Sequential changes in the synaptic structural profile following long-term potentiation in the rat dentate gyrus: III. Long-term maintenance phase

Weeks, Andrew C.W.; Ivanco, Tammy L.; LeBoutillier, Janelle C.; Racine, R.; Petit, Ted L.

doi:10.1002/1098-2396(200104)40:1<74::aid-syn1028>3.0.co;2-d

Cited by 48 publications

(27 citation statements)

References 29 publications

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“…Evidence indicates that persistent LTP occurs when small stubby dendritic spines are converted into large mushroom-shaped spines through a mechanism dependent on local actin polymerization (Weeks et al, 2001;Fukazawa et al, 2003;Harris et al, 2003;Matsuzaki et al, 2004). Expansion of the PSD and spine head may depend on a number of F-actin functions, including tethering of receptors and signaling complexes, trafficking of receptors, positioning of polyribosomes, and modulation of translation factor activity (Kim and Lisman, 1999;Halpain, 2000;Zhou et al, 2001;Matsuzaki et al, 2004;Zito et al, 2004;Carlisle and Kennedy, 2005;Bramham and Wells, 2007).…”

Section: Discussionmentioning

confidence: 99%

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Messaoudi¹,

Kanhema²,

Soulé³

et al. 2007

J. Neurosci.

418

463

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New gene expression is necessary for long-term potentiation (LTP) consolidation, yet roles for specific activity-induced mRNAs have not been defined. Here we probed the dynamic function of activity-induced Arc (activity-regulated cytoskeletal-associated protein)/Arg3.1 (activity-regulated gene 3.1 protein homolog) mRNA using brief, local infusions of antisense (AS) oligodeoxynucleotides at multiple time points during dentate gyrus LTP in vivo. Surprisingly, early Arc synthesis is necessary for early expression of LTP, whereas sustained synthesis is required to generate stably modified synapses. AS application 2 h after LTP induction results in a rapid and permanent reversal of LTP. This reversal is associated with rapid knockdown of upregulated Arc, dephosphorylation of actin depolymerization factor/cofilin, and loss of nascent filamentous actin (F-actin) at synaptic sites. Infusion of the F-actin stabilizing drug jasplakinolide during LTP maintenance blocks the ability of AS to reverse LTP. These results couple activity-induced expression of Arc to expansion of the actin cytoskeleton underlying enduring LTP. Furthermore, Arc synthesis is required for both the induction and consolidation of LTP elicited by local BDNF infusion, thus identifying Arc as a key molecular effector of BDNF in synaptic plasticity.

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Section: Discussionmentioning

confidence: 99%

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Messaoudi¹,

Kanhema²,

Soulé³

et al. 2007

J. Neurosci.

418

463

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“…For example, aged animals with impaired cognition have been reported to demonstrate reductions in the surface area of synapses (Nicholson et al, 2004), and the PSD area of specific types of synapses in young rats increased both as a function of learning (Geinisman et al, 2004) and with LTP induction in the hippocampus (Geinisman et al, 1991; Geinisman et al, 1993; Geinisman et al, 1996; Weeks et al, 1999; Weeks et al, 2001). Previous reports also have indicated that the abundance of AMPA-type glutamate receptors is related to the size and complexity of the PSD (Ganeshina et al, 2004a; Ganeshina et al, 2004b; Nicholson et al, 2006; Nicholson and Geinisman, 2009).…”

Section: Discussionmentioning

confidence: 99%

Age-related synapse loss in hippocampal CA3 is not reversed by caloric restriction

et al. 2010

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Caloric restriction (CR) is a reduction of total caloric intake without a decrease in micronutrients or a disproportionate reduction of any one dietary component. While CR attenuates age-related cognitive deficits in tasks of hippocampal-dependent memory, the cellular mechanisms by which CR improves this cognitive decline are poorly understood. Previously, we have reported agerelated decreases in key synaptic proteins in the CA3 region of the hippocampus that are stabilized by lifelong CR. In the present study, we examined possible age-related changes in the functional microcircuitry of the synapses in the stratum lacunosum-moleculare (SL-M) of the CA3 region of the hippocampus, and whether lifelong CR might prevent these age-related alterations. We used serial electron microscopy to reconstruct and classify SL-M synapses and their postsynaptic spines. We analyzed synapse number and size as well as spine surface area and volume in young (10 mos.) and old (29 mos) ad libitum fed rats and in old rats that were calorically restricted from 4 months of age. We limited our analysis to SL-M because previous work demonstrated agerelated decreases in synaptophysin confined to this specific layer and region of the hippocampus. The results revealed an age-related decrease in macular axo-spinous synapses that was not reversed by CR that occurred in the absence of changes in the size of synapses or spines. Thus, the benefits of CR for CA3 function and synaptic plasticity may involve other biological effects including the stabilization of synaptic proteins levels in the face of age-related synapse loss. KeywordsDietary Restriction; Electron Microscopy; Serial Reconstruction; Synapses; Hippocampus; Rat Progressive cognitive impairment is a hallmark of the aging process in rodents. In particular, cognitive functions mediated by the hippocampus decline across lifespan. Interesting, old © 2010 IBRO. Published by Elsevier Ltd. All rights reserved Corresponding Author: Dr. Michelle M. Adams Psychology Department Bilkent University 06800 Bilkent Ankara -Turkey Phone: 90-312-290-1090 Fax: 90-312-290-2561 michelle@bilkent.edu.tr. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2011 December 1. Markowska and Savonenko, 2002). Although a broad range of anatomical, physiological, and biochemical studies have evaluated the effects of caloric restriction (CR) on the brain, a complete understanding of the interaction between the aging-related and CR-mediated changes that underlie the attenuation of cognitive...

