The Dendritic Branch Is the Preferred Integrative Unit for Protein Synthesis-Dependent LTP

Govindarajan, Arvind; Israely, Inbal; Huang, Shuying; Tonegawa, Susumu

doi:10.1016/j.neuron.2010.12.008

Cited by 322 publications

(427 citation statements)

References 53 publications

Supporting

Mentioning

390

Contrasting

Unclassified

Order By: Relevance

“…Remarkably, a local protein synthesis is assumed to be necessary for establishing late phase synaptic plasticity (14 -18). Considering that most of the changes may occur in a very limited space, as claimed by the cluster plasticity hypothesis (16,112), no dramatic increase of total protein level changes could be expected.…”

Section: Discussionmentioning

confidence: 97%

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Borovok

Nesher

Levin

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phasecurbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) Long-term synaptic plasticity is considered a cellular correlate of long-term memory (LTM) 1 . Contemporary understanding of memory formation is based on the initiation and maintenance of long-term synaptic plasticity (1-4), for which de novo protein synthesis is a vital requirement. De novo protein synthesis itself is secondary to activity-dependent changes in synapses that occur during learning processes. These activity changes trigger post-translational modifications of proteins initiating and sustaining multiple signal transduction pathways. In turn, these signaling pathways regulate changes in synaptic strength and connectivity by governing gene expression and protein translation (5-13). Depending on time elapsed since triggering of long-term synaptic plasticity, protein synthesis may be limited to the dendrites directly involved in the plasticity processes (14 -18). Multiple synaptic From the ‡Department

show abstract

Section: Discussionmentioning

confidence: 97%

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Borovok

Nesher

Levin

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…LTP maintenance is achieved by an interaction between input-specific 'synaptic tags', set by LTP induction, and the capture of PRPs synthesized in the soma or local dendritic domains. These are independent processes and can occur separately in time (Fonseca et al, 2004;Govindarajan et al, 2011;Redondo et al, 2010). Thus, according to the synaptic tagging and capture hypothesis, the maintenance of synaptic plasticity is a function of neuronal network activity and not only of the input stimulated at a given time.…”

Section: Introductionmentioning

confidence: 99%

Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

Fonseca

2013

Neuropsychopharmacol

View full text Add to dashboard Cite

Fear conditioning, a form of associative learning is thought to involve the induction of an associative long-term potentiation of cortical and thalamic inputs to the lateral amygdala. Here, we show that stimulation of the thalamic input can reinforce a transient form of plasticity (E-LTP) induced by weak stimulation of the cortical inputs. This synaptic cooperation occurs within a time window of 30 min, suggesting that synaptic integration at amygdala synapses can occur within large time windows. Interestingly, we found that synaptic cooperation is not symmetrical. Reinforcement of a thalamic E-LTP by subsequent cortical stimulation is only observed within a shorter time window. We found that activation of endocannabinoid CB1 receptors is involved in the time restriction of thalamic and cortical synaptic cooperation in an activity-dependent manner. Our results support the hypothesis that synaptic cooperation can underlie associative learning and that synaptic tagging and capture is a general mechanism in synaptic plasticity.

show abstract

“…24,25 Changes in spine morphology after chemical LTP (Refs. 12 and 22) and glutamate uncaging 26 could be observed, and it could be shown that spine neck plasticity regulates compartmentalization of synapses.…”

Section: Introductionmentioning

confidence: 95%

Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation

et al. 2016

View full text Add to dashboard Cite

Abstract. Emerging all-optical methods provide unique possibilities for noninvasive studies of physiological processes at the cellular and subcellular scale. On the one hand, superresolution microscopy enables observation of living samples with nanometer resolution. On the other hand, light can be used to stimulate cells due to the advent of optogenetics and photolyzable neurotransmitters. To exploit the full potential of optical stimulation, light must be delivered to specific cells or even parts of cells such as dendritic spines. This can be achieved with computer generated holography (CGH), which shapes light to arbitrary patterns by phase-only modulation. We demonstrate here in detail how CGH can be incorporated into a stimulated emission depletion (STED) microscope for photostimulation of neurons and monitoring of nanoscale morphological changes. We implement an original optical system to allow simultaneous holographic photostimulation and superresolution STED imaging. We present how synapses can be clearly visualized in live cells using membrane stains either with lipophilic organic dyes or with fluorescent proteins. We demonstrate the capabilities of this microscope to precisely monitor morphological changes of dendritic spines after stimulation. These all-optical methods for cell stimulation and monitoring are expected to spread to various fields of biological research in neuroscience and beyond. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

show abstract

The Dendritic Branch Is the Preferred Integrative Unit for Protein Synthesis-Dependent LTP

Cited by 322 publications

References 53 publications

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

Superresolving dendritic spine morphology with STED microscopy under holographic photostimulation

Contact Info

Product

Resources

About