutamate signalling onto the extracellular signal-regulated kinase (ERK) pathway in medium spiny neurons (MSNs) of the striatum controls psychostimulant-initiated adaptive processes underlying long-lasting behavioural changes. We hypothesised that the physical proximity of dopamine D1 (D1R) and glutamate NMDA (NMDAR) receptors, achieved through the formation of D1R/NMDAR complexes, may act as a molecular bridge that controls the synergistic action of dopamine and glutamate on striatal plasticity and behavioural responses to drugs of abuse. We found that concomitant stimulation of D1R and NMDAR drove complex formation between endogenous D1R and the GluN1 subunit of NMDAR. Conversely, preventing D1R/GluN1 association with a cell-permeable peptide (TAT-GluN1C1) left individual D1R and NMDAR-dependent signalling intact, but prevented D1R-mediated facilitation of NMDAR-calcium influx and subsequent ERK activation. Electrophysiological recordings in striatal slices from mice revealed that D1R/GluN1 complexes control the D1R-dependent enhancement of NMDAR currents and long-term potentiation in D1R-MSN. Finally, intra-striatal delivery of TAT-GluN1C1 did not affect acute responses to cocaine but reduced behavioural sensitization. Our findings uncover D1R/GluN1 complexes as a major substrate for the dopamine-glutamate interaction in MSN that is usurped by addictive drugs to elicit persistent behavioural alterations. They also identify D1R/GluN1 complexes as molecular targets with a therapeutic potential for the vast spectrum of psychiatric diseases associated with an imbalance between dopamine and glutamate transmission. PMID:25070539

  18. Associative, Bidirectional Changes in Neural Signaling Utilizing NMDA Receptor- and Endocannabinoid-Dependent Mechanisms

    Science.gov (United States)

    Li, Qin; Burrell, Brian D.

    2011-01-01

    Persistent, bidirectional changes in synaptic signaling (that is, potentiation and depression of the synapse) can be induced by the precise timing of individual pre- and postsynaptic action potentials. However, far less attention has been paid to the ability of paired trains of action potentials to elicit persistent potentiation or depression. We…

  19. Structural plasticity mechanisms and developmental psychiatric disorders

    OpenAIRE

    Dominique eMuller; Yann eBernardinelli; Irina eNikonenko

    2014-01-01

    Synaptic plasticity mechanisms are usually discussed in terms of changes in synaptic strength. The capacity of excitatory synapses to rapidly modify the membrane expression of glutamate receptors in an activity-dependent manner plays a critical role in learning and memory processes by re-distributing activity within neuronal networks. Recent work has however also shown that functional plasticity properties are associated with a rewiring of synaptic connections and a selective stabilization of...

  20. 淀粉样β-蛋白在阿尔茨海默病突触可塑性中的作用%Role of β-amyloid Protein in Synaptic Plasticity of Alzheimer’ s Disease

    Institute of Scientific and Technical Information of China (English)

    张锦辉; 郑琳琳

    2014-01-01

    Alzheimer ’ s disease ( AD) is a common type of dementia .Though it is closely related to age , its exact pathogenesis has still been unclear .Senile plaques will appear in the brain of the patient attacked by AD and the core component of the plaques is amyloid β-protein ( Aβ) .Aβdepositions abnormally in the brain may de-crease the synaptic plasticity and affect the hippocampal long -term potentiation .Studies have shown that the main component of Aβthat has neurotoxic effects is oligomers such as Aβ1-40 and Aβ1-42 etc.they can inactivate N-methyl-D-aspartate ( NMDA) receptor and abnormally increase the glutamate in brain mediated by NMDA re-ceptor , and finally reduce the learning and memory ability of the patient .%阿尔茨海默病是老年痴呆的常见类型,与年龄密切相关,目前AD的确切发病机制仍不十分清楚。 AD发生后脑内出现老年斑,其核心成分为淀粉样β-蛋白( amyloid β-peptide , Aβ)。 Aβ在脑内的异常沉积导致突触可塑性降低,影响海马长时程增强过程。研究表明Aβ发挥神经毒性作用主要是其寡聚体,如Aβ1-40和Aβ1-42等,使N-甲基-D-天冬氨酸( NMDA)的受体失活,导致NMDA受体介导的谷氨酸异常增高,最终体现为学习记忆能力下降。

  1. Terminal axonal arborization and synaptic bouton formation critically rely on abp1 and the arp2/3 complex.

    Directory of Open Access Journals (Sweden)

    Nicole Koch

    Full Text Available Neuronal network formation depends on properly timed and localized generation of presynaptic as well as postsynaptic structures. Although of utmost importance for understanding development and plasticity of the nervous system and neurodegenerative diseases, the molecular mechanisms that ensure the fine-control needed for coordinated establishment of pre- and postsynapses are still largely unknown. We show that the F-actin-binding protein Abp1 is prominently expressed in the Drosophila nervous system and reveal that Abp1 is an important regulator in shaping glutamatergic neuromuscular junctions (NMJs of flies. STED microscopy shows that Abp1 accumulations can be found in close proximity of synaptic vesicles and at the cell cortex in nerve terminals. Abp1 knock-out larvae have locomotion defects and underdeveloped NMJs that are characterized by a reduced number of both type Ib synaptic boutons and branches of motornerve terminals. Abp1 is able to indirectly trigger Arp2/3 complex-mediated actin nucleation and interacts with both WASP and Scar. Consistently, Arp2 and Arp3 loss-of-function also resulted in impairments of bouton formation and arborization at NMJs, i.e. fully phenocopied abp1 knock-out. Interestingly, neuron- and muscle-specific rescue experiments revealed that synaptic bouton formation critically depends on presynaptic Abp1, whereas the NMJ branching defects can be compensated for by restoring Abp1 functions at either side. In line with this presynaptic importance of Abp1, also presynaptic Arp2 and Arp3 are crucial for the formation of type Ib synaptic boutons. Interestingly, presynaptic Abp1 functions in NMJ formation were fully dependent on the Arp2/3 complex, as revealed by suppression of Abp1-induced synaptic bouton formation and branching of axon terminals upon presynaptic Arp2 RNAi. These data reveal that Abp1 and Arp2/3 complex-mediated actin cytoskeletal dynamics drive both synaptic bouton formation and NMJ branching. Our

  2. The 5-HT7 receptor triggers cerebellar long-term synaptic depression via PKC-MAPK.

    Science.gov (United States)

    Lippiello, Pellegrino; Hoxha, Eriola; Speranza, Luisa; Volpicelli, Floriana; Ferraro, Angela; Leopoldo, Marcello; Lacivita, Enza; Perrone-Capano, Carla; Tempia, Filippo; Miniaci, Maria Concetta

    2016-02-01

    The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum. PMID:26482421

  3. A Statistical Theory of Bidirectionality

    Science.gov (United States)

    DeLoach, Richard; Ulbrich, Norbert

    2013-01-01

    Original concepts related to the quantification and assessment of bidirectionality in strain-gage balances were introduced by Ulbrich in 2012. These concepts are extended here in three ways: 1) the metric originally proposed by Ulbrich is normalized, 2) a categorical variable is introduced in the regression analysis to account for load polarity, and 3) the uncertainty in both normalized and non-normalized bidirectionality metrics is quantified. These extensions are applied to four representative balances to assess the bidirectionality characteristics of each. The paper is tutorial in nature, featuring reviews of certain elements of regression and formal inference. Principal findings are that bidirectionality appears to be a common characteristic of most balance outputs and that unless it is taken into account, it is likely to consume the entire error budget of a typical balance calibration experiment. Data volume and correlation among calibration loads are shown to have a significant impact on the precision with which bidirectionality metrics can be assessed.

  4. Synaptic vesicle endocytosis.

    Science.gov (United States)

    Saheki, Yasunori; De Camilli, Pietro

    2012-09-01

    Neurons can sustain high rates of synaptic transmission without exhausting their supply of synaptic vesicles. This property relies on a highly efficient local endocytic recycling of synaptic vesicle membranes, which can be reused for hundreds, possibly thousands, of exo-endocytic cycles. Morphological, physiological, molecular, and genetic studies over the last four decades have provided insight into the membrane traffic reactions that govern this recycling and its regulation. These studies have shown that synaptic vesicle endocytosis capitalizes on fundamental and general endocytic mechanisms but also involves neuron-specific adaptations of such mechanisms. Thus, investigations of these processes have advanced not only the field of synaptic transmission but also, more generally, the field of endocytosis. This article summarizes current information on synaptic vesicle endocytosis with an emphasis on the underlying molecular mechanisms and with a special focus on clathrin-mediated endocytosis, the predominant pathway of synaptic vesicle protein internalization.

  5. Cognition and synaptic plasticity in diabetes mellitus

    NARCIS (Netherlands)

    Gispen, W.H.; Biessels, G.J.

    2000-01-01

    Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits are paralleled by neurophysiological and structural changes in the brain. In animal models of diabetes, impairments of spatial learning occur in association with dis

  6. 侧脑室注射氯胺酮降低成年SD大鼠海马区突触可塑性%Effect of ketamine injected into cerebro ventriles on synaptic plasticity of hippocampus in adult SD rats

    Institute of Scientific and Technical Information of China (English)

    郭东勇; 谭涛; 田心; 王国林

    2012-01-01

    Objective: To observe the effect of ketamine of intracerebroventricular injection to adult SD rats on LTP of hippocampus. Methods: 12 adult SD rats were randomly divided into group C and C-I. LTP was recorded after NS or ketamine(50μg) 5μL were injected into cerebro ventriles respectively. Results: 30 min after stimulation, PS amplitude in group C and C—I were (216.29±12.11)% and (138.04±6.50)% (P<0.05). 60 min after stimulation, PS amplitude were (202.33±11.53)% and (149.60±10.86)%(P<0.05). LTP in group C-I reduced obviously. Conclusion: Ketamine of intracerebroventricular injection reduces synaptic plasticity of hippocampus in adult SD rats.%目的:研究侧脑室注射氯胺酮对成年SD大鼠在体海马区长时程增强(LTP)的影响.方法:成年SD大鼠12只,随机分为实验组(C-1组)和对照组(C组),前者经右侧脑室注射50μg氯胺酮(生理盐水稀释至5μL),后者注射等量生理盐水后,记录在体海马区LTP.结果:高频刺激后30min时,C组和C-1组分别为条件刺激PS幅值的(216.29±12.11)%和(138.04±6.50)%(P<0.05);刺激后60min时,分别为(202.33±11.53)%和(149.60±10.86)%(P<0.05),C-1组LTP突触可塑性改变程度较对照组显著降低.结论:侧脑室注射氯胺酮可显著降低成年大鼠海马区突触可塑性.

  7. 术中机械通气对小鼠海马CA1区突触可塑性的影响%Effect of mechanical ventilation on synaptic plasticity in hippocampal CA1 region of mice

    Institute of Scientific and Technical Information of China (English)

    陈婷; 张宗泽; 陈畅; 彭勉; 许鑫; 陈凯; 王焱林

    2015-01-01

    目的 评价术中机械通气对小鼠海马CA1区突触可塑性的影响.方法 健康雄性C57BL/6小鼠36只,8~10周龄,体重20~25 g,采用随机数字表法,将其分成2组(n=18):对照组(C组)和机械通气组(M组).小鼠在麻醉后气管插管并行胫骨骨折切开复位内固定术.C组术后拔除气管导管,放入麻醉箱6h,通入1.5%异氟醚维持麻醉;M组术后继续机械通气6h,吸入1.5%异氟醚维持麻醉.于机械通气结束后2h、1和3d时,取6只小鼠进行恐惧条件化实验,记录僵直时间百分比.于机械通气结束后1d时取6只小鼠开始进行新物体识别实验,第4天时间隔5 min、2h和1d时,计算优先指数.于机械通气结束后1d时处死3只小鼠,取海马组织,电镜下观察海马超微结构,并记录突触数量.于机械通气结束后1d时处死3只小鼠,取全脑组织,进行高尔基染色,测定树突棘密度.结果 与C组比较,M组术后2h和1d时僵直时间百分比降低,不同时间间隔优先指数降低,海马CA1区突触数量减少,顶树突棘密度和基树突棘密度降低(P<0.01).结论 术中机械通气可改变小鼠海马CA1区突触可塑性.%Objective To evaluate the effect of mechanical ventilation on synaptic plasticity in hippocampal CA1 region of mice.Methods Thirty-six male C57BL/6 mice,aged 8-10 weeks,weighing 20-25 g,were randomly divided into 2 groups (n =18 each) using a random number table:control group (group C) and mechanical ventilation group (group M).After anesthesia,endotracheal intubation was carried out,and open reduction and internal fixation was performed after tibial fracture was induced in mice.In C group,the endotracheal tube was removed after operation,and then the mice were exposed to 1.5% isoflurane for 6 h in a chamber.In M group,the mice were mechanically ventilated continuously for 6 h,and 1.5% isoflurane was inhaled to maintain the level of anesthesia.At 2 h and 1 and 3 days after the end of ventilation,6 mice were

  8. Improved Bidirectional Exact Pattern Matching

    OpenAIRE

    Hussain, Iftikhar; Hassan Kazmi, Syed Zaki; Ali Khan, Israr; Mehmood, Rashid

    2013-01-01

    In this research, we present an improved version of Bidirectional (BD) exact pattern matching (EPM) algorithm to solve the problem of exact pattern matching. Improved-Bidirectional (IBD) exact pattern matching algorithm introduced a new idea of scanning partial text window (PTW) as well with the pattern to take decision of moving pattern to the right of partial text window. IBD algorithm compares the characters of pattern to selected text window (STW) from both sides simultaneously as BD....

