The anticoagulant activated protein C (aPC) promotes metaplasticity in the hippocampus through an EPCR-PAR1-S1P1 receptors dependent mechanism.

Abstract:

:Thrombin and other clotting factors regulate long-term potentiation (LTP) in the hippocampus through the activation of the protease activated receptor 1 (PAR1) and consequent potentiation of N-methyl-d-aspartate receptor (NMDAR) functions. We have recently shown that the activation of PAR1 either by thrombin or the anticoagulant factor activated protein C (aPC) has differential effects on LTP. While thrombin activation of PAR1 induces an NMDAR-mediated slow onset LTP, which saturates the ability to induce further LTP in the exposed network, aPC stimulation of PAR1 enhances tetanus induced LTP through a voltage-gated calcium channels mediated mechanism. In this study, we addressed the mechanisms by which aPC enhances LTP in hippocampal slices. Using extracellular recordings, we show that a short tetanic stimulation, which does not induce LTP, is able to enhance plasticity in the presence of aPC through a mechanism that requires the activation of sphingosine-1 phosphate receptor 1 and intracellular Ca(2+) stores. These data identify aPC as a "metaplastic molecule", capable of shifting the threshold of LTP towards further potentiation. Our findings propose novel strategies to enhance plasticity in neurological diseases associated with the breakdown of the blood brain barrier and alterations in synaptic plasticity.

journal_name

Hippocampus

journal_title

Hippocampus

authors

Maggio N,Itsekson Z,Ikenberg B,Strehl A,Vlachos A,Blatt I,Tanne D,Chapman J

doi

10.1002/hipo.22288

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

1030-8

issue

8

eissn

1050-9631

issn

1098-1063

journal_volume

24

pub_type

杂志文章
  • Long-term potentiation and long-term depression induced by local application of ATP to hippocampal CA1 neurons of the guinea pig.

    abstract::The present study has investigated the role of ATP in the induction of synaptic plasticity, using local application of ATP by picopump administration into the stratum radiatum of guinea pig hippocampal region CA1. Excitatory postsynaptic currents (EPSCs) evoked by stimulation of Schaffer collateral/commissural afferen...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.7999

    authors: Yamazaki Y,Kaneko K,Fujii S,Kato H,Ito K

    更新日期:2003-01-01 00:00:00

  • Early life stress stimulates hippocampal reelin gene expression in a sex-specific manner: evidence for corticosterone-mediated action.

    abstract::Early life stress predisposes to the development of psychiatric disorders. In this context the hippocampal formation is of particular interest, because it is affected by stress on the structural and cognitive level. Since little is known how early life stress is translated on the molecular level, we mimicked early lif...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20907

    authors: Gross CM,Flubacher A,Tinnes S,Heyer A,Scheller M,Herpfer I,Berger M,Frotscher M,Lieb K,Haas CA

    更新日期:2012-03-01 00:00:00

  • Excitability changes within transverse lamellae of dentate granule cells and their longitudinal spread following orthodromic or antidromic activation.

    abstract::The functional organization of the perforant path input to the dentate gyrus of the exposed hippocampus was studied in adult rabbits anesthetized with urethane and chloralose. Electrical stimulation of perforant path fibers caused excitation of granule cells along narrow, nearly transverse strips (lamellae) of tissue....

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20538

    authors: Lømo T

    更新日期:2009-07-01 00:00:00

  • Serotonin neuronal release from dorsal hippocampus following electrical stimulation of the dorsal and median raphé nuclei in conscious rats.

    abstract::We have studied 5-hydroxytryptamine (5-HT) release in the hippocampal formation following electrical stimulation of the dorsal and median raphé nuclei in the behaving rat. The primary finding in this study is a decrease in neuronal release of serotonin in the dorsal hippocampal formation following electrical stimulati...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-1063(1998)8:3<262::AID-HIPO8>3.

    authors: Mokler DJ,Lariviere D,Johnson DW,Theriault NL,Bronzino JD,Dixon M,Morgane PJ

    更新日期:1998-01-01 00:00:00

  • Enhanced hippocampal neuronal excitability and LTP persistence associated with reduced behavioral flexibility in the maternal immune activation model of schizophrenia.

