The Experts below are selected from a list of 7536 Experts worldwide ranked by ideXlab platform

Jianghong Ye - One of the best experts on this subject based on the ideXlab platform.

Samuel Schacher - One of the best experts on this subject based on the ideXlab platform.

  • selective erasure of distinct forms of long term synaptic plasticity underlying different forms of memory in the same Postsynaptic Neuron
    Current Biology, 2017
    Co-Authors: Jiangyuan Hu, Larissa Ferguson, Kerry Adler, Carole A Farah, Margaret H Hastings, Wayne S Sossin, Samuel Schacher
    Abstract:

    Summary Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same Postsynaptic Neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the Postsynaptic Neuron. A dominant-negative (dn) atypical PKM selectively reversed associative LTF, while a dn classical PKM selectively reversed non-associative LTF. Although both PKMs are formed from calpain-mediated cleavage of protein kinase C (PKC) isoforms, each form of LTF is sensitive to a distinct dn calpain expressed in the Postsynaptic Neuron. Associative LTF is blocked by dn classical calpain, whereas non-associative LTF is blocked by dn small optic lobe (SOL) calpain. Interfering with a putative synaptic tag, the adaptor protein KIBRA, which protects the atypical PKM from degradation, selectively erases associative LTF. Thus, the activity of distinct PRPs and tags in a Postsynaptic Neuron contribute to the maintenance of different forms of synaptic plasticity at separate inputs, allowing for selective reversal of synaptic plasticity and providing a cellular basis for developing therapeutic strategies for selectively reversing maladaptive memories.

  • cjun and creb2 in the Postsynaptic Neuron contribute to persistent long term facilitation at a behaviorally relevant synapse
    The Journal of Neuroscience, 2015
    Co-Authors: Jiangyuan Hu, Amir Levine, Yingju Sung, Samuel Schacher
    Abstract:

    Basic region leucine zipper (bZIP) transcription factors regulate gene expression critical for long-term synaptic plasticity or Neuronal excitability contributing to learning and memory. At sensorimotor synapses of Aplysia, changes in activation or expression of CREB1 and CREB2 in sensory Neurons are required for long-term synaptic plasticity. However, it is unknown whether concomitant stimulus-induced changes in expression and activation of bZIP transcription factors in the Postsynaptic motor Neuron also contribute to persistent long-term facilitation (P-LTF). We overexpressed various forms of CREB1, CREB2, or cJun in the Postsynaptic motor Neuron L7 in cell culture to examine whether these factors contribute to P-LTF. P-LTF is evoked by 2 consecutive days of 5-HT applications (2 5-HT), while a transient form of LTF is produced by 1 day of 5-HT applications (1 5-HT). Significant increases in the expression of both cJun and CREB2 mRNA in L7 accompany P-LTF. Overexpressing each bZIP factor in L7 did not alter basal synapse strength, while coexpressing cJun and CREB2 in L7 evoked persistent increases in basal synapse strength. In contrast, overexpressing cJun and CREB2 in sensory Neurons evoked persistent decreases in basal synapse strength. Overexpressing wild-type cJun or CREB2, but not CREB1, in L7 can replace the second day of 5-HT applications in producing P-LTF. Reducing cJun activity in L7 blocked P-LTF evoked by 2 5-HT. These results suggest that expression and activation of different bZIP factors in both presynaptic and Postsynaptic Neurons contribute to persistent change in synapse strength including stimulus-dependent long-term synaptic plasticity.