  9. Extracellular ATP hydrolysis inhibits synaptic transmission by increasing ph buffering in the synaptic cleft.

    Directory of Open Access Journals (Sweden)

    Rozan Vroman

    2014-05-01

    Full Text Available Neuronal computations strongly depend on inhibitory interactions. One such example occurs at the first retinal synapse, where horizontal cells inhibit photoreceptors. This interaction generates the center/surround organization of bipolar cell receptive fields and is crucial for contrast enhancement. Despite its essential role in vision, the underlying synaptic mechanism has puzzled the neuroscience community for decades. Two competing hypotheses are currently considered: an ephaptic and a proton-mediated mechanism. Here we show that horizontal cells feed back to photoreceptors via an unexpected synthesis of the two. The first one is a very fast ephaptic mechanism that has no synaptic delay, making it one of the fastest inhibitory synapses known. The second one is a relatively slow (τ≈200 ms, highly intriguing mechanism. It depends on ATP release via Pannexin 1 channels located on horizontal cell dendrites invaginating the cone synaptic terminal. The ecto-ATPase NTPDase1 hydrolyses extracellular ATP to AMP, phosphate groups, and protons. The phosphate groups and protons form a pH buffer with a pKa of 7.2, which keeps the pH in the synaptic cleft relatively acidic. This inhibits the cone Ca²⁺ channels and consequently reduces the glutamate release by the cones. When horizontal cells hyperpolarize, the pannexin 1 channels decrease their conductance, the ATP release decreases, and the formation of the pH buffer reduces. The resulting alkalization in the synaptic cleft consequently increases cone glutamate release. Surprisingly, the hydrolysis of ATP instead of ATP itself mediates the synaptic modulation. Our results not only solve longstanding issues regarding horizontal cell to photoreceptor feedback, they also demonstrate a new form of synaptic modulation. Because pannexin 1 channels and ecto-ATPases are strongly expressed in the nervous system and pannexin 1 function is implicated in synaptic plasticity, we anticipate that this novel form

  10. Adult myelination:wrapping up neuronal plasticity

    Institute of Scientific and Technical Information of China (English)

    Megan ORourke; Robert Gasperini; Kaylene M.Young

    2014-01-01

    In this review, we outline the major neural plasticity mechanisms that have been identiifed in the adult central nervous system (CNS), and offer a perspective on how they regulate CNS function. In particular we examine how myelin plasticity can operate alongside neurogenesis and synaptic plasticity to inlfuence information processing and transfer in the mature CNS.

  11. Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission

    NARCIS (Netherlands)

    S.A. Spangler (Samantha); S.K. Schmitz (Sabine); J.T. Kevenaar (Josta); E. de Graaff (Esther); M. De Wit (Meike); J.A.A. Demmers (Jeroen); P.W. Toonen (Pim ); C.C. Hoogenraad (Casper)

    2013-01-01

    textabstractThe presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-α2 as a key organizer in this process. We show that liprin-α2 levels were r

  12. Synaptic connectivity in engineered neuronal networks.

    Science.gov (United States)

    Molnar, Peter; Kang, Jung-Fong; Bhargava, Neelima; Das, Mainak; Hickman, James J

    2014-01-01

    We have developed a method to organize cells in dissociated cultures using engineered chemical clues on a culture surface and determined their connectivity patterns. Although almost all elements of the synaptic transmission machinery can be studied separately in single cell models in dissociated cultures, the complex physiological interactions between these elements are usually lost. Thus, factors affecting synaptic transmission are generally studied in organotypic cultures, brain slices, or in vivo where the cellular architecture generally remains intact. However, by utilizing engineered neuronal networks complex phenomenon such as synaptic transmission or synaptic plasticity can be studied in a simple, functional, cell culture-based system. We have utilized self-assembled monolayers and photolithography to create the surface templates. Embryonic hippocampal cells, plated on the resultant patterns in serum-free medium, followed the surface clues and formed the engineered neuronal networks. Basic whole-cell patch-clamp electrophysiology was applied to characterize the synaptic connectivity in these engineered two-cell networks. The same technology has been used to pattern other cell types such as cardiomyocytes or skeletal muscle fibers.

  13. Synaptic theory of Replicator-like melioration

    Directory of Open Access Journals (Sweden)

    Yonatan Loewenstein

    2010-06-01

    Full Text Available According to the theory of Melioration, organisms in repeated choice settings shift their choice preference in favor of the alternative that provides the highest return. The goal of this paper is to explain how this learning behavior can emerge from microscopic changes in the efficacies of synapses, in the context of two-alternative repeated-choice experiment. I consider a large family of synaptic plasticity rules in which changes in synaptic efficacies are driven by the covariance between reward and neural activity. I construct a general framework that predicts the learning dynamics of any decision-making neural network that implements this synaptic plasticity rule and show that melioration naturally emerges in such networks. Moreover, the resultant learning dynamics follows the Replicator equation which is commonly used to phenomenologically describe changes in behavior in operant conditioning experiments. Several examples demonstrate how the learning rate of the network is affected by its properties and by the specifics of the plasticity rule. These results help bridge the gap between cellular physiology and learning behavior.

  14. Progress in neural plasticity

    Institute of Scientific and Technical Information of China (English)

    POO; Mu-Ming

    2010-01-01

    One of the properties of the nervous system is the use-dependent plasticity of neural circuits.The structure and function of neural circuits are susceptible to changes induced by prior neuronal activity,as reflected by short-and long-term modifications of synaptic efficacy and neuronal excitability.Regarded as the most attractive cellular mechanism underlying higher cognitive functions such as learning and memory,activity-dependent synaptic plasticity has been in the spotlight of modern neuroscience since 1973 when activity-induced long-term potentiation(LTP) of hippocampal synapses was first discovered.Over the last 10 years,Chinese neuroscientists have made notable contributions to the study of the cellular and molecular mechanisms of synaptic plasticity,as well as of the plasticity beyond synapses,including activity-dependent changes in intrinsic neuronal excitability,dendritic integration functions,neuron-glia signaling,and neural network activity.This work highlight some of these significant findings.

  15. Behavior of composite rigid frame bridge under bi-directional seismic excitations

    Directory of Open Access Journals (Sweden)

    Xiaogang Liu

    2014-02-01

    Full Text Available Pushover analysis and time history analysis are conducted to explore the bi-directional seismic behavior of composite steel-concrete rigid frame bridge, which is composed of RC piers and steel-concrete composite girders. Both longitudinal and transverse directions excitations are investigated using OpenSees. Firstly, the applicability of pushover analysis based on the fundamental mode is discussed. Secondly, an improved pushover analysis method considering the contribution of higher modes is proposed, and the applicability on composite rigid frame bridges under bi-directional earthquake is verified. Based on this method, an approach to predict the displacement responses of composite rigid frame bridge under random bi-directional seismic excitations by revising the elasto-plastic demand curve is also proposed. It is observed that the developed method yield a good estimate on the responses of composite rigid frame bridges under bi-directional seismic excitations.

  16. Regularly Controlled Bidirectional Linear Basic Grammars

    OpenAIRE

    Hogendorp, Jan Anne

    1990-01-01

    We investigate the bidirectional application of grammar productions -- i.e., using the productions in the reversed direction too -- to linear basic grammars. As in the case of regularly controlled bidirectional context-free grammars (or RCB grammars), we provide bidirectional linear basic grammars with a regular control language over the rules (i.e., productions and their corresponding reductions). Our main result shows that under the so-called RS/B/f-mode of derivation, bidirectionality give...

  17. Regularly Controlled Bidirectional Linear Basic Grammars

    NARCIS (Netherlands)

    Hogendorp, Jan Anne

    1990-01-01

    We investigate the bidirectional application of grammar productions -- i.e., using the productions in the reversed direction too -- to linear basic grammars. As in the case of regularly controlled bidirectional context-free grammars (or RCB grammars), we provide bidirectional linear basic grammars w

  18. Synaptic Vesicle Exocytosis

    OpenAIRE

    Südhof, Thomas C; Rizo, Josep

    2011-01-01

    Presynaptic nerve terminals release neurotransmitters by synaptic vesicle exocytosis. Membrane fusion mediating synaptic exocytosis and other intracellular membrane traffic is affected by a universal machinery that includes SNARE (for “soluble NSF-attachment protein receptor”) and SM (for “Sec1/Munc18-like”) proteins. During fusion, vesicular and target SNARE proteins assemble into an α-helical trans-SNARE complex that forces the two membranes tightly together, and SM proteins likely wrap aro...

  19. Synaptic depression creates a switch that controls the frequency of an oscillatory circuit

    OpenAIRE

    Nadim, Farzan; Manor, Yair; Kopell, Nancy; Marder, Eve

    1999-01-01

    Synaptic depression is a form of short-term plasticity exhibited by many synapses. Nonetheless, the functional significance of synaptic depression in oscillatory networks is not well understood. We show that, in a recurrent inhibitory network that includes an intrinsic oscillator, synaptic depression can give rise to two distinct modes of network operation. When the maximal conductance of the depressing synapse is small, the oscillation period is determined by the oscillator component. Increa...

  20. SNAP-29-mediated Modulation of Synaptic Transmission in Cultured Hippocampal Neurons*

    OpenAIRE

    Pan, Ping-Yue; Cai, Qian; Lin, Lin; Lu, Pei-Hua; Duan, Shumin; Sheng, Zu-Hang

    2005-01-01

    Identifying the molecules that regulate both the recycling of synaptic vesicles and the SNARE components required for fusion is critical for elucidating the molecular mechanisms underlying synaptic plasticity. SNAP-29 was initially isolated as a syntaxin-binding and ubiquitously expressed protein. Previous studies have suggested that SNAP-29 inhibits SNARE complex disassembly, thereby reducing synaptic transmission in cultured superior cervical ganglion neurons in an activity-dependent manner...

  1. Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

    Directory of Open Access Journals (Sweden)

    Joshua G.A Pinto

    2015-02-01

    Full Text Available Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin and found that synaptic development in human primary visual cortex continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the 4 proteins and include a stage during early development (<1 year when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the first year or two of life. A multidimensional analysis (principle component analysis showed that most of the variance was captured by the sum of the 4 synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic.

  2. Regulation of spike timing-dependent plasticity of olfactory inputs in mitral cells in the rat olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Teng-Fei Ma

    Full Text Available The recent history of activity input onto granule cells (GCs in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON inputs to mitral cells (MCs. Here we found that the repetitive stimulation of two distinct excitatory inputs to the GCs induced a persistent modification of lateral inhibition in MCs in opposing directions. This bidirectional modification of inhibitory inputs differentially regulated the subsequent synaptic plasticity of the excitatory ON inputs to the MCs, which was induced by the repetitive pairing of excitatory postsynaptic potentials (EPSPs with postsynaptic bursts. The regulation of spike timing-dependent plasticity (STDP was achieved by the regulation of the inter-spike-interval (ISI of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb.

  3. The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag

    OpenAIRE

    Szabó, Eszter C.; Manguinhas, Rita; Fonseca, Rosalina

    2016-01-01

    Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only...

  4. Synaptic Democracy and Vesicular Transport in Axons

    Science.gov (United States)

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  5. Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

    Science.gov (United States)

    Blanco, Wilfredo; Pereira, Catia M; Cota, Vinicius R; Souza, Annie C; Rennó-Costa, César; Santos, Sharlene; Dias, Gabriella; Guerreiro, Ana M G; Tort, Adriano B L; Neto, Adrião D; Ribeiro, Sidarta

    2015-05-01

    Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic

  6. Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

    Directory of Open Access Journals (Sweden)

    Wilfredo Blanco

    2015-05-01

    Full Text Available Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS followed by a rebound during rapid-eye-movement sleep (REM. The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes

  7. Synaptic devices based on purely electronic memristors

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Ruobing [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); Institute of Materials Science, School of Materials Science and Engineering, Shanghai University, Shanghai 200072 (China); Li, Jun; Zhuge, Fei, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Zhu, Liqiang; Liang, Lingyan; Zhang, Hongliang; Gao, Junhua; Cao, Hongtao, E-mail: zhugefei@nimte.ac.cn, E-mail: h-cao@nimte.ac.cn; Fu, Bing; Li, Kang [Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China)

    2016-01-04

    Memristive devices have been widely employed to emulate biological synaptic behavior. In these cases, the memristive switching generally originates from electrical field induced ion migration or Joule heating induced phase change. In this letter, the Ti/ZnO/Pt structure was found to show memristive switching ascribed to a carrier trapping/detrapping of the trap sites (e.g., oxygen vacancies or zinc interstitials) in ZnO. The carrier trapping/detrapping level can be controllably adjusted by regulating the current compliance level or voltage amplitude. Multi-level conductance states can, therefore, be realized in such memristive device. The spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in this type of synaptic device. Compared with filamentary-type memristive devices, purely electronic memristors have potential to reduce their energy consumption and work more stably and reliably, since no structural distortion occurs.

  8. Synaptic devices based on purely electronic memristors

    Science.gov (United States)

    Pan, Ruobing; Li, Jun; Zhuge, Fei; Zhu, Liqiang; Liang, Lingyan; Zhang, Hongliang; Gao, Junhua; Cao, Hongtao; Fu, Bing; Li, Kang

    2016-01-01

    Memristive devices have been widely employed to emulate biological synaptic behavior. In these cases, the memristive switching generally originates from electrical field induced ion migration or Joule heating induced phase change. In this letter, the Ti/ZnO/Pt structure was found to show memristive switching ascribed to a carrier trapping/detrapping of the trap sites (e.g., oxygen vacancies or zinc interstitials) in ZnO. The carrier trapping/detrapping level can be controllably adjusted by regulating the current compliance level or voltage amplitude. Multi-level conductance states can, therefore, be realized in such memristive device. The spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in this type of synaptic device. Compared with filamentary-type memristive devices, purely electronic memristors have potential to reduce their energy consumption and work more stably and reliably, since no structural distortion occurs.

  9. Synaptic remodeling of neuronal circuits in early retinal degeneration

    Science.gov (United States)

    Soto, Florentina; Kerschensteiner, Daniel

    2015-01-01

    Photoreceptor degenerations are a major cause of blindness and among the most common forms of neurodegeneration in humans. Studies of mouse models revealed that synaptic dysfunction often precedes photoreceptor degeneration, and that abnormal synaptic input from photoreceptors to bipolar cells causes circuits in the inner retina to become hyperactive. Here, we provide a brief overview of frequently used mouse models of photoreceptor degenerations. We then discuss insights into circuit remodeling triggered by early synaptic dysfunction in the outer and hyperactivity in the inner retina. We discuss these insights in the context of other experimental manipulations of synaptic function and activity. Knowledge of the plasticity and early remodeling of retinal circuits will be critical for the design of successful vision rescue strategies. PMID:26500497

  10. Synaptic remodeling of neuronal circuits in early retinal degeneration

    Directory of Open Access Journals (Sweden)

    Florentina eSoto

    2015-10-01

    Full Text Available Photoreceptor degenerations are a major cause of blindness and among the most common forms of neurodegeneration in humans. Studies of mouse models revealed that synaptic dysfunction often precedes photoreceptor degeneration, and that abnormal synaptic input from photoreceptors to bipolar cells causes circuits in the inner retina to become hyperactive. Here, we provide a brief overview of frequently used mouse models of photoreceptor degenerations. We then discuss insights into circuit remodeling triggered by early synaptic dysfunction in the outer and hyperactivity in the inner retina. We discuss these insights in the context of other experimental manipulations of synaptic function and activity. Knowledge of the plasticity and early remodeling of retinal circuits will be critical for the design of successful vision rescue strategies.

