Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP

Hosokawa, Toshiyuki; Rusakov, Dmitri A.; Bliss, T. V. P.; Fine, Alan

doi:10.1523/jneurosci.15-08-05560.1995

Cited by 180 publications

(130 citation statements)

References 112 publications

(122 reference statements)

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…There has been debate regarding the magnitude and time course of structural changes during LTP (Desmond and Levy, 1983;Hosokawa et al, 1995;Sorra and Harris, 1998;Engert and Bonhoeffer, 1999;Maletic-Savatic et al, 1999;Toni et al, 1999;Ostroff et al, 2002;Lang et al, 2004;Matsuzaki et al, 2004;Okamoto et al, 2004). Here, we briefly drive bursting of endogenous synaptic activity in organotypic hippocampal slices to produce synaptic enhancement that mimics LTP (Otmakhov et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation

Kopec

Li²,

Wei³

et al. 2006

J. Neurosci.

444

407

View full text Add to dashboard Cite

The changes in synaptic morphology and receptor content that underlie neural plasticity are poorly understood. Here, we use a pHsensitive green fluorescent protein to tag recombinant glutamate receptors and monitor their dynamics onto dendritic spine surfaces. We show that chemically induced long-term potentiation (chemLTP) drives robust exocytosis of AMPA receptors. In contrast, the same stimulus produces a small reduction of NMDA receptors from the spine surface. chemLTP produces similar modification of small and large spines. Interestingly, during chemLTP induction, spines increase in volume before accumulation of AMPA receptors on their surface, indicating that distinct mechanisms underlie changes in morphology and receptor content.

show abstract

Section: Discussionmentioning

confidence: 99%

Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation

Kopec

Li²,

Wei³

et al. 2006

J. Neurosci.

444

407

View full text Add to dashboard Cite

show abstract

“…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.

View full text Add to dashboard Cite

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

“…We also tested whether reagents that stimulate activity would alter spine motility. Application of N-methyl-D-aspartate (1-50 M; n ϭ 1 hippocampus, n ϭ 1 cortex) or ''potentiation'' medium containing tetraethylammonium (19) did not affect spine motility ( Fig. 5f; n ϭ 3 hippocampus, n ϭ 2 cortex).…”

Section: Gfp-labeled Cells In Acute and Cultured Slices Have Normal Mmentioning

confidence: 92%

Developmental regulation of spine motility in the mammalian central nervous system

Dunaevsky

Tashiro

Majewska

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

397

336

View full text Add to dashboard Cite

The function of dendritic spines, postsynaptic sites of excitatory input in the mammalian central nervous system (CNS), is still not well understood. Although changes in spine morphology may mediate synaptic plasticity, the extent of basal spine motility and its regulation and function remains controversial. We investigated spine motility in three principal neurons of the mouse CNS: cerebellar Purkinje cells, and cortical and hippocampal pyramidal neurons. Motility was assayed with time-lapse imaging by using two-photon microscopy of green fluorescent protein-labeled neurons in acute and cultured slices. In all three cell types, dendritic protrusions (filopodia and spines) were highly dynamic, exhibiting a diversity of morphological rearrangements over short (<1-min) time courses. The incidence of spine motility declined during postnatal maturation, but dynamic changes were still apparent in many spines in late-postnatal neurons. Although blockade or induction of neuronal activity did not affect spine motility, disruption of actin polymerization did. We hypothesize that this basal motility of dendritic protrusions is intrinsic to the neuron and underlies the heightened plasticity found in developing CNS. D endritic spines are the major sites of excitatory input in mammalian central nervous system (CNS) neurons (1, 2), but their function is still not well understood. In recent years, dendritic spines have been shown to act as biochemical compartments (3-5) that could mediate synapse-specific plasticity (6, 7), perhaps through rapid changes in spine morphology (8).Indeed, recent studies have demonstrated that activity can elicit new spine-like protrusions (9, 10). Nevertheless, the question of whether spines are inherently motile remains controversial. In developing hippocampal neurons from both dissociated and slice cultures, dendritic filopodia, proposed to be precursors of mature spines, are highly dynamic (11,12). However, after synapse formation in culture and in acute slices of mature hippocampus, spines appear to be relatively immotile (12,13). In contrast, spines on hippocampal neurons in long-term cultures are extremely dynamic, even though these neurons bear synaptic contacts (14).To determine the extent of motility of dendritic spines, its developmental regulation and mechanisms, we imaged three major classes of spiny neurons of the CNS: cerebellar Purkinje neurons, and pyramidal neurons from cortex and hippocampus. Acute or cultured slices were transfected with enhanced green fluorescent protein DNA, expressed under a cytomegalovirus promoter (CMV-EGFP), by using biolistic gene transfer (15). Labeled cells were then imaged by using a custom-built twophoton microscope (16). We find that in the cells examined at mid-to late-postnatal stages, the majority of dendritic spines are motile structures over time scales as short as a minute, and that motility subsides, although does not disappear, with increasing age of the cell. Spines are motile in both cultured and acute cortical slices of the same chronologi...

show abstract

Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP

Cited by 180 publications

References 112 publications

Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation

Glutamate Receptor Exocytosis and Spine Enlargement during Chemically Induced Long-Term Potentiation

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

Developmental regulation of spine motility in the mammalian central nervous system

Contact Info

Product

Resources

About