  • aplysia cell adhesion molecule and a novel protein kinase c activity in the Postsynaptic Neuron are required for presynaptic growth and initial formation of specific synapses
    The Journal of Neuroscience, 2010
    Co-Authors: Jiangyuan Hu, Wayne S Sossin, Yang Chen, Joanna K Bougie, Samuel Schacher
    Abstract:

    To explore the role of both Aplysia cell adhesion molecule (ApCAM) and activity of specific protein kinase C (PKC) isoforms in the initial formation of sensory Neuron synapses with specific Postsynaptic targets (L7 but not L11), we examined presynaptic growth, initial synapse formation, and the expression of the presynaptic neuropeptide sensorin following cell-specific reduction of ApCAM or of a novel PKC activity. Synapse formation between sensory Neurons and L7 begins by 3 h after plating and is accompanied by a rapid accumulation of a novel PKC to sites of synaptic interaction. Reducing ApCAM expression specifically from the surface of L7 blocks presynaptic growth and initial synapse formation, target-induced increase of sensorin in sensory Neuron cell bodies and the rapid accumulation of the novel PKC to sites of interaction. Selective blockade of the novel PKC activity in L7, but not in sensory Neurons, with injection of a dominant negative construct that interferes with the novel PKC activity, produces the same actions as downregulating ApCAM; blockade of presynaptic growth and initial synapse formation, and the target-induced increase of sensorin in sensory Neuron cell bodies. The results indicate that signals initiated by Postsynaptic cell adhesion molecule ApCAM coupled with the activation of a novel PKC in the appropriate Postsynaptic Neuron produce the retrograde signals required for presynaptic growth associated with initial synapse formation, and the target-induced expression of a presynaptic neuropeptide critical for synapse maturation.

  • changes in functional glutamate receptors on a Postsynaptic Neuron accompany formation and maturation of an identified synapse
    Journal of Neurobiology, 1999
    Co-Authors: Parker Conrad, Fang Wu, Samuel Schacher
    Abstract:

    : N-Methyl-D-aspartate (NMDA)-type glutamate receptors play important roles at developing synapses and in activity-dependent synaptic plasticity. Recent studies in Aplysia suggest that NMDA-like receptors may contribute to some forms of plasticity of sensorimotor synapses accompanying associative learning. We examined at various times after plating Neurons in culture the contribution of NMDA- and alpha-amino-3 hydroxy-5 methyl-4 isoxazole proprionic acid (AMPA)-like glutamate receptors to responses evoked in motor cell L7 either by action potentials in sensory Neurons (SNs) or by focal applications of glutamate. We found that (D,L)-2-amino-5-phosphopentoic acid-sensitive receptors contributed significantly to Postsynaptic responses in 1-day cultures but contributed little in the same cultures on day 4. By contrast, Postsynaptic responses on day 4 increased significantly in amplitude by the addition of functional 6-cyano-7 nitroquinoxaline-2,3-dione- or 1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine hydrochloride-sensitive receptors. Receptors with NMDA-like properties are detected on day 1 only at sites on L7 apposed to SN varicosities, and are not detected on L7 cultured alone. The results indicate that changes in expression and distribution of functional receptors on L7 accompany the formation and maturation of SN synapses. Signals from the SN appear to trigger expression and clustering of functional NMDA-like receptors at sites contacted by presynaptic structures capable of transmitter release. With time, functional AMPA-like receptors are added to these sites enhancing synaptic efficacy. The results are consistent with the idea that the expression and sequential clustering of NMDA- and AMPA-type receptors may be essential for the formation and maturation of central synapses.

Chunyu Deng - One of the best experts on this subject based on the ideXlab platform.

Jon Timmis - One of the best experts on this subject based on the ideXlab platform.

  • Exploring Self-Repair in a Coupled Spiking Astrocyte Neural Network
    IEEE Transactions on Neural Networks and Learning Systems, 2019
    Co-Authors: Liam J. Mcdaid, Anju P. Johnson, Alan G. Millard, Shvan Karim, Andy M. Tyrrell, Jim Harkin, David M. Halliday, James Hilder, Jon Timmis
    Abstract:

    It is now known that astrocytes modulate the activity at the tripartite synapses where indirect signaling via the retrograde messengers, endocannabinoids, leads to a localized self-repairing capability. In this paper, a self-repairing spiking astrocyte neural network (SANN) is proposed to demonstrate a distributed self-repairing capability at the network level. The SANN uses a novel learning rule that combines the spike-timing-dependent plasticity (STDP) and Bienenstock, Cooper, and Munro (BCM) learning rules (hereafter referred to as the BSTDP rule). In this learning rule, the synaptic weight potentiation is not only driven by the temporal difference between the presynaptic and Postsynaptic Neuron firing times but also by the Postsynaptic Neuron activity. We will show in this paper that the BSTDP modulates the height of the plasticity window to establish an input-output mapping (in the learning phase) and also maintains this mapping (via self-repair) if synaptic pathways become dysfunctional. It is the functional dependence of Postsynaptic Neuron firing activity on the height of the plasticity window that underpins how the proposed SANN self-repairs on the fly. The SANN also uses the coupling between the tripartite synapses and $\gamma $ -GABAergic interNeurons. This interaction gives rise to a presynaptic Neuron frequency filtering capability that serves to route information, represented as spike trains, to different Neurons in the subsequent layers of the SANN. The proposed SANN follows a feedforward architecture with multiple interNeuron pathways and astrocytes modulate synaptic activity at the hidden and output Neuronal layers. The self-repairing capability will be demonstrated in a robotic obstacle avoidance application, and the simulation results will show that the SANN can maintain learned maneuvers at synaptic fault densities of up to 80% regardless of the fault locations.

  • Fault-Tolerant Learning in Spiking Astrocyte-Neural Networks on FPGAs
    2018 31st International Conference on VLSI Design and 2018 17th International Conference on Embedded Systems (VLSID), 2018
    Co-Authors: Anju P. Johnson, Alan G. Millard, Shvan Karim, Andy M. Tyrrell, Jim Harkin, Jon Timmis, Liam Mcdaid, David M. Halliday
    Abstract:

    The paper presents a neuromorphic system implemented on a Field Programmable Gate Array (FPGA) device establishing fault tolerance using a learning method, which is a combination of the Spike-Timing-Dependent Plasticity (STDP) and Bienenstock, Cooper, and Munro (BCM) learning rules. The rule modulates the synaptic plasticity level by shifting the plasticity window, associated with STDP, up/down the vertical axis as a function of Postsynaptic neural activity. Specifically when Neurons are inactive, either early on in the normal learning phase or when a fault occurs, the window is shifted up the vertical axis (open), leading to an increase in firing rate of the Postsynaptic Neuron. As learning progresses, the plasticity window moves down the vertical axis until the desired Postsynaptic Neuron firing rate is established. Experimental results are presented to show the effectiveness of the proposed approach in establishing fault tolerance. The system can maintain the network performance with at least one nonfaulty synapse. Finally, we discuss a robotic application utilizing the proposed architecture.

Jiangyuan Hu - One of the best experts on this subject based on the ideXlab platform.

  • selective erasure of distinct forms of long term synaptic plasticity underlying different forms of memory in the same Postsynaptic Neuron
    Current Biology, 2017
    Co-Authors: Jiangyuan Hu, Larissa Ferguson, Kerry Adler, Carole A Farah, Margaret H Hastings, Wayne S Sossin, Samuel Schacher
    Abstract:

    Summary Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same Postsynaptic Neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the Postsynaptic Neuron. A dominant-negative (dn) atypical PKM selectively reversed associative LTF, while a dn classical PKM selectively reversed non-associative LTF. Although both PKMs are formed from calpain-mediated cleavage of protein kinase C (PKC) isoforms, each form of LTF is sensitive to a distinct dn calpain expressed in the Postsynaptic Neuron. Associative LTF is blocked by dn classical calpain, whereas non-associative LTF is blocked by dn small optic lobe (SOL) calpain. Interfering with a putative synaptic tag, the adaptor protein KIBRA, which protects the atypical PKM from degradation, selectively erases associative LTF. Thus, the activity of distinct PRPs and tags in a Postsynaptic Neuron contribute to the maintenance of different forms of synaptic plasticity at separate inputs, allowing for selective reversal of synaptic plasticity and providing a cellular basis for developing therapeutic strategies for selectively reversing maladaptive memories.