  11. Synapse geometry and receptor dynamics modulate synaptic strength.

    Directory of Open Access Journals (Sweden)

    Dominik Freche

    Full Text Available Synaptic transmission relies on several processes, such as the location of a released vesicle, the number and type of receptors, trafficking between the postsynaptic density (PSD and extrasynaptic compartment, as well as the synapse organization. To study the impact of these parameters on excitatory synaptic transmission, we present a computational model for the fast AMPA-receptor mediated synaptic current. We show that in addition to the vesicular release probability, due to variations in their release locations and the AMPAR distribution, the postsynaptic current amplitude has a large variance, making a synapse an intrinsic unreliable device. We use our model to examine our experimental data recorded from CA1 mice hippocampal slices to study the differences between mEPSC and evoked EPSC variance. The synaptic current but not the coefficient of variation is maximal when the active zone where vesicles are released is apposed to the PSD. Moreover, we find that for certain type of synapses, receptor trafficking can affect the magnitude of synaptic depression. Finally, we demonstrate that perisynaptic microdomains located outside the PSD impacts synaptic transmission by regulating the number of desensitized receptors and their trafficking to the PSD. We conclude that geometrical modifications, reorganization of the PSD or perisynaptic microdomains modulate synaptic strength, as the mechanisms underlying long-term plasticity.

  12. Striatal plasticity and basal ganglia circuit function.

    Science.gov (United States)

    Kreitzer, Anatol C; Malenka, Robert C

    2008-11-26

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways, which are distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive motor control and procedural memory. Here, we review current understanding of synaptic plasticity in the striatum and its role in the physiology and pathophysiology of basal ganglia function. PMID:19038213

  13. Bidirectional Microglia-Neuron Communication in the Healthy Brain

    Directory of Open Access Journals (Sweden)

    Ukpong B. Eyo

    2013-01-01

    Full Text Available Unlike other resident neural cells that are of neuroectodermal origin, microglia are resident neural cells of mesodermal origin. Traditionally recognized for their immune functions during disease, new roles are being attributed to these cells in the development and maintenance of the central nervous system (CNS including specific communication with neurons. In this review, we highlight some of the recent findings on the bidirectional interaction between neurons and microglia. We discuss these interactions along two lines. First, we review data that suggest that microglial activity is modulated by neuronal signals, focusing on evidence that (i neurons are capable of regulating microglial activation state and influence basal microglial activities; (ii classic neurotransmitters affect microglial behavior; (iii chemotactic signals attract microglia during acute neuronal injury. Next, we discuss some of the recent data on how microglia signal to neurons. Signaling mechanisms include (i direct physical contact of microglial processes with neuronal elements; (ii microglial regulation of neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In addition, we discuss the use of microglial depletion strategies in studying the role of microglia in neuronal development and synaptic physiology. Deciphering the mechanisms of bidirectional microglial-neuronal communication provides novel insights in understanding microglial function in both the healthy and diseased brain.

  14. Synapse number and synaptic efficacy are regulated by presynaptic cAMP and protein kinase A.

    Science.gov (United States)

    Munno, David W; Prince, David J; Syed, Naweed I

    2003-05-15

    The mechanisms by which neurons regulate the number and strength of synapses during development and synaptic plasticity have not yet been defined fully. This lack of fundamental knowledge in the fields of neurodevelopment and synaptic plasticity can be attributed, in part, to compensatory mechanisms by which neurons accommodate for the loss of function in their synaptic partners. This is generally achieved either by scaling up neuronal transmitter release capabilities or by enhancing the postsynaptic responsiveness. Here, we demonstrate that regulation of synaptic strength and number between identified Lymnaea neurons visceral dorsal 4 (VD4, the presynaptic cell) and left pedal dorsal 1 (LPeD1, the postsynaptic cell) requires presynaptic activation of a cAMP-PKA-dependent signal. Experimental activation of the cAMP-PKA pathway resulted in reduced synaptic efficacy, whereas inhibition of the cAMP-PKA cascade permitted hyperinnervation and an overall enhancement of synaptic strength. Because synaptic transmission between VD4 and LPeD1 does not require a cAMP-PKA pathway, our data show that these messengers may play a novel role in regulating the synaptic efficacy during early synaptogenesis and plasticity.

  15. Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Fuenzalida, Marco; Espinoza, Claudia; Pérez, Miguel Ángel; Tapia-Rojas, Cheril; Cuitino, Loreto; Brandan, Enrique; Inestrosa, Nibaldo C

    2016-02-01

    The dystrophin-associated glycoprotein complex (DGC) that connects the cytoskeleton, plasma membrane and the extracellular matrix has been related to the maintenance and stabilization of channels and synaptic receptors, which are both essential for synaptogenesis and synaptic transmission. The dystrophin-deficient (mdx) mouse model of Duchenne muscular dystrophy (DMD) exhibits a significant reduction in hippocampal GABA efficacy, which may underlie the altered synaptic function and abnormal hippocampal long-term plasticity exhibited by mdx mice. Emerging studies have implicated Wnt signaling in the modulation of synaptic efficacy, neuronal plasticity and cognitive function. We report here that the activation of the non-canonical Wnt-5a pathway and Andrographolide, improves hippocampal mdx GABAergic efficacy by increasing the number of inhibitory synapses and GABA(A) receptors or GABA release. These results indicate that Wnt signaling modulates GABA synaptic efficacy and could be a promising novel target for DMD cognitive therapy. PMID:26626079

  16. Neural Plasticity in the Gustatory System

    OpenAIRE

    Hill, David L.

    2004-01-01

    Sensory systems adapt to changing environmental influences by coordinated alterations in structure and function. These alterations are referred to as plastic changes. The gustatory system displays numerous plastic changes even in receptor cells. This review focuses on the plasticity of gustatory structures through the first synaptic relay in the brain. Unlike other sensory systems, there is a remarkable amount of environmentally induced changes in these peripheral-most neural structures. The ...

  17. Differential Dendritic Integration of Synaptic Potentials and Calcium in Cerebellar Interneurons.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Abrahamsson, Therése; Cathala, Laurence; DiGregorio, David A

    2016-08-17

    Dendritic voltage integration determines the transformation of synaptic inputs into output firing, while synaptic calcium integration drives plasticity mechanisms thought to underlie memory storage. Dendritic calcium integration has been shown to follow the same synaptic input-output relationship as dendritic voltage, but whether similar operations apply to neurons exhibiting sublinear voltage integration is unknown. We examined the properties and cellular mechanisms of these dendritic operations in cerebellar molecular layer interneurons using dendritic voltage and calcium imaging, in combination with synaptic stimulation or glutamate uncaging. We show that, while synaptic potentials summate sublinearly, concomitant dendritic calcium signals summate either linearly or supralinearly depending on the number of synapses activated. The supralinear dendritic calcium triggers a branch-specific, short-term suppression of neurotransmitter release that alters the pattern of synaptic activation. Thus, differential voltage and calcium integration permits dynamic regulation of neuronal input-output transformations without altering intrinsic nonlinear integration mechanisms.

  18. Differential Dendritic Integration of Synaptic Potentials and Calcium in Cerebellar Interneurons.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Abrahamsson, Therése; Cathala, Laurence; DiGregorio, David A

    2016-08-17

    Dendritic voltage integration determines the transformation of synaptic inputs into output firing, while synaptic calcium integration drives plasticity mechanisms thought to underlie memory storage. Dendritic calcium integration has been shown to follow the same synaptic input-output relationship as dendritic voltage, but whether similar operations apply to neurons exhibiting sublinear voltage integration is unknown. We examined the properties and cellular mechanisms of these dendritic operations in cerebellar molecular layer interneurons using dendritic voltage and calcium imaging, in combination with synaptic stimulation or glutamate uncaging. We show that, while synaptic potentials summate sublinearly, concomitant dendritic calcium signals summate either linearly or supralinearly depending on the number of synapses activated. The supralinear dendritic calcium triggers a branch-specific, short-term suppression of neurotransmitter release that alters the pattern of synaptic activation. Thus, differential voltage and calcium integration permits dynamic regulation of neuronal input-output transformations without altering intrinsic nonlinear integration mechanisms. PMID:27537486

  19. Alzheimer's disease: synaptic dysfunction and Abeta

    LENUS (Irish Health Repository)

    Shankar, Ganesh M

    2009-11-23

    Abstract Synapse loss is an early and invariant feature of Alzheimer\\'s disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid β-protein (Aβ) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Aβ are mediators of synaptic compromise. We also discuss the possible mechanisms of Aβ synaptotoxicity and potential targets for therapeutic intervention.

  20. Abnormal Bidirectional Plasticity-Like Effects in Parkinson's Disease

    Science.gov (United States)

    Huang, Ying-Zu; Rothwell, John C.; Lu, Chin-Song; Chuang, Wen-Li; Chen, Rou-Shayn

    2011-01-01

    Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that…

  1. Bidirectional power converter control electronics

    Science.gov (United States)

    Mildice, J. W.

    1987-01-01

    The object of this program was to design, build, test, and deliver a set of control electronics suitable for control of bidirectional resonant power processing equipment of the direct output type. The program is described, including the technical background, and results discussed. Even though the initial program tested only the logic outputs, the hardware was subsequently tested with high-power breadboard equipment, and in the testbed of NASA contract NAS3-24399. The completed equipment is now operating as part of the Space Station Power System Test Facility at NASA Lewis Research Center.

  2. Heterosynaptic Plasticity: Multiple Mechanisms and Multiple Roles

    Science.gov (United States)

    Chistiakova, Marina; Bannon, Nicholas M.; Bazhenov, Maxim; Volgushev, Maxim

    2016-01-01

    Plasticity is a universal property of synapses. It is expressed in a variety of forms mediated by a multitude of mechanisms. Here we consider two broad kinds of plasticity that differ in their requirement for presynaptic activity during the induction. Homosynaptic plasticity occurs at synapses that were active during the induction. It is also called input specific or associative, and it is governed by Hebbian-type learning rules. Heterosynaptic plasticity can be induced by episodes of strong postsynaptic activity also at synapses that were not active during the induction, thus making any synapse at a cell a target to heterosynaptic changes. Both forms can be induced by typical protocols used for plasticity induction and operate on the same time scales but have differential computational properties and play different roles in learning systems. Homosynaptic plasticity mediates associative modifications of synaptic weights. Heterosynaptic plasticity counteracts runaway dynamics introduced by Hebbian-type rules and balances synaptic changes. It provides learning systems with stability and enhances synaptic competition. We conclude that homosynaptic and heterosynaptic plasticity represent complementary properties of modifiable synapses, and both are necessary for normal operation of neural systems with plastic synapses. PMID:24727248

  3. Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures

    OpenAIRE

    Koizumi, Schuichi; Fujishita, Kayoko; Tsuda, Makoto; Shigemoto-Mogami, Yukari; Inoue, Kazuhide

    2003-01-01

    Originally ascribed passive roles in the CNS, astrocytes are now known to have an active role in the regulation of synaptic transmission. Neuronal activity can evoke Ca2+ transients in astrocytes, and Ca2+ transients in astrocytes can evoke changes in neuronal activity. The excitatory neurotransmitter glutamate has been shown to mediate such bidirectional communication between astrocytes and neurons. We demonstrate here that ATP, a primary mediator of intercellular Ca2+ signaling among astroc...

  4. Cholinergic-mediated IP3-receptor activation induces long-lasting synaptic enhancement in CA1 pyramidal neurons

    OpenAIRE

    Fernández de Sevilla, D.; Núñez Molina, Ángel; Borde, M.; Malinow, R.; Buño, Washinton

    2008-01-01

    Cholinergic-glutamatergic interactions influence forms of synaptic plasticity that are thought to mediate memory and learning. We tested in vitro the induction of long-lasting synaptic enhancement at Schaffer collaterals by acetylcholine (ACh) at the apical dendrite of CA1 pyramidal neurons and in vivo by stimulation of cholinergic afferents. In vitro ACh induced a Ca2+ wave and synaptic enhancement mediated by insertion of AMPA receptors in spines. Activation of muscarinic ACh receptors (mAC...

  5. Effects of ginsenoside on synaptic plasticity of freely moving rats and its mechanism of action%人参皂甙Rg1对自由活动大鼠突触可塑性的影响及其作用机制

    Institute of Scientific and Technical Information of China (English)

    王晓英; 张均田

    2001-01-01

    目的:研究人参皂甙Rg1对自由活动大鼠突触功能可塑性的影响及作用机制.方法:应用细胞外微电极记录技术,大鼠埋植电极后d 6予以Rg1(10,30 mg/kg,ip)12 d,记录(直至停药后d 3)其齿状回群体峰电位(PS).大鼠给予Rg1(10,30mg/kg,ip)12 d,据Timm染色法观察海马CA3区苔藓纤维出芽情况.以免疫组化技术检测齿状回颗粒细胞层GAP-43表达水平.结果:1)Rg1可显著降低诱发PS的阈值,提高清醒自由活动大鼠的突触传递效能,诱导LTP形成,停药3 d后,LTP仍可维持.2)Rg1组大鼠齿状回颗粒细胞层及齿状回门区GAP-43表达显著增加.3)Timm染色显示海马CA3区苔藓纤维出芽增加.结论:Rg1可使自由活动大鼠PP-DG突触传递效能发生以LTP为主的可塑性变化,其机制为齿状回颗粒细胞GAP-43表达增加,其投射靶区海马CA3苔藓纤维明显出芽增加,这呈正反馈性增强了突触传递效能.%AIM: To investigate the effect and mechanism of gin senoside Rg1 on synaptic plasticity of freely moving rats. METHODS: SD rats were chronically implanted with a stimulation electrode in the perforant path (PP) of hip pocampus and a recording electrode in the granule cell of dentate gyrus. After administration of ginsenoside Rg1 (10, 30 mg/kg, ip) for 12 d, extracellular recording technique was used to record the population spike (PS). Mossy fiber (MF) sprouting was measured using Timm's staining, and an immunohistochemical technique was used to detect the expression of presynaptic growth-associated protein 43 (GAP-43). RESULTS: Rg1 could signifi cantly increase the sensitivity of evoking PS, the ampli tude of PS and induce PP-DG long-term potentiation (LTP) in the dentate gyms (DG) of freely moving rats. In the meantime, Rg1 accelerated MF sprouting in CA3 cell field of hippocampus. The expression level of GAP-43 was elevated in granule cell layer and hilus of DG of Rgb-treated rats. CONCLUSION: The

  6. A targeted glycan-related gene screen reveals heparan sulfate proteoglycan sulfation regulates WNT and BMP trans-synaptic signaling.

