The Experts below are selected from a list of 789 Experts worldwide ranked by ideXlab platform
Eric R Kandel - One of the best experts on this subject based on the ideXlab platform.
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Gene expression profiling of facilitated L-LTP in VP16-CREB mice reveals that BDNF is critical for the maintenance of LTP and its synaptic capture
Neuron, 2005Co-Authors: Angel Barco, Juan M Alarcon, Alexei Morozov, Susan L. Patterson, Petra Gromova, Manuel Mata-roig, Eric R KandelAbstract:Expression of VP16-CREB, a constitutively active form of CREB, in hippocampal neurons of the CA1 region lowers the threshold for eliciting the late, persistent phase of long-term potentiation (L-LTP) in the Schaffer Collateral Pathway. This VP16-CREB-mediated L-LTP differs from the conventional late phase of LTP in not being dependent on new transcription. This finding suggests that in the transgenic mice the mRNA transcript(s) encoding the protein(s) necessary for this form of L-LTP might already be present in CA1 neurons in the basal condition. We used high-density oligonucleotide arrays to identify the mRNAs differentially expressed in the hippocampus of transgenic and wild-type mice. We then explored the contribution of the most prominent candidate genes revealed by our screening, namely prodynorphin, BDNF, and MHC class I molecules, to the facilitated LTP of VP16-CREB mice. We found that the overexpression of brain-derived neurotrophic factor accounts for an important component of this phenotype.
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Rap1 couples cAMP signaling to a distinct pool of p42/44MAPK regulating excitability, synaptic plasticity, learning, and memory.
Neuron, 2003Co-Authors: Alexei Morozov, Isabel A. Muzzio, Rusiko Bourtchouladze, Niels Van-strien, Kyle A.b. Lapidus, Deqi Yin, Danny G. Winder, J. Paige Adams, J. David Sweatt, Eric R KandelAbstract:Learning-induced synaptic plasticity commonly involves the interaction between cAMP and p42/44MAPK. To investigate the role of Rap1 as a potential signaling molecule coupling cAMP and p42/44MAPK, we expressed an interfering Rap1 mutant (iRap1) in the mouse forebrain. This expression selectively decreased basal phosphorylation of a membrane-associated pool of p42/44MAPK, impaired cAMP-dependent LTP in the hippocampal Schaffer Collateral Pathway induced by either forskolin or theta frequency stimulation, decreased complex spike firing, and reduced the p42/44MAPK-mediated phosphorylation of the A-type potassium channel Kv4.2. These changes correlated with impaired spatial memory and context discrimination. These results indicate that Rap1 couples cAMP signaling to a selective membrane-associated pool of p42/44MAPK to control excitability of pyramidal cells, the early and late phases of LTP, and the storage of spatial memory.
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expression of constitutively active creb protein facilitates the late phase of long term potentiation by enhancing synaptic capture
Cell, 2002Co-Authors: Angel Barco, Juan M Alarcon, Eric R KandelAbstract:Restricted and regulated expression in mice of VP16-CREB, a constitutively active form of CREB, in hippocampal CA1 neurons lowers the threshold for eliciting a persistent late phase of long-term potentiation (L-LTP) in the Schaffer Collateral Pathway. This L-LTP has unusual properties in that its induction is not dependent on transcription. Pharmacological and two-Pathway experiments suggest a model in which VP16-CREB activates the transcription of CRE-driven genes and leads to a cell-wide distribution of proteins that prime the synapses for subsequent synapse-specific capture of L-LTP by a weak stimulus. Our analysis indicates that synaptic capture of CRE-driven gene products may be sufficient for consolidation of LTP and provides insight into the molecular mechanisms of synaptic tagging and synapse-specific potentiation.