    abstract::Individuals with schizophrenia display a number of structural and cytoarchitectural alterations in the hippocampus, suggesting that other functions such as synaptic plasticity may also be modified. Altered hippocampal plasticity is likely to affect memory processing, and therefore any such pathology may contribute to ...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22193

    authors: Savanthrapadian S,Wolff AR,Logan BJ,Eckert MJ,Bilkey DK,Abraham WC

    更新日期:2013-12-01 00:00:00

  • Relational learning and transitive expression in aging and amnesia.

    abstract::Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255-257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accomp...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22501

    authors: Ryan JD,D'Angelo MC,Kamino D,Ostreicher M,Moses SN,Rosenbaum RS

    更新日期:2016-02-01 00:00:00

  • Cumulative long-term potentiation in the rat dentate gyrus correlates with, but does not modify, performance in the water maze.

    abstract::The electrically induced increase in hippocampal synaptic strength known as long-term potentiation (LTP) is thought to involve some of the same mechanisms as those mediating information storage during spatial learning. Physiological saturation of synaptic weights might therefore be expected to occlude spatial learning...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.450030205

    authors: Jeffery KJ,Morris RG

    更新日期:1993-04-01 00:00:00

  • Electrophysiology of regular firing cells in the rat perirhinal cortex.

    abstract::The electrophysiological properties of neurons in the rat perirhinal cortex were analyzed with intracellular recordings in an in vitro slice preparation. Cells included in this study (n = 59) had resting membrane potential (RMP) = -73.9 +/- 8.5 mV (mean +/- SD), action potential amplitude = 95.5 +/- 10.4 mV, input res...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.1081

    authors: D'Antuono M,Biagini G,Tancredi V,Avoli M

    更新日期:2001-01-01 00:00:00

  • Medial temporal lobe activation during encoding and retrieval of novel face-name pairs.

    abstract::The human medial temporal lobe (MTL) is known to be involved in declarative memory, yet the exact contributions of the various MTL structures are not well understood. In particular, the data as to whether the hippocampal region is preferentially involved in the encoding and/or retrieval of associative memory have not ...

    journal_title:Hippocampus

    pub_type: 临床试验,杂志文章

    doi:10.1002/hipo.20014

    authors: Kirwan CB,Stark CE

    更新日期:2004-01-01 00:00:00

  • A new human delayed-matching-to-place test in a virtual environment reverse-translated from the rodent watermaze paradigm: Characterization of performance measures and sex differences.

    abstract::Watermaze tests of place learning and memory in rodents and corresponding reverse-translated human paradigms in real or virtual environments are key tools to study hippocampal function. In common variants, the animal or human participant has to find a hidden goal that remains in the same place over many trials, allowi...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22992

    authors: Buckley MG,Bast T

    更新日期:2018-11-01 00:00:00

  • Disparate effects of long-term potentiation on evoked potentials and single CA1 neurons in the hippocampus of anesthetized rats.

    abstract::To examine the effects of long-term potentiation (LTP) on individual neurons in the intact brain, anesthetized rats were implanted with a recording stereotrode in the right CA1 layer of the hippocampus and a stimulating electrode in the right and left CA3 layers. The evoked and spontaneous firing of single CA1 neurons...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/1098-1063(2000)10:3<207::AID-HIPO1>3.0.CO;

    authors: Martin PD,Shapiro ML

    更新日期:2000-01-01 00:00:00

  • Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats.

    abstract::Animal studies on the effects of chronic variable stress during the peripubertal-juvenile period on hippocampal structure and function are lacking. Twenty-eight-day-old Sprague-Dawley rats were subjected to random, variable physical or social stress regimens for 4 weeks. Hippocampal volume was found to continue to gro...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.10207

    authors: Isgor C,Kabbaj M,Akil H,Watson SJ

    更新日期:2004-01-01 00:00:00

  • Ras-GRF2 mediates long-term potentiation, survival, and response to an enriched environment of newborn neurons in the hippocampus.

    abstract::Hippocampal adult neurogenesis contributes to key functions of the dentate gyrus (DG), including contextual discrimination. This is due, at least in part, to the unique form of plasticity that new neurons display at a specific stage of their development when compared with the surrounding principal neurons. In addition...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22313

    authors: Darcy MJ,Trouche S,Jin SX,Feig LA

    更新日期:2014-11-01 00:00:00

  • Partial coherence and frustration in self-organizing spherical grids.