    Directory of Open Access Journals (Sweden)

    Neil Dani

    Full Text Available A Drosophila transgenic RNAi screen targeting the glycan genome, including all N/O/GAG-glycan biosynthesis/modification enzymes and glycan-binding lectins, was conducted to discover novel glycan functions in synaptogenesis. As proof-of-product, we characterized functionally paired heparan sulfate (HS 6-O-sulfotransferase (hs6st and sulfatase (sulf1, which bidirectionally control HS proteoglycan (HSPG sulfation. RNAi knockdown of hs6st and sulf1 causes opposite effects on functional synapse development, with decreased (hs6st and increased (sulf1 neurotransmission strength confirmed in null mutants. HSPG co-receptors for WNT and BMP intercellular signaling, Dally-like Protein and Syndecan, are differentially misregulated in the synaptomatrix of these mutants. Consistently, hs6st and sulf1 nulls differentially elevate both WNT (Wingless; Wg and BMP (Glass Bottom Boat; Gbb ligand abundance in the synaptomatrix. Anterograde Wg signaling via Wg receptor dFrizzled2 C-terminus nuclear import and retrograde Gbb signaling via synaptic MAD phosphorylation and nuclear import are differentially activated in hs6st and sulf1 mutants. Consequently, transcriptional control of presynaptic glutamate release machinery and postsynaptic glutamate receptors is bidirectionally altered in hs6st and sulf1 mutants, explaining the bidirectional change in synaptic functional strength. Genetic correction of the altered WNT/BMP signaling restores normal synaptic development in both mutant conditions, proving that altered trans-synaptic signaling causes functional differentiation defects.

  7. A trans-synaptic nanocolumn aligns neurotransmitter release to receptors.

    Science.gov (United States)

    Tang, Ai-Hui; Chen, Haiwen; Li, Tuo P; Metzbower, Sarah R; MacGillavry, Harold D; Blanpied, Thomas A

    2016-08-11

    Synaptic transmission is maintained by a delicate, sub-synaptic molecular architecture, and even mild alterations in synapse structure drive functional changes during experience-dependent plasticity and pathological disorders. Key to this architecture is how the distribution of presynaptic vesicle fusion sites corresponds to the position of receptors in the postsynaptic density. However, while it has long been recognized that this spatial relationship modulates synaptic strength, it has not been precisely described, owing in part to the limited resolution of light microscopy. Using localization microscopy, here we show that key proteins mediating vesicle priming and fusion are mutually co-enriched within nanometre-scale subregions of the presynaptic active zone. Through development of a new method to map vesicle fusion positions within single synapses in cultured rat hippocampal neurons, we find that action-potential-evoked fusion is guided by this protein gradient and occurs preferentially in confined areas with higher local density of Rab3-interacting molecule (RIM) within the active zones. These presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins, suggesting the existence of a trans-synaptic molecular 'nanocolumn'. Thus, we propose that the nanoarchitecture of the active zone directs action-potential-evoked vesicle fusion to occur preferentially at sites directly opposing postsynaptic receptor-scaffold ensembles. Remarkably, NMDA receptor activation triggered distinct phases of plasticity in which postsynaptic reorganization was followed by trans-synaptic nanoscale realignment. This architecture suggests a simple organizational principle of central nervous system synapses to maintain and modulate synaptic efficiency. PMID:27462810

  8. Generalized plasticity

    CERN Document Server

    Yu, Mao-Hong

    2006-01-01

    Dealing with the plasticity of materials and structures, this book is an expansion of the "Unified Strength Theory to Plasticity Theory", leading to a unified treatment of metal plasticity and plasticity of geomaterials. It includes the metal plasticity for Tresca materials, Huber-von-Mises materials and twin-shear materials.

  9. Bidirectional waveguide coupling with plasmonic Fano nanoantennas

    International Nuclear Information System (INIS)

    We introduce the concept of a bidirectional, compact single-element Fano nanoantenna that allows for directional coupling of light in opposite directions of a high-index dielectric waveguide for two different operation wavelengths. We utilize a Fano resonance to tailor the radiation phases of a gold nanodisk and a nanoslit that is inscribed into the nanodisk to realize bidirectional scattering. We show that this Fano nanoantenna operates as a bidirectional waveguide coupler at telecommunication wavelengths and, thus, is ideally suitable for integrated wavelength-selective light demultiplexing

  10. Bidirectional waveguide coupling with plasmonic Fano nanoantennas

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Rui; Decker, Manuel, E-mail: manuel.decker@anu.edu.au; Staude, Isabelle; Neshev, Dragomir N.; Kivshar, Yuri S. [Nonlinear Physics Centre and Centre for Ultrahigh Bandwidth Devices for Optical Systems (CUDOS), Research School of Physics and Engineering, The Australian National University, Canberra ACT 0200 (Australia)

    2014-08-04

    We introduce the concept of a bidirectional, compact single-element Fano nanoantenna that allows for directional coupling of light in opposite directions of a high-index dielectric waveguide for two different operation wavelengths. We utilize a Fano resonance to tailor the radiation phases of a gold nanodisk and a nanoslit that is inscribed into the nanodisk to realize bidirectional scattering. We show that this Fano nanoantenna operates as a bidirectional waveguide coupler at telecommunication wavelengths and, thus, is ideally suitable for integrated wavelength-selective light demultiplexing.

  11. Homeostatic role of heterosynaptic plasticity: Models and experiments

    Directory of Open Access Journals (Sweden)

    Marina eChistiakova

    2015-07-01

    Full Text Available Homosynaptic Hebbian-type plasticity provides a cellular mechanism of learning and refinement of connectivity during development in a variety of biological systems. In this review we argue that a complimentary form of plasticity - heterosynaptic plasticity - represents a necessary cellular component for homeostatic regulation of synaptic weights and neuronal activity. The required properties of a homeostatic mechanism which acutely constrains the runaway dynamics imposed by Hebbian associative plasticity have been well-articulated by theoretical and modeling studies. Such mechanism(s should robustly support the stability of operation of neuronal networks and synaptic competition, include changes at non-active synapses, and operate on a similar time scale to Hebbian-type plasticity. The experimentally observed properties of heterosynaptic plasticity have introduced it as a strong candidate to fulfill this homeostatic role. Subsequent modeling studies which incorporate heterosynaptic plasticity into model neurons with Hebbian synapses (utilizing an STDP learning rule have confirmed its ability to robustly provide stability and competition. In contrast, properties of homeostatic synaptic scaling, which is triggered by extreme and long lasting (hours and days changes of neuronal activity, do not fit two crucial requirements for a hypothetical homeostatic mechanism needed to provide stability of operation in the face of on-going synaptic changes driven by Hebbian-type learning rules. Both the trigger and the time scale of homeostatic synaptic scaling are fundamentally different from those of the Hebbian-type plasticity. We conclude that heterosynaptic plasticity, which is triggered by the same episodes of strong postsynaptic activity and operates on the same time scale as Hebbian-type associative plasticity, is ideally suited to serve homeostatic role during on-going synaptic plasticity.

  12. Synaptic scaling enables dynamically distinct short- and long-term memory formation.

    Directory of Open Access Journals (Sweden)

    Christian Tetzlaff

    2013-10-01

    Full Text Available Memory storage in the brain relies on mechanisms acting on time scales from minutes, for long-term synaptic potentiation, to days, for memory consolidation. During such processes, neural circuits distinguish synapses relevant for forming a long-term storage, which are consolidated, from synapses of short-term storage, which fade. How time scale integration and synaptic differentiation is simultaneously achieved remains unclear. Here we show that synaptic scaling - a slow process usually associated with the maintenance of activity homeostasis - combined with synaptic plasticity may simultaneously achieve both, thereby providing a natural separation of short- from long-term storage. The interaction between plasticity and scaling provides also an explanation for an established paradox where memory consolidation critically depends on the exact order of learning and recall. These results indicate that scaling may be fundamental for stabilizing memories, providing a dynamic link between early and late memory formation processes.

  13. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Jarod Swant

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  14. Plastic Surgery

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Plastic Surgery KidsHealth > For Teens > Plastic Surgery Print A ... her forehead lightened with a laser? What Is Plastic Surgery? Just because the name includes the word " ...

  15. Precise Synaptic Efficacy Alignment Suggests Potentiation Dominated Learning

    OpenAIRE

    Hartmann, Christoph; Miner, Daniel C.; Triesch, Jochen

    2016-01-01

    Recent evidence suggests that parallel synapses from the same axonal branch onto the same dendritic branch have almost identical strength. It has been proposed that this alignment is only possible through learning rules that integrate activity over long time spans. However, learning mechanisms such as spike-timing-dependent plasticity (STDP) are commonly assumed to be temporally local. Here, we propose that the combination of temporally local STDP and a multiplicative synaptic normalization m...

  16. Recent advances in understanding synaptic abnormalities in Rett syndrome

    OpenAIRE

    Michael Johnston; Blue, Mary E.; Sakkubai Naidu

    2015-01-01

    Rett syndrome is an extremely disabling X-linked nervous system disorder that mainly affects girls in early childhood and causes autism-like behavior, severe intellectual disability, seizures, sleep disturbances, autonomic instability, and other disorders due to mutations in the MeCP2 (methyl CpG-binding protein 2) transcription factor. The disorder targets synapses and synaptic plasticity and has been shown to disrupt the balance between glutamate excitatory synapses and GABAergic inhibitory...

  17. Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle

    OpenAIRE

    Wilfredo Blanco; Catia M Pereira; Vinicius R Cota; Annie C Souza; César Rennó-Costa; Sharlene Santos; Gabriella Dias; Guerreiro, Ana M. G.; Tort, Adriano B. L.; Adrião D Neto; Sidarta Ribeiro

    2015-01-01

    Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states...

  18. Synaptic membrane rafts: traffic lights for local neurotrophin signalling?

    Directory of Open Access Journals (Sweden)

    Barbara eZonta

    2013-10-01

    Full Text Available Lipid rafts, cholesterol and lipid rich microdomains, are believed to play important roles as platforms for the partitioning of transmembrane and synaptic proteins involved in synaptic signalling, plasticity and maintenance. There is increasing evidence of a physical interaction between post-synaptic densities and post-synaptic lipid rafts. Localization of proteins within lipid rafts is highly regulated, and therefore lipid rafts may function as traffic lights modulating and fine-tuning neuronal signalling. The tyrosine kinase neurotrophin receptors (Trk and the low-affinity p75 neurotrophin receptor (p75NTR are enriched in neuronal lipid rafts together with the intermediates of downstream signalling pathways, suggesting a possible role of rafts in neurotrophin signalling. Moreover, neurotrophins and their receptors are involved in the regulation of cholesterol metabolism. Cholesterol is an important component of lipid rafts and its depletion leads to gradual loss of synapses, underscoring the importance of lipid rafts for proper neuronal function. Here, we review and discuss the idea that translocation of neurotrophin receptors in synaptic rafts may account for the selectivity of their transduced signals.

  19. Pedestrians rotation measurement in bidirectional streams

    CERN Document Server

    Feliciani, Claudio

    2016-01-01

    This study presents an experimental measurement of pedestrians' body rotation in bidirectional streams. A mock-up corridor monitored using a camera placed on azimuthal position is used to study pedestrians' behavior in unidirectional and bidirectional flows. Additionally, a commercial tablet is fixed on the chest of sample pedestrians to examine their body rotation (or yawing) which cannot be obtained using position tracking alone. Angular velocity is recorded and simultaneously stored in a central location using a wireless network, thus allowing the analysis of body movements with a high sampling rate and a limited delay. To investigate the influence of major/minor flow proportion (flow-ratio) on bidirectional streams two different situations were tested: the balanced configuration (with equal flows in both directions) and an unbalanced configuration (with different major and minor flow). Results clearly show that unidirectional flow is more stable compared to the bidirectional case, requiring less time to c...

  20. Bidirectional reflection effects in practical integrating spheres.

    Science.gov (United States)

    Mahan, J R; Walker, J A; Stancil, M M

    2015-10-20

    Integrating spheres play a central role in radiometric instrument calibration, surface optical property measurement, and radiant source characterization. Our work involves a simulation, based on the Monte Carlo ray-trace (MCRT) of bidirectional reflections within a practical integrating sphere pierced with two viewing ports. We used data from the literature to create an empirical model for the bidirectional reflection distribution function (BRF) of Spectralon suitable for use in the MCRT environment. The ratio of power escaping through the two openings is shown to vary linearly with wall absorptivity for both diffuse and bidirectional reflections. The sensitivity of this ratio to absorptivity is shown to be less when reflections are weakly bidirectional. PMID:26560384

  1. Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA

    OpenAIRE

    Liu, Shuai; Globa, Andrea K.; Mills, Fergil; Naef, Lindsay; Qiao, Min; Bamji, Shernaz X.; Borgland, Stephanie L.

    2016-01-01

    Consumption of palatable food or food-related advertising can prime increased food intake, potentially leading to overeating. We show that short-term exposure to palatable foods induces long-lasting synaptic plasticity in mesolimbic dopamine neurons. Furthermore, short-term exposure to sweetened high-fat food can drive food approach behaviors and consumption days after the initial exposure. Suppressing excitatory synaptic transmission in the ventral tegmental area can reverse increased food a...

