The Spread of Ras Activity Triggered by Activation of a Single Dendritic Spine

Harvey, Christopher D.; Yasuda, Ryohei; Zhong, Haining; Svoboda, Karel

doi:10.1126/science.1159675

Cited by 391 publications

(574 citation statements)

References 29 publications

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“…Recent studies have shown that induction of plasticity at a single spine transiently lowers the plasticity threshold at adjacent spines (20). The mechanism underlying this phenomenon involves local spreading of signaling cascades from the activated spine to its neighbors, and some of these spreading signals are potent drivers of F-actin dynamics (24)(25)(26). Therefore, we asked if TBS2 induces F-actin polymerization in spines neighboring the synapses potentiated by TBS1.…”

Section: Resultsmentioning

confidence: 99%

“…We, therefore, assume that the priming effect of TBS1 on nonresponsive spines occurs at a stage located between the transmitter receptors and the multiple steps leading to the assembly and stabilization of actin filaments. Prior work suggesting that strong stimulation of single synapses causes the spread of active GTPases to neighboring spines (24,25) is of interest in this regard because these enzymes play critical roles in the production of stable LTP. It is also possible that TBS1 initiates a persistent change in nonresponsive spines that prepares them for the delayed arrival of TBS2.…”

Section: Discussionmentioning

confidence: 99%

“…Acute hippocampal brain slices (350-μm thick) from eGFP mice (30) (line M; 2-3 or 8-10 wk of age). Mice were killed by cervical dislocation, and following decapitation, the brain was rapidly removed and placed in choline chloride-based ice-cold cutting solution composed of the following (in mM): 110 choline-chloride, 25 Imaging and Glutamate Uncaging. Two-photon imaging and glutamate uncaging were performed using an Olympus FV1000MPE-TWIN multiphoton microscope with two Ti:sapphire lasers [895 nm for imaging eGFP using a MaiTai DeepSee laser (Spectraphysics); 720 nm for uncaging MNI-Glutamate using a Chameleon Vision II laser (Coherent)].…”

Section: Methodsmentioning

confidence: 99%

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Synaptic evidence for the efficacy of spaced learning

Kramár¹,

Babayan²,

Gavin

et al. 2012

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

142

189

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The superiority of spaced vs. massed training is a fundamental feature of learning. Here, we describe unanticipated timing rules for the production of long-term potentiation (LTP) in adult rat hippocampal slices that can account for one temporal segment of the spaced trials phenomenon. Successive bouts of naturalistic theta burst stimulation of field CA1 afferents markedly enhanced previously saturated LTP if spaced apart by 1 h or longer, but were without effect when shorter intervals were used. Analyses of Factin-enriched spines to identify potentiated synapses indicated that the added LTP obtained with delayed theta trains involved recruitment of synapses that were "missed" by the first stimulation bout. Single spine glutamate-uncaging experiments confirmed that less than half of the spines in adult hippocampus are primed to undergo plasticity under baseline conditions, suggesting that intrinsic variability among individual synapses imposes a repetitive presentation requirement for maximizing the percentage of potentiated connections. We propose that a combination of local diffusion from initially modified spines coupled with much later membrane insertion events dictate that the repetitions be widely spaced. Thus, the synaptic mechanisms described here provide a neurobiological explanation for one component of a poorly understood, ubiquitous aspect of learning.A n extensive body of experimental work indicates that periodic exposure to the same material results in better retention than a single "cramming" session. Although this distributed practice effect was first recognized in late 19th century (1-3), and has since been the subject of a very large psychological literature (4), the neurobiological processes that give rise to the phenomenon are poorly understood. Activity-dependent synaptic plasticity, and, in particular, long-term potentiation (LTP) of glutamatergic transmission, is thought to underlie rapid storage of new information (5, 6). Therefore, it is surprising that little experimental attention has been given to the possibility that specialized features of LTP may contribute to the spaced trials (distributed practice) effect. This likely reflects the lack of data indicating that the substrates of the potentiation effect include properties that are engaged, or enhanced, only by widely spaced stimulation episodes. Specifically, several types of studies point to the conclusion that the elaborate processes yielding fully developed LTP reach completion within 10-15 min (5, 7, 8); these findings do not include results suggestive of a delayed capacity for triggering additional changes to already potentiated synapses. There is considerable evidence for a later LTP stabilization step involving protein synthesis (9), but the effects of this on subsequent plasticity involve inputs other than those already expressing potentiation (10).Here, we describe a set of mechanisms and timing rules in hippocampus that result in widely spaced episodes of theta burst stimulation (TBS) generating a much greater degree of LT...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Synaptic evidence for the efficacy of spaced learning