    abstract::Nearby grid cells have been observed to express a remarkable degree of long-range order, which is often idealized as extending potentially to infinity. Yet their strict periodic firing and ensemble coherence are theoretically possible only in flat environments, much unlike the burrows which rodents usually live in. Ar...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.23144

    authors: Stella F,Urdapilleta E,Luo Y,Treves A

    更新日期:2020-04-01 00:00:00

  • A model of topological mapping of space in bat hippocampus.

    abstract::The mammalian hippocampus plays a key role in spatial learning and memory, but the exact nature of the hippocampal representation of space is still being explored. Recently, there has been a fair amount of success in modeling hippocampal spatial maps in rats, assuming a topological perspective on spatial information p...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22610

    authors: Hoffman K,Babichev A,Dabaghian Y

    更新日期:2016-10-01 00:00:00

  • Increased hippocampus to ventromedial prefrontal connectivity during the construction of episodic future events.

    abstract::Both the hippocampus and ventromedial prefrontal cortex (vmPFC) appear to be critical for episodic future simulation. Damage to either structure affects one's ability to remember the past and imagine the future, and both structures are commonly activated as part of a wider core network during future simulation. Howeve...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22812

    authors: Campbell KL,Madore KP,Benoit RG,Thakral PP,Schacter DL

    更新日期:2018-02-01 00:00:00

  • Lateralized functional components of spatial cognition in the avian hippocampal formation: evidence from single-unit recordings in freely moving homing pigeons.

    abstract::Previous research has revealed that the functional components of spatial cognition are lateralized in the forebrain of birds, including the hippocampal formation (HF). To investigate how HF cells in the left and right avian brain may differentially participate in representations of space, we recorded single-units from...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20139

    authors: Siegel JJ,Nitz D,Bingman VP

    更新日期:2006-01-01 00:00:00

  • Attention, configuration, and hippocampal function.

    abstract::We present a neural network that characterizes a remarkably large number of classical conditioning paradigms and describes the effects of many neurophysiological manipulations. First, the network 1) describes behavior in real time 2) comprises simple and configural stimulus representations, and 3) includes attentional...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-1063(1996)6:6<621::AID-HIPO6>3.

    authors: Buhusi CV,Schmajuk NA

    更新日期:1996-01-01 00:00:00

  • A natural form of learning can increase and decrease the survival of new neurons in the dentate gyrus.

    abstract::Granule cells born in the adult dentate gyrus undergo a 4-week developmental period characterized by high susceptibility to cell death. Two forms of hippocampus-dependent learning have been shown to rescue many of the new neurons during this critical period. Here, we show that a natural form of associative learning, s...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20097

    authors: Olariu A,Cleaver KM,Shore LE,Brewer MD,Cameron HA

    更新日期:2005-01-01 00:00:00

  • Effects of age and alcohol exposure during early life on pyramidal cell numbers in the CA1-CA3 region of the rat hippocampus.

    abstract::We have previously shown that exposing rats to a relatively high dose of ethanol during early postnatal life can result in an alteration in spatial learning ability. The hippocampal formation is known to be involved in the control of this ability. The purpose of the present study was to determine whether exposure of r...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.10155

    authors: Miki T,Harris SJ,Wilce PA,Takeuchi Y,Bedi KS

    更新日期:2004-01-01 00:00:00

  • Expression of the snoRNA host gene gas5 in the hippocampus is upregulated by age and psychogenic stress and correlates with reduced novelty-induced behavior in C57BL/6 mice.

    abstract::The growth arrest specific 5 (gas5) is a noncoding protein gene that hosts small nucleolar RNAs. Based on the observation that gas5 RNA level in the brain is highest in the hippocampus and remarkably enhanced in aged mice, we tested the hypothesis that gas5 is involved in functions controlled by the hippocampus and kn...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20701

    authors: Meier I,Fellini L,Jakovcevski M,Schachner M,Morellini F

    更新日期:2010-09-01 00:00:00

  • Changes in protein kinase C (PKC) activity, isozyme translocation, and GAP-43 phosphorylation in the rat hippocampal formation after a single-trial contextual fear conditioning paradigm.

    abstract::The hippocampus plays an important role in spatial learning and memory. However, the biochemical alterations that subserve this function remain to be fully elucidated. In this study, rats were subjected to a single-trial contextual fear conditioning (CFC) paradigm; the activation of different protein kinase C (PKC) su...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.10015

    authors: Young E,Cesena T,Meiri KF,Perrone-Bizzozero NI

    更新日期:2002-01-01 00:00:00

  • The role of the ventral dentate gyrus in olfactory pattern separation.