  2. Structural plasticity mechanisms and developmental psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Dominique eMuller

    2014-11-01

    Full Text Available Synaptic plasticity mechanisms are usually discussed in terms of changes in synaptic strength. The capacity of excitatory synapses to rapidly modify the membrane expression of glutamate receptors in an activity-dependent manner plays a critical role in learning and memory processes by re-distributing activity within neuronal networks. Recent work has however also shown that functional plasticity properties are associated with a rewiring of synaptic connections and a selective stabilization of activated synapses. These structural aspects of plasticity have the potential to continuously modify the organization of synaptic networks and thereby introduce specificity in the wiring diagram of cortical circuits. Recent work has started to unravel some of the molecular mechanisms that underlie these properties of structural plasticity, highlighting an important role of signaling pathways that are also major candidates for contributing to developmental psychiatric disorders. We review here some of these recent advances and discuss the hypothesis that alterations of structural plasticity could represent a common mechanism contributing to the cognitive and functional defects observed in diseases such as intellectual disability, autism spectrum disorders and schizophrenia.

  3. A 'danse macabre': tau and Fyn in STEP with amyloid beta to facilitate induction of synaptic depression and excitotoxicity.

    Science.gov (United States)

    Boehm, Jannic

    2013-06-01

    Alzheimer's disease, with its two most prominent pathological factors amyloid beta and tau protein, can be described as a disease of the synapse. It therefore comes as little surprise that NMDA receptor-related synaptic dysfunction had been thought for several years to underlie the synaptic pathophysiology seen in Alzheimer's disease. In this review I will summarise recent evidence showing that the NMDA receptor links the effects of extracellular amyloid beta with intracellular tau protein. Furthermore, the antagonistic roles of Fyn and STEP in NMDA receptor regulation, synaptic plasticity and induction of synaptic depression will be discussed. PMID:23773061

  4. Spike Pattern Structure Influences Synaptic Efficacy Variability under STDP and Synaptic Homeostasis. II: Spike Shuffling Methods on LIF Networks.

    Science.gov (United States)

    Bi, Zedong; Zhou, Changsong

    2016-01-01

    Synapses may undergo variable changes during plasticity because of the variability of spike patterns such as temporal stochasticity and spatial randomness. Here, we call the variability of synaptic weight changes during plasticity to be efficacy variability. In this paper, we investigate how four aspects of spike pattern statistics (i.e., synchronous firing, burstiness/regularity, heterogeneity of rates and heterogeneity of cross-correlations) influence the efficacy variability under pair-wise additive spike-timing dependent plasticity (STDP) and synaptic homeostasis (the mean strength of plastic synapses into a neuron is bounded), by implementing spike shuffling methods onto spike patterns self-organized by a network of excitatory and inhibitory leaky integrate-and-fire (LIF) neurons. With the increase of the decay time scale of the inhibitory synaptic currents, the LIF network undergoes a transition from asynchronous state to weak synchronous state and then to synchronous bursting state. We first shuffle these spike patterns using a variety of methods, each designed to evidently change a specific pattern statistics; and then investigate the change of efficacy variability of the synapses under STDP and synaptic homeostasis, when the neurons in the network fire according to the spike patterns before and after being treated by a shuffling method. In this way, we can understand how the change of pattern statistics may cause the change of efficacy variability. Our results are consistent with those of our previous study which implements spike-generating models on converging motifs. We also find that burstiness/regularity is important to determine the efficacy variability under asynchronous states, while heterogeneity of cross-correlations is the main factor to cause efficacy variability when the network moves into synchronous bursting states (the states observed in epilepsy). PMID:27555816

  5. Recent advances in understanding synaptic abnormalities in Rett syndrome [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael Johnston

    2015-12-01

    Full Text Available Rett syndrome is an extremely disabling X-linked nervous system disorder that mainly affects girls in early childhood and causes autism-like behavior, severe intellectual disability, seizures, sleep disturbances, autonomic instability, and other disorders due to mutations in the MeCP2 (methyl CpG-binding protein 2 transcription factor. The disorder targets synapses and synaptic plasticity and has been shown to disrupt the balance between glutamate excitatory synapses and GABAergic inhibitory synapses. In fact, it can be argued that Rett syndrome is primarily a disorder of synaptic plasticity and that agents that can correct this imbalance may have beneficial effects on brain development. This review briefly summarizes the link between disrupted synaptic plasticity mechanisms and Rett syndrome and early clinical trials that aim to target these abnormalities to improve the outcome for these severely disabled children.

  6. A Multiscale Bidirectional Coupling Framework

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, Senthil; Kuprat, Andrew P.; Hlastala, Michael P.; Corley, Richard A.; Einstein, Daniel R.

    2011-12-01

    The lung is geometrically articulated across multiple scales from the trachea to the alveoli. A major computational challenge is to tightly link ODEs that describe lower scales to 3D finite element or finite volume models of airway mechanics using iterative communication between scales. In this study, we developed a novel multiscale computational framework for bidirectionally coupling 3D CFD models and systems of lower order ODEs. To validate the coupling framework, a four and eight generation Weibel lung model was constructed. For the coupled CFD-ODE simulations, the lung models were truncated at different generations and a RL circuit represented the truncated portion. The flow characteristics from the coupled models were compared to untruncated full 3D CFD models at peak inhalation and peak exhalation. Results showed that at no time or simulation was the difference in mass flux and/or pressure at a given location between uncoupled and coupled models was greater than 2.43%. The flow characteristics at prime locations for the coupled models showed good agreement to uncoupled models. Remarkably, due to reuse of the Krylov subspace, the cost of the ODE coupling is not much greater than uncoupled full 3D-CFD computations with simple prescribed pressure values at the outlets.

  7. Bidirectional Modulation of Numerical Magnitude.

    Science.gov (United States)

    Arshad, Qadeer; Nigmatullina, Yuliya; Nigmatullin, Ramil; Asavarut, Paladd; Goga, Usman; Khan, Sarah; Sander, Kaija; Siddiqui, Shuaib; Roberts, R E; Cohen Kadosh, Roi; Bronstein, Adolfo M; Malhotra, Paresh A

    2016-05-01

    Numerical cognition is critical for modern life; however, the precise neural mechanisms underpinning numerical magnitude allocation in humans remain obscure. Based upon previous reports demonstrating the close behavioral and neuro-anatomical relationship between number allocation and spatial attention, we hypothesized that these systems would be subject to similar control mechanisms, namely dynamic interhemispheric competition. We employed a physiological paradigm, combining visual and vestibular stimulation, to induce interhemispheric conflict and subsequent unihemispheric inhibition, as confirmed by transcranial direct current stimulation (tDCS). This allowed us to demonstrate the first systematic bidirectional modulation of numerical magnitude toward either higher or lower numbers, independently of either eye movements or spatial attention mediated biases. We incorporated both our findings and those from the most widely accepted theoretical framework for numerical cognition to present a novel unifying computational model that describes how numerical magnitude allocation is subject to dynamic interhemispheric competition. That is, numerical allocation is continually updated in a contextual manner based upon relative magnitude, with the right hemisphere responsible for smaller magnitudes and the left hemisphere for larger magnitudes.

  8. Organic/inorganic hybrid synaptic transistors gated by proton conducting methylcellulose films

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Chang Jin; Wan, Qing, E-mail: wanqing@nju.edu.cn, E-mail: yshi@nju.edu.cn [School of Electronic Science & Engineering, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093 (China); Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); Zhu, Li Qiang [Ningbo Institute of Material Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201 (China); Wan, Xiang; Shi, Yi, E-mail: wanqing@nju.edu.cn, E-mail: yshi@nju.edu.cn [School of Electronic Science & Engineering, and Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093 (China)

    2016-01-25

    The idea of building a brain-inspired cognitive system has been around for several decades. Recently, electric-double-layer transistors gated by ion conducting electrolytes were reported as the promising candidates for synaptic electronics and neuromorphic system. In this letter, indium-zinc-oxide transistors gated by proton conducting methylcellulose electrolyte films were experimentally demonstrated with synaptic plasticity including paired-pulse facilitation and spatiotemporal-correlated dynamic logic. More importantly, a model based on proton-related electric-double-layer modulation and stretched-exponential decay function was proposed, and the theoretical results are in good agreement with the experimentally measured synaptic behaviors.

  9. Organic/inorganic hybrid synaptic transistors gated by proton conducting methylcellulose films

    Science.gov (United States)

    Wan, Chang Jin; Zhu, Li Qiang; Wan, Xiang; Shi, Yi; Wan, Qing

    2016-01-01

    The idea of building a brain-inspired cognitive system has been around for several decades. Recently, electric-double-layer transistors gated by ion conducting electrolytes were reported as the promising candidates for synaptic electronics and neuromorphic system. In this letter, indium-zinc-oxide transistors gated by proton conducting methylcellulose electrolyte films were experimentally demonstrated with synaptic plasticity including paired-pulse facilitation and spatiotemporal-correlated dynamic logic. More importantly, a model based on proton-related electric-double-layer modulation and stretched-exponential decay function was proposed, and the theoretical results are in good agreement with the experimentally measured synaptic behaviors.

  10. Classification: Molecular & Synaptic Mechanisms

    Science.gov (United States)

    Lussier, Marc P.; Gu, Xinglong; Lu, Wei; Roche, Katherine W.

    2014-01-01

    Controlling the density of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at synapses is essential for regulating the strength of excitatory neurotransmission. In particular, the phosphorylation of AMPARs is important for defining both synaptic expression and intracellular routing of receptors. Phosphorylation is a posttranslational modification known to regulate many cellular events and the C-termini of glutamate receptors are important targets. Recently, the first intracellular loop1 region of the GluA1 subunit of AMPARs was reported to regulate synaptic targeting through phosphorylation of S567 by Ca2+/calmodulin-dependent protein kinase II (CaMKII). Intriguingly, the loop1 region of all four AMPAR subunits contains many putative phosphorylation sites (S/T/Y), leaving the possibility that other kinases may regulate AMPAR surface expression via phosphorylation of the loop regions. To explore this hypothesis, we used in vitro phosphorylation assays with a small panel of purified kinases and found that casein kinase 2 (CK2) phosphorylates the GluA1 and GluA2 loop1 regions, but not GluA3 or GluA4. Interestingly, when we reduced the endogenous expression of CK2 using a specific shRNA against the regulatory subunit CK2β, we detected a reduction of GluA1 surface expression, whereas GluA2 was unchanged. Furthermore, we identified S579 of GluA1 as a substrate of CK2, and the expression of GluA1 phospho-deficient mutants in hippocampal neurons displayed reduced surface expression. Therefore, our study identifies CK2 as a regulator of GluA1 surface expression by phosphorylating the intracellular loop1 region. PMID:24712994

  11. The interplay between neuronal activity and actin dynamics mimic the setting of an LTD synaptic tag.

    Science.gov (United States)

    Szabó, Eszter C; Manguinhas, Rita; Fonseca, Rosalina

    2016-09-21

    Persistent forms of plasticity, such as long-term depression (LTD), are dependent on the interplay between activity-dependent synaptic tags and the capture of plasticity-related proteins. We propose that the synaptic tag represents a structural alteration that turns synapses permissive to change. We found that modulation of actin dynamics has different roles in the induction and maintenance of LTD. Inhibition of either actin depolymerisation or polymerization blocks LTD induction whereas only the inhibition of actin depolymerisation blocks LTD maintenance. Interestingly, we found that actin depolymerisation and CaMKII activation are involved in LTD synaptic-tagging and capture. Moreover, inhibition of actin polymerisation mimics the setting of a synaptic tag, in an activity-dependent manner, allowing the expression of LTD in non-stimulated synapses. Suspending synaptic activation also restricts the time window of synaptic capture, which can be restored by inhibiting actin polymerization. Our results support our hypothesis that modulation of the actin cytoskeleton provides an input-specific signal for synaptic protein capture.

  12. Cdk5 Kinase Activity, Caspase-3 Expression and Synaptic Structural Plasticity in Infra-limbic Cortex of Rats with Conditioned Fear%条件性恐惧大鼠边缘下区Cdk5激酶活性、caspase-3表达以及突触结构的变化

    Institute of Scientific and Technical Information of China (English)

    李培培; 张丽丽; 韦美; 李敏

    2011-01-01

    Classical fear conditioning is a behavioral paradigm that is widely used to study the neuronal mechanisms of post-traumatic stress disorder. Previous studies have clearly identified the medial prefrontal cortex as a key brain area for fear memory traces, but the molecules involving are poorly understood. Recently, the neuronal cyclin dependent kinase 5 (Cdk5) has been implicated in both functional and structural plasticity through affecting ion channel conductance, dendritic spine formation. protein expressions and transcriptions in the postsynaptic neurons. Importantly, dysregulation of Cdk5 has been linked to cell apoptosis, which involves perturbation in synaptic function. How the kinase activity, expression of caspase-3 and synaptic structure have changed in infra-limbic cortex (IL) of conditioned fear? The present study is aimed to answer this question by two experiments.Male adult SD rats were randomly divided into fear group and naive group. Conditioned fear model of rats was established by tone paired foot shock. At the 2nd, 4th and 8th days after fear conditioning, the Cdk5 activity,and expressions of P35 or P25 and caspase-3 in IL area were studied by immunoprecipitation and kinase assay,Western blotting and immunnohistochemical assay. Then the change of synaptic structure at the 8th and 22nd days after conditioned fear was observed with electron microscopy. The results of our experiment 1 showed that Cdk5 activity and expressions of P25 and caspase-3 were all higher in fear group than naive group. In experiment 2, the postsynaptic density (PSD) was thinner in fear group than naive group at the 8th and 22nd days after fear conditioning, but the numerical densities of IL synapse was decreased in fear group at the 22nd day after fear conditioning.Our date suggested that at 8th days after conditioned fear established, the expression of P25 and Cdk5 activity in fear group were higher than naive group, which may lead to the change of synaptic structural

  13. Plasticity theory

    CERN Document Server

    Lubliner, Jacob

    2008-01-01

    The aim of Plasticity Theory is to provide a comprehensive introduction to the contemporary state of knowledge in basic plasticity theory and to its applications. It treats several areas not commonly found between the covers of a single book: the physics of plasticity, constitutive theory, dynamic plasticity, large-deformation plasticity, and numerical methods, in addition to a representative survey of problems treated by classical methods, such as elastic-plastic problems, plane plastic flow, and limit analysis; the problem discussed come from areas of interest to mechanical, structural, and

  14. Plasticity and Injury in the Developing Brain

    OpenAIRE

    Johnston, Michael V.; Ishida, Akira; ISHIDA, Wako Nakajima; MATSUSHITA, Hiroko Baber; NISHIMURA, Akira; Tsuji, Masahiro

    2008-01-01

    The child’s brain is more malleable or plastic than that of adults and this accounts for the ability of children to learn new skills quickly or recovery from brain injuries. Several mechanisms contribute to this ability including overproduction and deletion of neurons and synapses, and activity-dependent stabilization of synapses. The molecular mechanisms for activity dependent synaptic plasticity are being discovered and this is leading to a better understanding of the pathogenesis of severa...