  • cjun and creb2 in the Postsynaptic Neuron contribute to persistent long term facilitation at a behaviorally relevant synapse
    The Journal of Neuroscience, 2015
    Co-Authors: Jiangyuan Hu, Amir Levine, Yingju Sung, Samuel Schacher
    Abstract:

    Basic region leucine zipper (bZIP) transcription factors regulate gene expression critical for long-term synaptic plasticity or Neuronal excitability contributing to learning and memory. At sensorimotor synapses of Aplysia, changes in activation or expression of CREB1 and CREB2 in sensory Neurons are required for long-term synaptic plasticity. However, it is unknown whether concomitant stimulus-induced changes in expression and activation of bZIP transcription factors in the Postsynaptic motor Neuron also contribute to persistent long-term facilitation (P-LTF). We overexpressed various forms of CREB1, CREB2, or cJun in the Postsynaptic motor Neuron L7 in cell culture to examine whether these factors contribute to P-LTF. P-LTF is evoked by 2 consecutive days of 5-HT applications (2 5-HT), while a transient form of LTF is produced by 1 day of 5-HT applications (1 5-HT). Significant increases in the expression of both cJun and CREB2 mRNA in L7 accompany P-LTF. Overexpressing each bZIP factor in L7 did not alter basal synapse strength, while coexpressing cJun and CREB2 in L7 evoked persistent increases in basal synapse strength. In contrast, overexpressing cJun and CREB2 in sensory Neurons evoked persistent decreases in basal synapse strength. Overexpressing wild-type cJun or CREB2, but not CREB1, in L7 can replace the second day of 5-HT applications in producing P-LTF. Reducing cJun activity in L7 blocked P-LTF evoked by 2 5-HT. These results suggest that expression and activation of different bZIP factors in both presynaptic and Postsynaptic Neurons contribute to persistent change in synapse strength including stimulus-dependent long-term synaptic plasticity.

  • aplysia cell adhesion molecule and a novel protein kinase c activity in the Postsynaptic Neuron are required for presynaptic growth and initial formation of specific synapses
    The Journal of Neuroscience, 2010
    Co-Authors: Jiangyuan Hu, Wayne S Sossin, Yang Chen, Joanna K Bougie, Samuel Schacher
    Abstract:

    To explore the role of both Aplysia cell adhesion molecule (ApCAM) and activity of specific protein kinase C (PKC) isoforms in the initial formation of sensory Neuron synapses with specific Postsynaptic targets (L7 but not L11), we examined presynaptic growth, initial synapse formation, and the expression of the presynaptic neuropeptide sensorin following cell-specific reduction of ApCAM or of a novel PKC activity. Synapse formation between sensory Neurons and L7 begins by 3 h after plating and is accompanied by a rapid accumulation of a novel PKC to sites of synaptic interaction. Reducing ApCAM expression specifically from the surface of L7 blocks presynaptic growth and initial synapse formation, target-induced increase of sensorin in sensory Neuron cell bodies and the rapid accumulation of the novel PKC to sites of interaction. Selective blockade of the novel PKC activity in L7, but not in sensory Neurons, with injection of a dominant negative construct that interferes with the novel PKC activity, produces the same actions as downregulating ApCAM; blockade of presynaptic growth and initial synapse formation, and the target-induced increase of sensorin in sensory Neuron cell bodies. The results indicate that signals initiated by Postsynaptic cell adhesion molecule ApCAM coupled with the activation of a novel PKC in the appropriate Postsynaptic Neuron produce the retrograde signals required for presynaptic growth associated with initial synapse formation, and the target-induced expression of a presynaptic neuropeptide critical for synapse maturation.