    abstract::Dorsoventral lesion studies of the hippocampus have indicated that the dorsal axis of the hippocampus is important for spatial processing and the ventral axis of the hippocampus is important for olfactory learning and memory and anxiety. There is some evidence to suggest that the ventral CA3 and ventral CA1 conduct pa...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22248

    authors: Weeden CS,Hu NJ,Ho LU,Kesner RP

    更新日期:2014-05-01 00:00:00

  • Postnatal neurogenesis in the dentate gyrus of the guinea pig.

    abstract::In all species examined, the dentate gyrus develops over an extended period that begins during gestation and continues up to adulthood. The aim of this study was to investigate the pattern of postnatal cell production in the dentate gyrus of the guinea pig, a rodent whose brain development has features more closely re...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20050

    authors: Guidi S,Ciani E,Severi S,Contestabile A,Bartesaghi R

    更新日期:2005-01-01 00:00:00

  • A single-trace dual-process model of episodic memory: a novel computational account of familiarity and recollection.

    abstract::Dual-process theories of episodic memory state that retrieval is contingent on two independent processes: familiarity (providing a sense of oldness) and recollection (recovering events and their context). A variety of studies have reported distinct neural signatures for familiarity and recollection, supporting dual-pr...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20606

    authors: Greve A,Donaldson DI,van Rossum MC

    更新日期:2010-02-01 00:00:00

  • Objects and landmarks: hippocampal place cells respond differently to manipulations of visual cues depending on size, perspective, and experience.

    abstract::Human navigation studies show that landmarks are used for orientation, whereas objects contribute to the contextual representation of an environment. What constitutes a landmark? Classic rodent studies show that hippocampal place fields are controlled by distal, polarizing cues. Place fields, however, are also influen...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22331

    authors: Scaplen KM,Gulati AA,Heimer-McGinn VL,Burwell RD

    更新日期:2014-11-01 00:00:00

  • Connections between the retrosplenial cortex and the hippocampal formation in the rat: a review.

    abstract::The retrosplenial cortex is situated at the crossroads between the hippocampal formation and many areas of the neocortex, but few studies have examined the connections between the hippocampal formation and the retrosplenial cortex in detail. Each subdivision of the retrosplenial cortex projects to a discrete terminal ...

    journal_title:Hippocampus

    pub_type: 杂志文章,评审

    doi:10.1002/hipo.450020102

    authors: Wyss JM,Van Groen T

    更新日期:1992-01-01 00:00:00

  • On the hippocampus and learned conditional responding: effects of aspiration versus ibotenate lesions.

    abstract::To study the possible involvement of the hippocampus in learned conditional responding, rats with aspiration lesions of the hippocampus and others that had the hippocampus removed with ibotenic acid were trained on concurrent Pavlovian conditional and nonconditional discriminations. In agreement with the results repor...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.450010110

    authors: Jarrard LE,Davidson TL

    更新日期:1991-01-01 00:00:00

  • Subcortical connections of the perirhinal, postrhinal, and entorhinal cortices of the rat. I. afferents.

    abstract::In this study the subcortical afferents for the rat PER areas 35 and 36, POR, and the lateral and medial entorhinal areas (LEA and MEA) were characterized. We analyzed 33 retrograde tract-tracing experiments distributed across the five regions. For each experiment, we estimated the total numbers, percentages, and dens...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.22603

    authors: Tomás Pereira I,Agster KL,Burwell RD

    更新日期:2016-09-01 00:00:00

  • Synaptophysin protein and mRNA expression in the human hippocampal formation from birth to old age.

    abstract::In the human neocortex, progressive synaptogenesis in early postnatal life is followed by a decline in synaptic density, then stability from adolescence until middle age. No comparable data are available in the hippocampus. In this study, the integral synaptic vesicle protein synaptophysin, measured immunoautoradiogra...

    journal_title:Hippocampus

    pub_type: 杂志文章

    doi:10.1002/hipo.20194

    authors: Eastwood SL,Weickert CS,Webster MJ,Herman MM,Kleinman JE,Harrison PJ

    更新日期:2006-01-01 00:00:00