  15. Striatal plasticity and basal ganglia circuit function

    OpenAIRE

    Kreitzer, Anatol C.; Malenka, Robert C.

    2008-01-01

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways—distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive m...

  16. Changes in cortical plasticity across the lifespan

    OpenAIRE

    Catarina eFreitas; Jennifer ePerez; Mark eKnobel; Jose Maria eTormos; Oberman, Lindsay M.; Mark eEldaief; Shahid eBashir; Marine eVernet; Cleofé ePeña-Gómez; Alvaro ePascual-Leone

    2011-01-01

    Deterioration of motor and cognitive performance with advancing age is well documented, but its cause remains unknown. Animal studies dating back to the late 1970’s reveal that age-associated neurocognitive changes are linked to age-dependent changes in synaptic plasticity, including alterations of long-term potentiation and depression (LTP and LTD). Non-invasive brain stimulation techniques enable measurement of LTP- and LTD-like mechanisms of plasticity, in vivo, in humans, and may thus p...

  17. SynProt: A Comprehensive Database for Proteins of the Detergent-Resistant Synaptic Junctions Fraction

    Directory of Open Access Journals (Sweden)

    Rainer ePielot

    2012-06-01

    Full Text Available Chemical synapses are highly specialized cell-cell contacts for communication between neurons in the CNS characterized by complex and dynamic protein networks at both synaptic membranes. The cytomatrix at the active zone (CAZ organizes the apparatus for the regulated release of transmitters from the presynapse. At the postsynaptic side, the postsynaptic density constitutes the machinery for detection, integration and transduction of the transmitter signal. Both pre- and postsynaptic protein networks represent the molecular substrates for synaptic plasticity. Their function can be altered both by regulating their composition and by post-translational modification of their components. For a comprehensive understanding of synaptic networks the entire ensemble of synaptic proteins has to be considered. To support this, we established a comprehensive database for synaptic junction proteins (SynProt database primarily based on proteomics data obtained from biochemical preparations of detergent-resistant synaptic junctions. The database currently contains 2,788 non-redundant entries of rat, mouse and some human proteins, which mainly have been manually extracted from twelve proteomic studies and annotated for synaptic subcellular localization. Each dataset is completed with manually added information including protein classifiers as well as automatically retrieved and updated information from public databases (UniProt and PubMed. We intend that the database will be used to support modeling of synaptic protein networks and rational experimental design.

  18. SynProt: A Database for Proteins of Detergent-Resistant Synaptic Protein Preparations

    Science.gov (United States)

    Pielot, Rainer; Smalla, Karl-Heinz; Müller, Anke; Landgraf, Peter; Lehmann, Anne-Christin; Eisenschmidt, Elke; Haus, Utz-Uwe; Weismantel, Robert; Gundelfinger, Eckart D.; Dieterich, Daniela C.

    2012-01-01

    Chemical synapses are highly specialized cell–cell contacts for communication between neurons in the CNS characterized by complex and dynamic protein networks at both synaptic membranes. The cytomatrix at the active zone (CAZ) organizes the apparatus for the regulated release of transmitters from the presynapse. At the postsynaptic side, the postsynaptic density constitutes the machinery for detection, integration, and transduction of the transmitter signal. Both pre- and postsynaptic protein networks represent the molecular substrates for synaptic plasticity. Their function can be altered both by regulating their composition and by post-translational modification of their components. For a comprehensive understanding of synaptic networks the entire ensemble of synaptic proteins has to be considered. To support this, we established a comprehensive database for synaptic junction proteins (SynProt database) primarily based on proteomics data obtained from biochemical preparations of detergent-resistant synaptic junctions. The database currently contains 2,788 non-redundant entries of rat, mouse, and some human proteins, which mainly have been manually extracted from 12 proteomic studies and annotated for synaptic subcellular localization. Each dataset is completed with manually added information including protein classifiers as well as automatically retrieved and updated information from public databases (UniProt and PubMed). We intend that the database will be used to support modeling of synaptic protein networks and rational experimental design. PMID:22737123

  19. Comparative analyses of bidirectional promoters in vertebrates

    Directory of Open Access Journals (Sweden)

    Taylor James

    2008-05-01

    Full Text Available Abstract Background Orthologous genes with deep phylogenetic histories are likely to retain similar regulatory features. In this report we utilize orthology assignments for pairs of genes co-regulated by bidirectional promoters to map the ancestral history of the promoter regions. Results Our mapping of bidirectional promoters from humans to fish shows that many such promoters emerged after the divergence of chickens and fish. Furthermore, annotations of promoters in deep phylogenies enable detection of missing data or assembly problems present in higher vertebrates. The functional importance of bidirectional promoters is indicated by selective pressure to maintain the arrangement of genes regulated by the promoter over long evolutionary time spans. Characteristics unique to bidirectional promoters are further elucidated using a technique for unsupervised classification, known as ESPERR. Conclusion Results of these analyses will aid in our understanding of the evolution of bidirectional promoters, including whether the regulation of two genes evolved as a consequence of their proximity or if function dictated their co-regulation.

  20. Precise Synaptic Efficacy Alignment Suggests Potentiation Dominated Learning.

    Science.gov (United States)

    Hartmann, Christoph; Miner, Daniel C; Triesch, Jochen

    2015-01-01

    Recent evidence suggests that parallel synapses from the same axonal branch onto the same dendritic branch have almost identical strength. It has been proposed that this alignment is only possible through learning rules that integrate activity over long time spans. However, learning mechanisms such as spike-timing-dependent plasticity (STDP) are commonly assumed to be temporally local. Here, we propose that the combination of temporally local STDP and a multiplicative synaptic normalization mechanism is sufficient to explain the alignment of parallel synapses. To address this issue, we introduce three increasingly complex models: First, we model the idealized interaction of STDP and synaptic normalization in a single neuron as a simple stochastic process and derive analytically that the alignment effect can be described by a so-called Kesten process. From this we can derive that synaptic efficacy alignment requires potentiation-dominated learning regimes. We verify these conditions in a single-neuron model with independent spiking activities but more realistic synapses. As expected, we only observe synaptic efficacy alignment for long-term potentiation-biased STDP. Finally, we explore how well the findings transfer to recurrent neural networks where the learning mechanisms interact with the correlated activity of the network. We find that due to the self-reinforcing correlations in recurrent circuits under STDP, alignment occurs for both long-term potentiation- and depression-biased STDP, because the learning will be potentiation dominated in both cases due to the potentiating events induced by correlated activity. This is in line with recent results demonstrating a dominance of potentiation over depression during waking and normalization during sleep. This leads us to predict that individual spine pairs will be more similar after sleep compared to after sleep deprivation. In conclusion, we show that synaptic normalization in conjunction with coordinated

  1. Precise synaptic efficacy alignment suggests potentiation dominated learning

    Directory of Open Access Journals (Sweden)

    Christoph eHartmann

    2016-01-01

    Full Text Available Recent evidence suggests that parallel synapses from the same axonal branch onto the same dendritic branch have almost identical strength. It has been proposed that this alignment is only possible through learning rules that integrate activity over long time spans. However, learning mechanisms such as spike-timing-dependent plasticity (STDP are commonly assumed to be temporally local. Here, we propose that the combination of temporally local STDP and a multiplicative synaptic normalization mechanism is sufficient to explain the alignment of parallel synapses.To address this issue, we introduce three increasingly complex models: First, we model the idealized interaction of STDP and synaptic normalization in a single neuron as a simple stochastic process and derive analytically that the alignment effect can be described by a so-called Kesten process. From this we can derive that synaptic efficacy alignment requires potentiation-dominated learning regimes. We verify these conditions in a single-neuron model with independent spiking activities but more realistic synapses. As expected, we only observe synaptic efficacy alignment for long-term potentiation-biased STDP. Finally, we explore how well the findings transfer to recurrent neural networks where the learning mechanisms interact with the correlated activity of the network. We find that due to the self-reinforcing correlations in recurrent circuits under STDP, alignment occurs for both long-term potentiation- and depression-biased STDP, because the learning will be potentiation dominated in both cases due to the potentiating events induced by correlated activity. This is in line with recent results demonstrating a dominance of potentiation over depression during waking and normalization during sleep. This leads us to predict that individual spine pairs will be more similar in the morning than they are after sleep depriviation.In conclusion, we show that synaptic normalization in conjunction with

  2. Synaptic control of motoneuronal excitability

    DEFF Research Database (Denmark)

    Rekling, J C; Funk, G D; Bayliss, D A;

    2000-01-01

    important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization......, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre- and postsynaptic actions...

  3. S-SCAM/MAGI-2 is an essential synaptic scaffolding molecule for the GluA2-containing maintenance pool of AMPA receptors

    OpenAIRE

    Danielson, Eric; Zhang, Nanyan; Metallo, Jacob; Kaleka, Kanwardeep; Shin, Seung Min; Gerges, Nashaat; Lee, Sang H.

    2012-01-01

    Synaptic plasticity, the cellular basis of learning and memory, involves the dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses. One of the remaining key unanswered aspects of AMPAR trafficking is the mechanism by which synaptic strength is preserved in spite of protein turnover. In particular, the identity of AMPAR scaffolding molecule(s) involved in the maintenance of GluA2-containing AMPARs is completely unknown. Here we report that Synaptic scaffolding molecule (S-SCA...

  4. STUDY ON THE EFFECTS OF BONE MARROW MESENCHYMAL STEM CELLS TRANSPLANTATION ON THE MECHANISM OF SPONTANEOUS AGED DEMENTIA MICE DEGENERATION OF NEURONS AND SYNAPTIC PLASTICITY CHANGES%BMSCs移植对自发性AD鼠神经元及突触变化影响机制的研究

    Institute of Scientific and Technical Information of China (English)

    郝鑫; 宋彬彬; 赵富生; 武庚

    2014-01-01

    Objective:To explore the effects of bone marrow mesenchymal stem cells transplantation on plasticity in spontaneous aged dementia mice degeneration of neurons and synapses.Methods:The sterile healthy bone marrow stromal stem cells were cultured and identified , rats were divided into normal control group , DMEM control group and transplantation of bone marrow stromal stem cells transplantation group.Bone marrow stromal stem cells transplantation group as intravenous transfusion in the PKH 26 tag,with RT-PCR method, morphological detection , electron microscope observation of bone marrow stromal cells transplantation on senile dementia rat neuronal degeneration and outstanding plasticity.Results:Through the RT-PCR method, morphological detection , electron micro-scope , bone marrow stromal stem cell number cell transplantation group , has been added;at the same time , bone marrow stromal stem cells secrete neurotrophic factor , the in vivo micro environment is improved , leading to the formation of micro environment conducive to repair and the neurons were offered the corresponding protections against necnosis .the number of which in the control group was signifi-cantly higher than that of DMEM transplantation , close to the normal control group , neuronal survival cell number.The micro environ-ment is improved, is conducive to the establishment of synaptic connection with surrounding cells effectively .Conclusion:Bone marrow stem cell transplantation has protective effects on spontaneous aged dementia rat neuron degeneration and outstanding plasticity .%目的:探索骨髓基质干细胞移植对自发性老年痴呆鼠神经元变性及突触可塑性变化的影响。方法:无菌将 Wistar大鼠骨髓基质干细胞进行培养及鉴定,实验分为正常对照组、DMEM移植对照组、骨髓基质干细胞移植组。骨髓基质干细胞移植组在PKH26标记后进行尾静脉回输,再用RT-PCR 方法、组织形态检测、电镜观察等方法

  5. Altered hippocampus synaptic function in selenoprotein P deficient mice

    Directory of Open Access Journals (Sweden)

    Peters Melinda M

    2006-09-01

    Full Text Available Abstract Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1 results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/- mice and wild type littermate controls (Sepp1(+/+ fed a high-selenium diet (1 mg Se/kg were used to characterize activity, motor coordination, and anxiety as well as hippocampus-dependent learning and memory. Normal associative learning, but disrupted spatial learning was observed in Sepp1(-/- mice. In addition, severe alterations were observed in synaptic transmission, short-term plasticity and long-term potentiation in hippocampus area CA1 synapses of Sepp1(-/- mice on a 1 mg Se/kg diet and Sepp1(+/+ mice fed a selenium-deficient (0 mg Se/kg diet. Taken together, these data suggest that selenoprotein P is required for normal synaptic function, either through presence of the protein or delivery of required selenium to the CNS.

  6. Molecular Machines Determining the Fate of Endocytosed Synaptic Vesicles in Nerve Terminals

    Science.gov (United States)

    Fassio, Anna; Fadda, Manuela; Benfenati, Fabio

    2016-01-01

    The cycle of a synaptic vesicle (SV) within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions. The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on: (i) the cyclin-dependent kinase-5 (cdk5) and calcineurin (CN) control of the recycling pool of SVs; (ii) the role of small GTPases of the Rab and ADP-ribosylation factor (Arf) families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission. PMID:27242505

  7. MOLECULAR MACHINES DETERMINING THE FATE OF ENDOCYTOSED SYNAPTIC VESICLES IN NERVE TERMINALS

    Directory of Open Access Journals (Sweden)

    Anna eFassio

    2016-05-01

    Full Text Available The cycle of a synaptic vesicle (SV within the nerve terminal is a step-by-step journey with the final goal of ensuring the proper synaptic strength under changing environmental conditions.The SV cycle is a precisely regulated membrane traffic event in cells and, because of this, a plethora of membrane-bound and cytosolic proteins are devoted to assist SVs in each step of the journey. The cycling fate of endocytosed SVs determines both the availability for subsequent rounds of release and the lifetime of SVs in the terminal and is therefore crucial for synaptic function and plasticity. Molecular players that determine the destiny of SVs in nerve terminals after a round of exo-endocytosis are largely unknown. Here we review the functional role in SV fate of phosphorylation/dephosphorylation of SV proteins and of small GTPases acting on membrane trafficking at the synapse, as they are emerging as key molecules in determining the recycling route of SVs within the nerve terminal. In particular, we focus on (i the cyclin-dependent kinase-5 and calcineurin control of the recycling pool of SVs; (ii the role of small GTPases of the Rab and ADP-ribosylation factor (Arf families in defining the route followed by SV in their nerve terminal cycle. These regulatory proteins together with their synaptic regulators and effectors, are molecular nanomachines mediating homeostatic responses in synaptic plasticity and potential targets of drugs modulating the efficiency of synaptic transmission.