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d1 d5 receptor agonists induce a protein synthesis dependent late potentiation in the ca1 region of the hippocampus
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Yan You Huang, Eric R KandelAbstract:Abstract Agonists of the dopamine D1/D5 receptors that are positively coupled to adenylyl cyclase specifically induce a slowly developing long-lasting potentiation of the field excitatory postsynaptic potential in the CA1 region of the hippocampus that lasts for > 6 hr. This potentiation is blocked by the specific D1/D5 receptor antagonist SCH 23390 and is occluded by the potentiation induced by cAMP agonists. An agonist of the D2 receptor, which is negatively coupled to adenylyl cyclase through G alpha i, did not induce potentiation. Although this slow D1/D5 agonist-induced potentiation is partially independent of N-methyl-D-aspartate receptors, it seems to share some steps with and is occluded by the late phase of long-term potentiation (LTP) produced by three repeated trains of nerve stimuli applied to the Schaffer Collateral Pathway. Similarly, the D1/D5 antagonist SCH 23390 attenuates the late phase of the LTP induced by repeated trains, and the D1/D5 agonist-induced potentiation is blocked by the protein synthesis inhibitor anisomycin. These results suggest that the D1/D5 receptor may be involved in the late, protein synthesis-dependent component of LTP in the hippocampal CA1 region, either as an ancillary component or as a mediator directly contributing to the late phase.
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D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus.
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Yan You Huang, Eric R KandelAbstract:Agonists of the dopamine D1/D5 receptors that are positively coupled to adenylyl cyclase specifically induce a slowly developing long-lasting potentiation of the field excitatory postsynaptic potential in the CA1 region of the hippocampus that lasts for > 6 hr. This potentiation is blocked by the specific D1/D5 receptor antagonist SCH 23390 and is occluded by the potentiation induced by cAMP agonists. An agonist of the D2 receptor, which is negatively coupled to adenylyl cyclase through G alpha i, did not induce potentiation. Although this slow D1/D5 agonist-induced potentiation is partially independent of N-methyl-D-aspartate receptors, it seems to share some steps with and is occluded by the late phase of long-term potentiation (LTP) produced by three repeated trains of nerve stimuli applied to the Schaffer Collateral Pathway. Similarly, the D1/D5 antagonist SCH 23390 attenuates the late phase of the LTP induced by repeated trains, and the D1/D5 agonist-induced potentiation is blocked by the protein synthesis inhibitor anisomycin. These results suggest that the D1/D5 receptor may be involved in the late, protein synthesis-dependent component of LTP in the hippocampal CA1 region, either as an ancillary component or as a mediator directly contributing to the late phase.
Sadao Shiosaka - One of the best experts on this subject based on the ideXlab platform.
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Diversity of neuropsin (KLK8)-dependent synaptic associativity in the hippocampal pyramidal neuron.
The Journal of physiology, 2011Co-Authors: Yasuyuki Ishikawa, Hideki Tamura, Sadao ShiosakaAbstract:Hippocampal early (E-) long-term potentiation (LTP) and long-term depression (LTD) elicited by a weak stimulus normally fades within 90 min. Late (L-) LTP and LTD elicited by strong stimuli continue for >180 min and require new protein synthesis to persist. If a strong tetanus is applied once to synaptic inputs, even a weak tetanus applied to another synaptic input can evoke persistent LTP. A synaptic tag is hypothesized to enable the capture of newly synthesized synaptic molecules. This process, referred to as synaptic tagging, is found between not only the same processes (i.e. E- and L-LTP; E- and L-LTD) but also between different processes (i.e. E-LTP and L-LTD; E-LTD and L-LTP) induced at two independent synaptic inputs (cross-tagging). However, the mechanisms of synaptic tag setting remain unclear. In our previous study, we found that synaptic associativity in the hippocampal Schaffer Collateral Pathway depended on neuropsin (kallikrein-related peptidase 8 or KLK8), a plasticity-related extracellular protease. In the present study, we investigated how neuropsin participates in synaptic tagging and cross-tagging. We report that neuropsin is involved in synaptic tagging during LTP at basal and apical dendritic inputs. Moreover, neuropsin is involved in synaptic tagging and cross-tagging during LTP at apical dendritic inputs via integrin β1 and calcium/calmodulin-dependent protein kinase II signalling. Thus, neuropsin is a candidate molecule for the LTP-specific tag setting and regulates the transformation of E- to L-LTP during both synaptic tagging and cross-tagging.
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Neuropsin--a possible modulator of synaptic plasticity.