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“…Synaptic remodeling in hippocampus both accompanies long-lasting LTP (Hosokawa et al 1995;Engert and Bonhoeffer 1999;Toni et al 1999;Weeks et al 2001;Lang et al 2004;Matsuzaki et al 2004;Nägerl et al 2004) and occurs with several hippocampal-dependent associative learning and memory tasks (Geinisman et al 2001;Eyre et al 2003;Leuner et al 2003;Rekart et al 2007). Stereological analyses of synapse density in the dentate gyrus molecular layer have shown that spine number begins to increase ∼3 h post-IA training, peaks by 6 h, then returns to baseline values by 72 h (O'Malley et al 2000).…”

Section: Discussionmentioning

confidence: 99%

The extracellular protease matrix metalloproteinase-9 is activated by inhibitory avoidance learning and required for long-term memory

Nagy¹,

Bozdagi²,

Huntley³

2007

Learn. Mem.

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Matrix metalloproteinases (MMPs) are a family of extracellularly acting proteolytic enzymes with well-recognized roles in plasticity and remodeling of synaptic circuits during brain development and following brain injury. However, it is now becoming increasingly apparent that MMPs also function in normal, nonpathological synaptic plasticity of the kind that may underlie learning and memory. Here, we extend this idea by investigating the role and regulation of MMP-9 in an inhibitory avoidance (IA) learning and memory task. We demonstrate that following IA training, protein levels and proteolytic activity of MMP-9 become elevated in hippocampus by 6 h, peak at 12-24 h, then decline to baseline values by ∼72 h. When MMP function is abrogated by intrahippocampal infusion of a potent gelatinase (MMP-2 and MMP-9) inhibitor 3.5 h following IA training, a time prior to the onset of training-induced elevation in levels, IA memory retention is significantly diminished when tested 1-3 d later. Animals impaired at 3 d exhibit robust IA memory when retrained, suggesting that such impairment is not likely attributed to toxic or other deleterious effects that permanently disrupt hippocampal function. In anesthetized adult rats, the effective distance over which synaptic plasticity is impaired by a single intrahippocampal infusion of the MMP inhibitor of the kind that blocks IA memory is ∼1200 µm. Taken together, these data suggest that IA training induces a slowly emerging, but subsequently protracted period of MMP-mediated proteolysis critical for enabling long-lasting synaptic modification that underlies long-term memory consolidation.New information is learned and remembered through functional and structural modifications of synaptic connections (Bliss and Collingridge 1993;Rogan et al. 1997;Rioult-Pedotti et al. 1998Jorntell and Hansel 2006;Pastalkova et al. 2006;Whitlock et al. 2006). Several kinds of learning and memory tasks have been shown to drive changes in neurotransmitter receptor function and/or localization (Cammarota et al. 1995;Bevilaqua et al. 2005;Rumpel et al. 2005;Whitlock et al. 2006), as well as induce over time changes in synapse number or morphology (O'Malley et al. 2000;Geinisman et al. 2001;Eyre et al. 2003;Leuner et al. 2003;Maviel et al. 2004;Lamprecht et al. 2006;Rekart et al. 2007). These observations suggest that there must be learninginduced cellular mechanisms for coordinating functional and structural remodeling of synaptic connectivity to enable longterm memory, but there is little known about the molecules that could fulfill such a role.Learning-related, regulated extracellular proteolysis could be one mechanism for coordinating functional and structural synaptic plasticity, thereby enabling memory (Huang et al. 1996;Madani et al. 1999;Calabresi et al. 2000;Pawlak et al. 2002;Tamura et al. 2006). It is well-recognized that extracellular matrix (ECM) proteins as well synaptic cell adhesion molecules contribute to both functional and structural aspects of synaptic plasticity, are modified by l...

show abstract

Sequential changes in the synaptic structural profile following long-term potentiation in the rat dentate gyrus: III. Long-term maintenance phase

Cited by 48 publications

References 29 publications

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Sustained Arc/Arg3.1 Synthesis Controls Long-Term Potentiation Consolidation through Regulation of Local Actin Polymerization in the Dentate GyrusIn Vivo

Age-related synapse loss in hippocampal CA3 is not reversed by caloric restriction

The extracellular protease matrix metalloproteinase-9 is activated by inhibitory avoidance learning and required for long-term memory

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