  8. Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents.

    Science.gov (United States)

    Shetty, Mahesh Shivarama; Sharma, Mahima; Hui, Neo Sin; Dasgupta, Ananya; Gopinadhan, Suma; Sajikumar, Sreedharan

    2015-01-01

    Synaptic tagging and capture (STC) and cross-tagging are two important mechanisms at cellular level that explain how synapse-specificity and associativity is achieved in neurons within a specific time frame. These long-term plasticity-related processes are the leading candidate models to study the basis of memory formation and persistence at the cellular level. Both STC and cross-tagging involve two serial processes: (1) setting of the synaptic tag as triggered by a specific pattern of stimulation, and (2) synaptic capture, whereby the synaptic tag interacts with newly synthesized plasticity-related proteins (PRPs). Much of the understanding about the concepts of STC and cross-tagging arises from the studies done in CA1 region of the hippocampus and because of the technical complexity many of the laboratories are still unable to study these processes. Experimental conditions for the preparation of hippocampal slices and the recording of stable late-LTP/LTD are extremely important to study synaptic tagging/cross-tagging. This video article describes the experimental procedures to study long-term plasticity processes such as STC and cross-tagging in the CA1 pyramidal neurons using stable, long-term field-potential recordings from acute hippocampal slices of rats. PMID:26381286

  9. Spike timing-dependent plasticity induces complexity in the brain

    OpenAIRE

    Borges, Rafael R.; Borges, Fernando S.; Lameu, Ewandson L.; Batista, Antonio Marcos; Iarosz, Kelly C.; Caldas, Iberê L.; Antonopoulos, Chris G.; Baptista, Murilo S.

    2016-01-01

    To study neuroplasticity, the capacity of neurons and neural networks to change temporarily or permanently their connections and behavior, we investigate the effects of spike timing-dependent plasticity (STDP) on synchronization in Hodgkin-Huxley neural networks. We consider spike timing-dependent plasticity of excitatory and inhibitory synapses according to the known Hebbian rules for synaptic plasticity. With regard to network architecture, initially the network presents an all-to-all topol...

  10. Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission.

    Science.gov (United States)

    Park, Hye Jin; Lee, Seungheon; Jung, Ji Wook; Lee, Young Choon; Choi, Seong-Min; Kim, Dong Hyun

    2016-07-01

    Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. To test behavioral deficits, an object recognition test was conducted in mouse. In this test, ethanol (1 g/kg, i.p.) impaired object recognition memory, but SM (200 mg/kg) prevented this impairment. To evaluate synaptic deficits, NMDA receptor-mediated excitatory postsynaptic potential (EPSP) and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. SM (10 and 100 μg/ml) significantly ameliorated ethanol-induced long-term potentiation and NMDA receptor-mediated EPSP deficits in the hippocampal slices. Therefore, these results suggest that SM prevents ethanol-induced amnesia by protecting the hippocampus from NMDA receptor-mediated synaptic transmission and synaptic plasticity deficits induced by ethanol. PMID:27257009

  11. EFFECTS OF ESTROGEN AND AGING ON THE SYNAPTIC DISTRIBUTION OF PHOSPHORYLATED AKT-IMMUNOREACTIVITY IN THE CA1 REGION OF THE FEMALE RAT HIPPOCAMPUS

    OpenAIRE

    Yildirim, Murat; JANSSEN, WILLIAM G.M.; Lou, W.Y. Wendy; Akama, Keith T.; McEwen, Bruce S.; Milner, Teresa A.; Morrison, John H.

    2010-01-01

    The estrogen 17β-estradiol (E) increases the axospinous synaptic density and plasticity in the hippocampal CA1 region of young female rats but fails to do so in aged female rats. This E stimulus on synaptic plasticity is associated with the phosphorylation-dependent activation of Akt kinase. Our previous findings demonstrated that increased estrogen levels subsequently increase phosphorylated Akt (pAkt)-immunoreactivity (-IR) within the dendritic shafts and spines of pyramidal neurons in youn...

  12. Endocannabinoid-dopamine interactions in striatal synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Brian Neil Mathur

    2012-04-01

    Full Text Available The nigrostriatal dopaminergic system is implicated in action control and learning. A large body of work has focused on the contribution of this system to modulation of the corticostriatal synapse, the predominant synapse type in the striatum. Signaling through the D2 dopamine receptor is necessary for endocannabinoid-mediated depression of corticostriatal glutamate release. Here we review the known details of this mechanism and discuss newly discovered signaling pathways interacting with this system that ultimately exert dynamic control of cortical input to the striatum and striatal output. This topic is timely with respect to Parkinson’s disease given recent data indicating changes in the striatal endocannabinoid system in patients with this disorder.

  13. Regulation of synaptic plasticity in a schizophrenia model

    OpenAIRE

    Gisabella, Barbara; Bolshakov, Vadim Y.; Benes, Francine M.

    2005-01-01

    The pathology of schizophrenia is characterized by increased hippocampal activity at baseline and during auditory hallucinations. Animal-model studies in which the flow of activity to the hippocampus is increased through decreased amygdalar GABAergic inhibition have shown alterations of hippocampal circuitry similar to schizophrenia, but the functional importance of this phenomenon remains unclear. We provide evidence of decreased hippocampal feed-forward and tonic GABA-mediated inhibition in...

  14. HDAC2 Negatively Regulates Memory Formation and Synaptic Plasticity

    OpenAIRE

    Guan, Ji-Song; Giacometti, Emanuela; Dannenberg, Jan-Hermen; Joseph, Nadine; Gao, Jun; DePinho, Ronald A.; Jaenisch, Rudolf; Tsai, Li-Huei; Haggarty, Stephen John; Nieland, Thomas; Ying ZHOU; Wang, Xinyu; Mazitschek, Ralph; Bradner, James Elliott

    2012-01-01

    Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not ...

  15. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    OpenAIRE

    Carolina A. Oliva; Vargas, Jessica Y.; Nibaldo C Inestrosa

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Despite Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and postsynaptic regions, thus ...

  16. Secure Bidirectional Communication Protocol without Quantum Channel

    OpenAIRE

    Zhang, Z. J.; Man, Z. X.

    2004-01-01

    In this letter we propose a theoretical deterministic secure direct bidirectional quantum communication protocol by using swapping quantum entanglement and local unitary operations, in which the quantum channel for photon transmission can be discarded, hence any attack with or without eavesdropping or even the destructive attack without scruple is impossible.

  17. Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

    Directory of Open Access Journals (Sweden)

    Paul H. Sugarbaker

    2012-01-01

    Full Text Available Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement.

  18. Image fusion using bi-directional similarity

    Science.gov (United States)

    Bai, Chunshan; Luo, Xiaoyan

    2015-05-01

    Infrared images are widely used in the practical applications to capture abundant information. However, it is still challenging to enhance the infrared image by the visual image. In this paper, we propose an effective method using bidirectional similarity. In the proposed method, we aim to find an optimal solution from many feasible solutions without introducing intermediate image. We employ some priori constraints to meet the requirements of image fusion which can be detailed to preserve both good characteristics in the infrared image and spatial information in the visual image. In the iterative step, we use the matrix with the square of the difference between images to integrate the image holding most information. We call this matrix the bidirectional similarity distance. By the bidirectional similarity distance, we can get the transitive images. Then, we fuse the images according to the weight. Experimental results show that, compared to the traditional image fusion algorithm, fusion images from bidirectional similarity fusion algorithm have greatly improved in the subjective vision, entropy, structural similarity index measurement. We believe that the proposed scheme can have a wide applications.

  19. Intergenerational Transmission in a Bidirectional Context

    Directory of Open Access Journals (Sweden)

    Jan De Mol

    2013-07-01

    Full Text Available Traditional approaches to the study of parent-child relationships view intergenerational transmission as a top-down phenomenon in which parents transfer their values, beliefs, and practices to their children. Furthermore, the focus of these unidirectional approaches regarding children's internalisation processes is on continuity or the transmission of similar values, beliefs, and practices from parents to children. Analogous unidirectional perspectives have also influenced the domain of family therapy. In this paper a cognitive-bidirectional and dialectical model of dynamics in parent-child relationships is discussed in which the focus is on continual creation of novel meanings and not just reproduction of old ones in the bidirectional transmission processes between parents and children. Parents and children are addressed as full and equally agents in their interdependent relationship, while these relational dynamics are embedded within culture. This cultural context complicates bidirectional transmission influences in the parent-child relationship as both parents and children are influenced by many other contexts. Further, current research in the domain of parent-child relationships and current concepts of intergenerational transmission in family therapy are reviewed from a bidirectional cognitive-dialectical perspective.

  20. Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture

    Institute of Scientific and Technical Information of China (English)

    Akira Oda; Hidekazu Tanaka

    2014-01-01

    The cholinergic system is involved in a broad spectrum of brain function, and its failure has been implicated in Alzheimer’s disease. Acetylcholine transduces signals through muscarinic and nicotinic acetylcholine receptors, both of which inlfuence synaptic plasticity and cognition. However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to per-sistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic acetylcholine receptors activities affect synaptic morphology and density, which result in per-sistent rearrangements of neural connectivity. Further investigations of the relationships between nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous system may help understand the pathogenesis of Alzheimer’s disease.

  1. Super-resolution microscopy of the synaptic active zone

    Directory of Open Access Journals (Sweden)

    Nadine eEhmann

    2015-01-01

    Full Text Available Brain function relies on accurate information transfer at chemical synapses. At the presynaptic active zone (AZ a variety of specialised proteins are assembled to complex architectures, which set the basis for speed, precision and plasticity of synaptic transmission.Calcium (Ca2+ channels are pivotal for the initiation of excitation-secretion coupling and, correspondingly, capture a central position at the AZ. Combining quantitative functional studies with modelling approaches has provided predictions of channel properties, numbers and even positions on the nanometre scale. However, elucidating the nanoscopic organisation of the surrounding protein network requires direct ultrastructural access. Without this information, knowledge of molecular synaptic structure-function relationships remains incomplete. Recently, super-resolution microscopy techniques have begun to enter the neurosciences. These approaches combine high spatial resolution with the molecular specificity of fluorescence microscopy. Here, we discuss how super-resolution microscopy can be used to obtain information on the organisation of AZ proteins.

  2. Super-resolution microscopy of the synaptic active zone.

    Science.gov (United States)

    Ehmann, Nadine; Sauer, Markus; Kittel, Robert J

    2015-01-01

    Brain function relies on accurate information transfer at chemical synapses. At the presynaptic active zone (AZ) a variety of specialized proteins are assembled to complex architectures, which set the basis for speed, precision and plasticity of synaptic transmission. Calcium channels are pivotal for the initiation of excitation-secretion coupling and, correspondingly, capture a central position at the AZ. Combining quantitative functional studies with modeling approaches has provided predictions of channel properties, numbers and even positions on the nanometer scale. However, elucidating the nanoscopic organization of the surrounding protein network requires direct ultrastructural access. Without this information, knowledge of molecular synaptic structure-function relationships remains incomplete. Recently, super-resolution microscopy (SRM) techniques have begun to enter the neurosciences. These approaches combine high spatial resolution with the molecular specificity of fluorescence microscopy. Here, we discuss how SRM can be used to obtain information on the organization of AZ proteins.

  3. Synaptic Bistability Due to Nucleation and Evaporation of Receptor Clusters

    KAUST Repository

    Burlakov, V. M.

    2012-01-10

    We introduce a bistability mechanism for long-term synaptic plasticity based on switching between two metastable states that contain significantly different numbers of synaptic receptors. One state is characterized by a two-dimensional gas of mobile interacting receptors and is stabilized against clustering by a high nucleation barrier. The other state contains a receptor gas in equilibrium with a large cluster of immobile receptors, which is stabilized by the turnover rate of receptors into and out of the synapse. Transitions between the two states can be initiated by either an increase (potentiation) or a decrease (depotentiation) of the net receptor flux into the synapse. This changes the saturation level of the receptor gas and triggers nucleation or evaporation of receptor clusters. © 2012 American Physical Society.

  4. Synaptic molecular imaging in spared and deprived columns of mouse barrel cortex with array tomography.

    Science.gov (United States)

    Weiler, Nicholas C; Collman, Forrest; Vogelstein, Joshua T; Burns, Randal; Smith, Stephen J

    2014-01-01

    A major question in neuroscience is how diverse subsets of synaptic connections in neural circuits are affected by experience dependent plasticity to form the basis for behavioral learning and memory. Differences in protein expression patterns at individual synapses could constitute a key to understanding both synaptic diversity and the effects of plasticity at different synapse populations. Our approach to this question leverages the immunohistochemical multiplexing capability of array tomography (ATomo) and the columnar organization of mouse barrel cortex to create a dataset comprising high resolution volumetric images of spared and deprived cortical whisker barrels stained for over a dozen synaptic molecules each. These dataset has been made available through the Open Connectome Project for interactive online viewing, and may also be downloaded for offline analysis using web, Matlab, and other interfaces. PMID:25977797

  5. Interaction between the glutamate transporter GLT1b and the synaptic PDZ domain protein PICK1

    DEFF Research Database (Denmark)

    Bassan, Merav; Liu, Hongguang; Madsen, Kenneth L;

    2008-01-01

    Synaptic plasticity is implemented by the interaction of glutamate receptors with PDZ domain proteins. Glutamate transporters provide the only known mechanism of clearance of glutamate from excitatory synapses, and GLT1 is the major glutamate transporter. We show here that GLT1 interacts with the......Synaptic plasticity is implemented by the interaction of glutamate receptors with PDZ domain proteins. Glutamate transporters provide the only known mechanism of clearance of glutamate from excitatory synapses, and GLT1 is the major glutamate transporter. We show here that GLT1 interacts...... expressing PICK1 and GLT1b. In addition, expression of GLT1b in COS7 cells changed the distribution of PICK1, bringing it to the surface. GLT1b and PICK1 co-localized with each other and with synaptic markers in hippocampal neurons in culture. Phorbol ester, an activator of protein kinase C (PKC), a known...

  6. Adolescent alcohol exposure: Burden of epigenetic reprogramming, synaptic remodeling, and adult psychopathology

    Directory of Open Access Journals (Sweden)

    Evan J Kyzar

    2016-05-01

    Full Text Available Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can delay these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood.