Journal of chemical neuroanatomy, 2011Co-Authors: Sadao Shiosaka, Yasuyuki IshikawaAbstract:Accumulating evidence has suggested pivotal roles for neural proteases in development, maturation, aging, and cognitive functions. Among such proteases, neuropsin, a kallikrein gene-related (KLK) endoprotease, appears to have a significant plasticity function that has been analyzed primarily in the hippocampal Schaffer-Collateral Pathway. In this article, after reviewing the general features of neuropsin, its role in Schaffer-Collateral synaptic plasticity is discussed in some detail. Enzymatically active neuropsin is necessary to establish the early phase of long-term potentiation (LTP). This type of LTP, which can be elicited by rather weak tetanic stimulation, is significant in synaptic late association between two independent hippocampal synapses. Neuropsin deficiency completely impaired the early phase of LTP, leading to the absence of late associativity. Associations between early and persistent-LTP synapses may be related to mammalian working memory and consequently integration in learning and memory.
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Neuropsin (KLK8)-Dependent and -Independent Synaptic Tagging in the Schaffer-Collateral Pathway of Mouse Hippocampus
Journal of Neuroscience, 2008Co-Authors: Yasuyuki Ishikawa, Yoichiro Horii, Hideki Tamura, Sadao ShiosakaAbstract:Hippocampal early long-term potentiation (LTP) elicited by a weak (one or two) tetanic stimulus normally fades away within 90 min. Late LTP elicited by strong (four) stimuli lasts >180 min and requires new protein synthesis to persist. If a strong tetanus is injected once into a synapse, even a weak tetanus injected into another synapse can evoke persistent LTP. It was hypothesized that a synaptic tag enables capture of newly synthesized synaptic molecules. Here, we found two synaptic capture mechanisms for a weakly stimulated synapse to acquire persistency (i.e., neuropsin dependent and independent). The single tetanus evokes a neuropsin-dependent form that follows downstream signaling into integrin/actin signal and L-type voltage-dependent Ca2+ channel (LVDCC) Pathway. Additionally, a neuropsin-independent form of synaptic capture is evoked by a stronger (two) tetanus than the former. Both forms converging on LVDCC might serve different associative memories depending on their input strength. Our study strongly supports the hypothesis of synaptic tagging and demonstrates that neuropsin-dependent late associativity is particularly important in nonstressful associative memory.
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Increased anxiety-like behavior in neuropsin (kallikrein-related peptidase 8) gene-deficient mice.
Behavioral neuroscience, 2008Co-Authors: Yoichiro Horii, Nobuyuki Yamasaki, Tsuyoshi Miyakawa, Sadao ShiosakaAbstract:Neuropsin (kallikrein-related peptidase 8) is concentrated in the hippocampus, amygdala, olfactory bulb, and prefrontal cortex. Earlier studies showed that protease deficiency causes a significant impairment of early-phase long-term potentiation in the Schaffer Collateral Pathway and hippocampus-dependent memory in the Y maze and Morris water maze (Z. Chen et al., 1995; A. Hirata et al., 2001; H. Tamura et al., 2006). In addition to neuropsin's participation in the hippocampal memory, amygdalar and cortical localization of the gene suggests extrahippocampal behavioral function, and the authors therefore examined neuropsin-deficient mice, including tests of sensory motor reflex, open field, light-dark transition, Rota-Rod, elevated plus-maze, hot plate, startle response-prepulse inhibition, Porsolt forced swim, Barnes maze, eight-arm radial maze, and contextual and cued fear conditioning tests. Here, the authors found increased anxiety in neuropsin-deficient mice, suggesting the involvement of this protease in emotional responses.
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An implantable and fully integrated complementary metal–oxide semiconductor device for in vivo neural imaging and electrical interfacing with the mouse hippocampus
Sensors and Actuators A-physical, 2007Co-Authors: Hideki Tamura, Yasuyuki Ishikawa, Sadao Shiosaka, Taro Mizuno, Takashi Tokuda, Masahiro Nunoshita, Jun OhtaAbstract:Abstract We present a technique for in vivo imaging and electrical interface deep inside the mouse brain using a single complementary metal–oxide semiconductor (CMOS) sensor. In this work, we have developed a device which incorporates an imaging array, electrodes, illumination light source and chemical delivery needle. The device encompasses the functionalities for fluorescence imaging and electrophysiological experiments simultaneously. Micro-electro-mechanical systems (MEMS) microfabrication technique is used to post-process the CMOS sensor chip. Integration of light emitting diodes (LEDs) for illumination and formation of on-chip platinum electrodes for electrical interface with neurons complete the packaged device. Using the device, we performed fluorescence imaging and electrophysiological experiments inside the mouse brain. We have successfully induced synaptic response when the Schaffer-Collateral Pathway of the mouse hippocampus was stimulated using the on-chip Pt electrodes with current intensities from 200 μA to 1 mA. Furthermore, we have verified empirically that this technique has minimal effect on the hippocampus.