Kramár¹,

Babayan²,

Gavin

et al. 2012

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

142

189

View full text Add to dashboard Cite

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“…Exactly how changes in H-Ras localization contribute to interneuron function is unknown. In pyramidal neurons, H-Ras activity is increased in glutamatestimulated dendritic spines and axonal growth cones (20,33). Additionally, H-Ras contributes to presynaptic neurotransmitter release via the ERK/Synapsin I pathway (34).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9

Chai

Cambronne

Eichhorn

et al. 2013

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

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Significance Most brain regions comprise numerous neural cell types that are distinct in function and molecular characteristics. We examined microRNA-134 (miR-134) activity in cortical cultures using a microRNA sensor and discovered that miR-134 was induced in response to neuronal activity in somatostatin- and calretinin-expressing interneurons but not in pyramidal neurons. We identified the palmitoylation enzyme DHHC9 as a direct target of miR-134 and showed that it contributed to the regulation of H-Ras in somatostatin interneurons. H-Ras is a signaling molecule crucial for neuronal development and function. This study uncovered an activity-dependent miR-134 regulatory pathway in cortical interneurons that can potentially affect membrane localization of multiple signaling molecules.

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“…Experiments using this approach to induce NMDAR-dependent LTP have shown that LTP can be induced at a single synapse without causing postsynaptic potentiation or depression of neighboring synapses (Matsuzaki et al 2004;Harvey and Svoboda 2007; but see Engert and Bonhoeffer 1997). However, interactions between neighboring synapses do occur, such that the intradendritic spread of the activated Ras from an active synapse briefly lowers the threshold for subsequent LTP induction at neighboring synapses (Harvey et al 2008).…”

Section: Induction Of Ltp and Ltdmentioning

confidence: 99%

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

Lüscher¹,

Malenka²

2012

Cold Spring Harbor Perspectives in Biology

774

647

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Long-term potentiation and long-term depression (LTP/LTD) can be elicited by activating N-methyl-D-aspartate (NMDA)-type glutamate receptors, typically by the coincident activity of pre-and postsynaptic neurons. The early phases of expression are mediated by a redistribution of AMPA-type glutamate receptors: More receptors are added to potentiate the synapse or receptors are removed to weaken synapses. With time, structural changes become apparent, which in general require the synthesis of new proteins. The investigation of the molecular and cellular mechanisms underlying these forms of synaptic plasticity has received much attention, because NMDA receptor-dependent LTP and LTD may constitute cellular substrates of learning and memory.L ong-term synaptic plasticity is a generic term that applies to a long-lasting experience-dependent change in the efficacy of synaptic transmission. Here we will focus on N-methyl-D-aspartate (NMDA) receptor-dependent synaptic potentiation (LTP) and depression (LTD), two forms of activity-dependent long-term changes in synaptic efficacy that have been extensively studied. Because both LTP and LTD are believed to represent cellular correlates of learning and memory, they have attracted considerable interest. In this article we will focus on the molecular and cellular mechanisms associated with LTP and LTD. As for other forms of long-term synaptic plasticity, a characterization of LTP and LTD involves describing the molecular mechanisms that are required to elicit the change (induction), followed by an investigation of the mechanism of expression (hours) and maintenance (days). The best-characterized form of NMDA receptor (NMDAR)-dependent LTP occurs between CA3 and CA1 pyramidal neurons of the hippocampus (Fig. 1). Throughout the chapter we will mostly refer to this specific form of LTP. At these CA3-CA1 Schaffer collateral synapses, the loci of both induction and expression are situated in the postsynaptic neuron. AMPA-TYPE AND NMDA-TYPE GLUTAMATE RECEPTORSAfter exocytotic release of the content of the synaptic vesicle from the presynaptic specialization (see Castillo 2012), the neurotransmitter

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The Spread of Ras Activity Triggered by Activation of a Single Dendritic Spine

Cited by 391 publications

References 29 publications

Synaptic evidence for the efficacy of spaced learning

Synaptic evidence for the efficacy of spaced learning

MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9

NMDA Receptor-Dependent Long-Term Potentiation and Long-Term Depression (LTP/LTD)

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