  7. Effects of electroacupuncture on synaptic plasticity of hippocampal neurons in model rats with Alzheimer disease%电针对阿尔茨海默病模型大鼠海马神经元突触形态可塑性的影响机制

    Institute of Scientific and Technical Information of China (English)

    罗松; 余曙光; 韩婷

    2006-01-01

    (cerebral cortex was exposured at the same site as model rats, and fornix-fimbria was not cut off) and model group were only fixed but treated with nothing. ③ After treatment, ultrastructure in hippocampal CA3 area of rats was observed with transmission electron microscope;synapse numbers and cross-point numbers between synaptic conjunction and test line were counted with stereological technique; stereological parameters, such as numeric density (Nv), area surface (Sv) and average size of synaptic conjunction, which could reflect plastic changes of synaptic form, were calculated at the same time. ④ Differences between every two groups were compared with t test at regular variance and t'test at irregular variance.MAIN OUTCOME MEASURES: Comparisons of numeric density (Nv),surface density (Sv) and average size of synaptic conjunction.RESULTS: A total of 24 old rats were involved in the final analysis with 6 in each group. ① Ultrastructure: Synaptic density of control and sham operation group was higher than that of model group, and average area of synapse was smaller;, synaptic density of electroacupuncture group increased compared with that of model group, and average area of synapse was smaller. ② Numeric density and surface density in hippocampal CA3 area in model and electroacupuncture group were lower than those of control group and sham operation group (P < 0.05). There was no significant difference between sham operation group and control group (P > 0.05), and those of electroacupuncture group were higher than those of model group (P < 0.01). ③ Average size of synaptic conjunction in hippocampal CA3 of model and electroacupuncture group was higher than that of control and sham operation group (P < 0.05). There was no significant difference between sham operation group and control group (P > 0.05), and the value of electroacupuncture group was lower than that of model group (P < 0.01). CONCLUSION: Electrotherapy can repair synaptic form and inhibit

  8. Inlfuence of cefuroxime sodium on synaptic plasticity of parallel ifber-Purkinje cells in young rats%头孢呋辛钠影响幼鼠平行纤维-浦肯野细胞的突触可塑性

    Institute of Scientific and Technical Information of China (English)

    何海燕; 任颖鸽; 李凌; 晋芙莉; 杜永平; 张月萍

    2016-01-01

    目的探讨头孢呋辛钠(CS)对Sprague-Dawley(SD)大鼠小脑浦肯野细胞(PCs)电生理功能的影响。方法将7 d龄(P7)SD大鼠分为早期用药Ⅰ组、Ⅱ组(P7~P14给药)和晚期用药组(P14~P21给药),均腹腔注射CS;以及早期用药对照组和晚期用药对照组,腹腔注射等容积的生理盐水(NS)。每组均10只。早期用药Ⅰ组及早期对照组于P15处死,早期用药Ⅱ组、晚期用药及晚期对照组于P22处死。采用全细胞膜片钳记录法,在小脑脑片上记录PCs的内向电流和动作电位,以及低频刺激平行纤维(PF)诱发的PCs兴奋性突触后电流(EPSC)的长时程抑制(LTD)现象。结果早期用药组和晚期用药组PCs内向电流幅值和动作电位峰值均略大于相应对照组,差异无统计学意义(P>0.05);用药组的EPSC抑制程度均大于对照组(P0.05). All administration groups had a signiifcantly higher degree of EPSC inhibition than the control groups (P<0.01), and the early administration II group had a signiifcantly greater degree of EPSC inhibition than the late administration group (P<0.01).ConclusionsEarly CS exposure after birth affects the synaptic plasticity of PF-PCs in the cerebellum of young rats, which persists after drug withdrawal.

  9. From Synaptic Transmission to Cognition: An Intermediary Role for Dendritic Spines

    Science.gov (United States)

    Gonzalez-Burgos, Ignacio

    2012-01-01

    Dendritic spines are cytoplasmic protrusions that develop directly or indirectly from the filopodia of neurons. Dendritic spines mediate excitatory neurotransmission and they can isolate the electrical activity generated by synaptic impulses, enabling them to translate excitatory afferent information via several types of plastic changes, including…

  10. DREAM (downstream regulatory element antagonist modulator) contributes to synaptic depression and contextual fear memory.

    Science.gov (United States)

    Wu, Long-Jun; Mellström, Britt; Wang, Hansen; Ren, Ming; Domingo, Sofia; Kim, Susan S; Li, Xiang-Yao; Chen, Tao; Naranjo, Jose R; Zhuo, Min

    2010-01-01

    The downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM), we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD) but not long-term potentiation (LTP), was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory. PMID:20205763

  11. DREAM (Downstream Regulatory Element Antagonist Modulator contributes to synaptic depression and contextual fear memory

    Directory of Open Access Journals (Sweden)

    Wu Long-Jun

    2010-01-01

    Full Text Available Abstract The downstream regulatory element antagonist modulator (DREAM, a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM, we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD but not long-term potentiation (LTP, was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory.

  12. Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement

    DEFF Research Database (Denmark)

    Knafo, Shira; Venero, César; Sánchez-Puelles, Cristina;

    2012-01-01

    Cell adhesion molecules and downstream growth factor-dependent signaling are critical for brain development and synaptic plasticity, and they have been linked to cognitive function in adult animals. We have previously developed a mimetic peptide (FGL) from the neural cell adhesion molecule (NCAM)...

  13. Structural plasticity upon learning: regulation and functions.

    Science.gov (United States)

    Caroni, Pico; Donato, Flavio; Muller, Dominique

    2012-07-01

    Recent studies have provided long-sought evidence that behavioural learning involves specific synapse gain and elimination processes, which lead to memory traces that influence behaviour. The connectivity rearrangements are preceded by enhanced synapse turnover, which can be modulated through changes in inhibitory connectivity. Behaviourally related synapse rearrangement events tend to co-occur spatially within short stretches of dendrites, and involve signalling pathways partially overlapping with those controlling the functional plasticity of synapses. The new findings suggest that a mechanistic understanding of learning and memory processes will require monitoring ensembles of synapses in situ and the development of synaptic network models that combine changes in synaptic function and connectivity.

  14. Heterosynaptic plasticity in pyramidal neurons of the hippocampus

    OpenAIRE

    Haslehurst, P.

    2014-01-01

    Homeostatic synaptic plasticity (HSP) is an adjustment of synaptic strength which compensates for chronically altered activity levels in a neuron’s inputs. It is proposed that HSP allows the neuron to retain its ability to discriminate between different inputs in a changing environment. HSP has been demonstrated at several levels: the network, the individual neuron, and the synapse. Synapse-specific HSP involves a paradox: if intense transmission strengthens a synapse, HSP will act in a compe...

  15. SynapticDB, Effective Web-based Management and Sharing of Data from Serial Section Electron Microscopy

    OpenAIRE

    Shi, Bitao; Bourne, Jennifer; Harris, Kristen M.

    2010-01-01

    Serial section electron microscopy (ssEM) is rapidly expanding as a primary tool to investigate synaptic circuitry and plasticity. The ultrastructural images collected through ssEM are content rich and their comprehensive analysis is beyond the capacity of an individual laboratory. Hence, sharing ultrastructural data is becoming crucial to visualize, analyze, and discover the structural basis of synaptic circuitry and function in the brain. We devised a web-based management system called Syna...

  16. SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3-LAR adhesion.

    Science.gov (United States)

    Lie, Eunkyung; Ko, Ji Seung; Choi, Su-Yeon; Roh, Junyeop Daniel; Cho, Yi Sul; Noh, Ran; Kim, Doyoun; Li, Yan; Kang, Hyeyeon; Choi, Tae-Yong; Nam, Jungyong; Mah, Won; Lee, Dongmin; Lee, Seong-Gyu; Kim, Ho Min; Kim, Hyun; Choi, Se-Young; Um, Ji Won; Kang, Myoung-Goo; Bae, Yong Chul; Ko, Jaewon; Kim, Eunjoon

    2016-01-01

    Synaptic adhesion molecules regulate various aspects of synapse development, function and plasticity. These functions mainly involve trans-synaptic interactions and positive regulations, whereas cis-interactions and negative regulation are less understood. Here we report that SALM4, a member of the SALM/Lrfn family of synaptic adhesion molecules, suppresses excitatory synapse development through cis inhibition of SALM3, another SALM family protein with synaptogenic activity. Salm4-mutant (Salm4(-/-)) mice show increased excitatory synapse numbers in the hippocampus. SALM4 cis-interacts with SALM3, inhibits trans-synaptic SALM3 interaction with presynaptic LAR family receptor tyrosine phosphatases and suppresses SALM3-dependent presynaptic differentiation. Importantly, deletion of Salm3 in Salm4(-/-) mice (Salm3(-/-); Salm4(-/-)) normalizes the increased excitatory synapse number. These results suggest that SALM4 negatively regulates excitatory synapses via cis inhibition of the trans-synaptic SALM3-LAR adhesion.

  17. The Enhanced Rise and Delayed Fall of Memory in a Model of Synaptic Integration: Extension to Discrete State Synapses.

    Science.gov (United States)

    Elliott, Terry

    2016-09-01

    Integrate-and-express models of synaptic plasticity propose that synapses may act as low-pass filters, integrating synaptic plasticity induction signals in order to discern trends before expressing synaptic plasticity. We have previously shown that synaptic filtering strongly controls destabilizing fluctuations in developmental models. When applied to palimpsest memory systems that learn new memories by forgetting old ones, we have also shown that with binary-strength synapses, integrative synapses lead to an initial memory signal rise before its fall back to equilibrium. Such an initial rise is in dramatic contrast to nonintegrative synapses, in which the memory signal falls monotonically. We now extend our earlier analysis of palimpsest memories with synaptic filters to consider the more general case of discrete state, multilevel synapses. We derive exact results for the memory signal dynamics and then consider various simplifying approximations. We show that multilevel synapses enhance the initial rise in the memory signal and then delay its subsequent fall by inducing a plateau-like region in the memory signal. Such dynamics significantly increase memory lifetimes, defined by a signal-to-noise ratio (SNR). We derive expressions for optimal choices of synaptic parameters (filter size, number of strength states, number of synapses) that maximize SNR memory lifetimes. However, we find that with memory lifetimes defined via mean-first-passage times, such optimality conditions do not exist, suggesting that optimality may be an artifact of SNRs. PMID:27391686

  18. Human synapses show a wide temporal window for spike-timing-dependent plasticity

    Directory of Open Access Journals (Sweden)

    Guilherme T Silva

    2010-07-01

    Full Text Available Throughout our lifetime, activity-dependent changes in neuronal connection strength enable the brain to refine neural circuits and learn based on experience. Synapses can bi-directionally alter strength and the magnitude and sign depend on the millisecond timing of presynaptic and postsynaptic action potential firing. Recent findings on laboratory animals have shown that neurons can show a variety of temporal windows for spike-timing-dependent plasticity (STDP. It is unknown what synaptic learning rules exist in human synapses and whether similar temporal windows for STDP at synapses hold true for the human brain. Here, we directly tested in human slices cut from hippocampal tissue removed for surgical treatment of deeper brain structures in drug-resistant epilepsy patients, whether adult human synapses can change strength in response to millisecond timing of pre- and postsynaptic firing. We find that adult human hippocampal synapses can alter synapse strength in response to timed pre- and postsynaptic activity. In contrast to rodent hippocampal synapses, the sign of plasticity does not sharply switch around 0 millisecond timing. Instead, both positive timing intervals, in which presynaptic firing preceded the postsynaptic action potential, and negative timing intervals, in which postsynaptic firing preceded presynaptic activity down to -80 ms, increase synapse strength (tLTP. Negative timing intervals between -80 to -130 ms induce a lasting reduction of synapse strength (tLTD. Thus, similar to rodent synapses, adult human synapses can show spike-timing-dependent changes in strength. The timing rules of STDP in human hippocampus, however, seem to differ from rodent hippocampus, and suggest a less strict interpretation of Hebb’s predictions.

  19. In vivo neuron-wide analysis of synaptic vesicle precursor trafficking.

    Science.gov (United States)

    Maeder, Celine I; San-Miguel, Adriana; Wu, Emily Ye; Lu, Hang; Shen, Kang

    2014-03-01

    During synapse development, synaptic proteins must be targeted to sites of presynaptic release. Directed transport as well as local sequestration of synaptic vesicle precursors (SVPs), membranous organelles containing many synaptic proteins, might contribute to this process. Using neuron-wide time-lapse microscopy, we studied SVP dynamics in the DA9 motor neuron in Caenorhabditis elegans. SVP transport was highly dynamic and bi-directional throughout the entire neuron, including the dendrite. While SVP trafficking was anterogradely biased in axonal segments prior to the synaptic domain, directionality of SVP movement was stochastic in the dendrite and distal axon. Furthermore, frequency of movement and speed were variable between different compartments. These data provide evidence that SVP transport is differentially regulated in distinct neuronal domains. It also suggests that polarized SVP transport in concert with local vesicle capturing is necessary for accurate presynapse formation and maintenance. SVP trafficking analysis of two hypomorphs for UNC-104/KIF1A in combination with mathematical modeling identified directionality of movement, entry of SVPs into the axon as well as axonal speeds as the important determinants of steady-state SVP distributions. Furthermore, detailed dissection of speed distributions for wild-type and unc-104/kif1a mutant animals revealed an unexpected role for UNC-104/KIF1A in dendritic SVP trafficking.

  20. Design and Implementation of Bidirectional Dijkstra Algorithm

    Institute of Scientific and Technical Information of China (English)

    付梦印; 李杰; 周培德

    2003-01-01

    Bidirectional Dijkstra algorithm whose time complexity is (1)/(8)O(n2) is proposed. The theory foundation is that the classical Dijkstra algorithm has not any directional feature during searching the shortest path. The algorithm takes advantage of the adjacent link and the mechanism of bidirectional search, that is, the algorithm processes the positive search from start point to destination point and the negative search from destination point to start point at the same time. Finally, combining with the practical application of route-planning algorithm in embedded real-time vehicle navigation system (ERTVNS), one example of its practical applications is given, analysis in theory and the experimental results show that compared with the Dijkstra algorithm, the new algorithm can reduce time complexity, and guarantee the searching precision, it satisfies the needs of ERTVNS.