Lisa M. Monteggia - One of the best experts on this subject based on the ideXlab platform.
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Genetic Dissection of Presynaptic and Postsynaptic BDNF-TrkB Signaling in Synaptic Efficacy of CA3-CA1 Synapses.
Cell reports, 2018Co-Authors: Pei Yi Lin, Ege T. Kavalali, Lisa M. MonteggiaAbstract:Summary Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), regulate long-term potentiation (LTP) in the hippocampus, although the sites of BDNF-TrkB receptors in this process are controversial. We used a viral-mediated approach to delete BDNF or TrkB specifically in CA1 and CA3 regions of the Schaffer Collateral Pathway. Deletion of BDNF in CA3 or CA1 revealed that presynaptic BDNF is involved in LTP induction, while postsynaptic BDNF contributes to LTP maintenance. Similarly, loss of presynaptic or postsynaptic TrkB receptors leads to distinct LTP deficits, with presynaptic TrkB required to maintain LTP, while postsynaptic TrkB is essential for LTP formation. In addition, loss of TrkB in CA3 significantly diminishes release probability, uncovering a role for presynaptic TrkB receptors in basal neurotransmission. Taken together, this direct comparison of presynaptic and postsynaptic BDNF-TrkB reveals insight into BDNF release and TrkB activation sites in hippocampal LTP.
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Genetic Dissection of Presynaptic and Postsynaptic BDNF-TrkB Signaling in Synaptic Efficacy of CA3-CA1 Synapses
Elsevier, 2018Co-Authors: Pei Yi Lin, Ege T. Kavalali, Lisa M. MonteggiaAbstract:Summary: Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB), regulate long-term potentiation (LTP) in the hippocampus, although the sites of BDNF-TrkB receptors in this process are controversial. We used a viral-mediated approach to delete BDNF or TrkB specifically in CA1 and CA3 regions of the Schaffer Collateral Pathway. Deletion of BDNF in CA3 or CA1 revealed that presynaptic BDNF is involved in LTP induction, while postsynaptic BDNF contributes to LTP maintenance. Similarly, loss of presynaptic or postsynaptic TrkB receptors leads to distinct LTP deficits, with presynaptic TrkB required to maintain LTP, while postsynaptic TrkB is essential for LTP formation. In addition, loss of TrkB in CA3 significantly diminishes release probability, uncovering a role for presynaptic TrkB receptors in basal neurotransmission. Taken together, this direct comparison of presynaptic and postsynaptic BDNF-TrkB reveals insight into BDNF release and TrkB activation sites in hippocampal LTP. : Lin et al. directly compare a role for presynaptic and postsynaptic BDNF and TrkB receptors in hippocampal LTP. They find that LTP induction is mediated by anterograde BDNF-TrkB signaling, while both anterograde and retrograde BDNF-TrkB signaling persists presynaptically and postsynaptically for LTP maintenance. Keywords: BDNF, TrkB, hippocampus, synaptic plasticity, LTP, presynaptic, postsynapti
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In Vivo Analysis of MEF2 Transcription Factors in Synapse Regulation and Neuronal Survival
2016Co-Authors: Waseem M. Akhtar, Ege T. Kavalali, Mi-sung Kim, Megumi Adachi, Michael J. Morris, James A. Richardson, Rhonda Bassel-duby, Eric N. Olson, Lisa M. MonteggiaAbstract:MEF2 (A–D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer Collateral Pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for MEF2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/ dTKO). Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the MEF2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that MEF2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of MEF2C isoform in the brain an
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In vivo analysis of MEF2 transcription factors in synapse regulation and neuronal survival.
PloS one, 2012Co-Authors: M. Waseem Akhtar, Ege T. Kavalali, Mi-sung Kim, Megumi Adachi, Michael J. Morris, James A. Richardson, Rhonda Bassel-duby, Eric N. Olson, Lisa M. MonteggiaAbstract:MEF2 (A–D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer Collateral Pathway long-term potentiation, or the number of dendritic spines. Since previous work has established a critical role for MEF2C in hippocampal plasticity, we generated a Mef2a, Mef2c and Mef2d brain-specific triple KO (Mef2a/c/dTKO). Mef2a/c/d TKO mice have early postnatal lethality with increased neuronal apoptosis, indicative of a redundant role for the MEF2 factors in neuronal survival. We examined synaptic plasticity in the intact neurons in the Mef2a/c/d TKO mice and found significant impairments in short-term synaptic plasticity suggesting that MEF2C is the major isoform involved in hippocampal synaptic function. Collectively, these data highlight the key in vivo role of MEF2C isoform in the brain and suggest that MEF2A and MEF2D have only subtle roles in regulating hippocampal synaptic function.
Yasuyuki Ishikawa - One of the best experts on this subject based on the ideXlab platform.
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Neuropsin--a possible modulator of synaptic plasticity.
Journal of chemical neuroanatomy, 2011Co-Authors: Sadao Shiosaka, Yasuyuki IshikawaAbstract:Accumulating evidence has suggested pivotal roles for neural proteases in development, maturation, aging, and cognitive functions. Among such proteases, neuropsin, a kallikrein gene-related (KLK) endoprotease, appears to have a significant plasticity function that has been analyzed primarily in the hippocampal Schaffer-Collateral Pathway. In this article, after reviewing the general features of neuropsin, its role in Schaffer-Collateral synaptic plasticity is discussed in some detail. Enzymatically active neuropsin is necessary to establish the early phase of long-term potentiation (LTP). This type of LTP, which can be elicited by rather weak tetanic stimulation, is significant in synaptic late association between two independent hippocampal synapses. Neuropsin deficiency completely impaired the early phase of LTP, leading to the absence of late associativity. Associations between early and persistent-LTP synapses may be related to mammalian working memory and consequently integration in learning and memory.
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Diversity of neuropsin (KLK8)-dependent synaptic associativity in the hippocampal pyramidal neuron.
The Journal of physiology, 2011Co-Authors: Yasuyuki Ishikawa, Hideki Tamura, Sadao ShiosakaAbstract:Hippocampal early (E-) long-term potentiation (LTP) and long-term depression (LTD) elicited by a weak stimulus normally fades within 90 min. Late (L-) LTP and LTD elicited by strong stimuli continue for >180 min and require new protein synthesis to persist. If a strong tetanus is applied once to synaptic inputs, even a weak tetanus applied to another synaptic input can evoke persistent LTP. A synaptic tag is hypothesized to enable the capture of newly synthesized synaptic molecules. This process, referred to as synaptic tagging, is found between not only the same processes (i.e. E- and L-LTP; E- and L-LTD) but also between different processes (i.e. E-LTP and L-LTD; E-LTD and L-LTP) induced at two independent synaptic inputs (cross-tagging). However, the mechanisms of synaptic tag setting remain unclear. In our previous study, we found that synaptic associativity in the hippocampal Schaffer Collateral Pathway depended on neuropsin (kallikrein-related peptidase 8 or KLK8), a plasticity-related extracellular protease. In the present study, we investigated how neuropsin participates in synaptic tagging and cross-tagging. We report that neuropsin is involved in synaptic tagging during LTP at basal and apical dendritic inputs. Moreover, neuropsin is involved in synaptic tagging and cross-tagging during LTP at apical dendritic inputs via integrin β1 and calcium/calmodulin-dependent protein kinase II signalling. Thus, neuropsin is a candidate molecule for the LTP-specific tag setting and regulates the transformation of E- to L-LTP during both synaptic tagging and cross-tagging.
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Neuropsin (KLK8)-Dependent and -Independent Synaptic Tagging in the Schaffer-Collateral Pathway of Mouse Hippocampus
Journal of Neuroscience, 2008Co-Authors: Yasuyuki Ishikawa, Yoichiro Horii, Hideki Tamura, Sadao ShiosakaAbstract:Hippocampal early long-term potentiation (LTP) elicited by a weak (one or two) tetanic stimulus normally fades away within 90 min. Late LTP elicited by strong (four) stimuli lasts >180 min and requires new protein synthesis to persist. If a strong tetanus is injected once into a synapse, even a weak tetanus injected into another synapse can evoke persistent LTP. It was hypothesized that a synaptic tag enables capture of newly synthesized synaptic molecules. Here, we found two synaptic capture mechanisms for a weakly stimulated synapse to acquire persistency (i.e., neuropsin dependent and independent). The single tetanus evokes a neuropsin-dependent form that follows downstream signaling into integrin/actin signal and L-type voltage-dependent Ca2+ channel (LVDCC) Pathway. Additionally, a neuropsin-independent form of synaptic capture is evoked by a stronger (two) tetanus than the former. Both forms converging on LVDCC might serve different associative memories depending on their input strength. Our study strongly supports the hypothesis of synaptic tagging and demonstrates that neuropsin-dependent late associativity is particularly important in nonstressful associative memory.
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An implantable and fully integrated complementary metal–oxide semiconductor device for in vivo neural imaging and electrical interfacing with the mouse hippocampus
Sensors and Actuators A-physical, 2007Co-Authors: Hideki Tamura, Yasuyuki Ishikawa, Sadao Shiosaka, Taro Mizuno, Takashi Tokuda, Masahiro Nunoshita, Jun OhtaAbstract:Abstract We present a technique for in vivo imaging and electrical interface deep inside the mouse brain using a single complementary metal–oxide semiconductor (CMOS) sensor. In this work, we have developed a device which incorporates an imaging array, electrodes, illumination light source and chemical delivery needle. The device encompasses the functionalities for fluorescence imaging and electrophysiological experiments simultaneously. Micro-electro-mechanical systems (MEMS) microfabrication technique is used to post-process the CMOS sensor chip. Integration of light emitting diodes (LEDs) for illumination and formation of on-chip platinum electrodes for electrical interface with neurons complete the packaged device. Using the device, we performed fluorescence imaging and electrophysiological experiments inside the mouse brain. We have successfully induced synaptic response when the Schaffer-Collateral Pathway of the mouse hippocampus was stimulated using the on-chip Pt electrodes with current intensities from 200 μA to 1 mA. Furthermore, we have verified empirically that this technique has minimal effect on the hippocampus.
Bartlett W. Mel - One of the best experts on this subject based on the ideXlab platform.
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Neuron Viewpoint Capacity-Enhancing Synaptic Learning Rules in a Medial Temporal Lobe Online Learning Model
2013Co-Authors: Bartlett W. MelAbstract:Medial temporal lobe structures are responsible for recording the continuous stream of autobiographical memories that define our unique personal history. Remarkably, these areas can construct durable memories from brief exposures to the constantly changing activity patterns arriving from antecedent cortical areas. Using a computer model of the hippocampal Schaffer Collateral Pathway that incorporates evidence for dendritic spikes in CA1 pyramidal neurons, we searched for biologically-plausible longterm potentiation (LTP) and homeostatic depression (HD) rules that maximize ‘‘online’ ’ learning capacity. We found memory utilization is most efficient when (1) very few synapses are modified to store each pattern, (2) LTP, the learning operation, is dendrite-specific and gated by distinct pre- and postsynaptic thresholds, (3) HD, the forgetting operation, co-occurs with LTP and targets least-recently potentiated synapses, and (4) both LTP and HD are all-or-none, leading de facto to binary-valued synaptic weights. In networks containing up to 40 million synapses, the learning scheme led to orderof-magnitude capacity increases compared to conventional plasticity rules
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Capacity-enhancing synaptic learning rules in a medial temporal lobe online learning model.
Neuron, 2009Co-Authors: Bartlett W. MelAbstract:Summary Medial temporal lobe structures are responsible for recording the continuous stream of autobiographical memories that define our unique personal history. Remarkably, these areas can construct durable memories from brief exposures to the constantly changing activity patterns arriving from antecedent cortical areas. Using a computer model of the hippocampal Schaffer Collateral Pathway that incorporates evidence for dendritic spikes in CA1 pyramidal neurons, we searched for biologically-plausible long-term potentiation (LTP) and homeostatic depression (HD) rules that maximize "online" learning capacity. We found memory utilization is most efficient when (1) very few synapses are modified to store each pattern, (2) LTP, the learning operation, is dendrite-specific and gated by distinct pre- and postsynaptic thresholds, (3) HD, the forgetting operation, co-occurs with LTP and targets least-recently potentiated synapses, and (4) both LTP and HD are all-or-none, leading de facto to binary-valued synaptic weights. In networks containing up to 40 million synapses, the learning scheme led to order-of-magnitude capacity increases compared to conventional plasticity rules.
