The Cell Biology of Synaptic Plasticity

Ho, Victoria M.; Lee, Ji-Ann; Martin, Kelsey C.

doi:10.1126/science.1209236

Cited by 453 publications

(376 citation statements)

References 65 publications

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“…The ability to visualize newly synthesized proteomes in biological systems will greatly advance our understanding of complex cellular functions occurring in space and time (1)(2)(3)(4). Currently, this endeavor is mainly pursued by several distinct contrast mechanisms including fluorescence staining, autoradiography, and mass spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

“…Many intricate biological processes, such as cell growth, differentiation, diseases, and response to environmental stimuli, require protein synthesis and translational control (1). In particular, long-lasting forms of synaptic plasticity, such as those underlying long-term memory, require new protein synthesis in a space-and time-dependent manner (2)(3)(4). Therefore, direct visualization and quantification of newly synthesized proteins at a global level are indispensable to unraveling the spatial-temporal characteristics of the proteomes in live cells.…”

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confidence: 99%

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Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

Lu¹,

Shen³

et al. 2013

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

208

223

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Synthesis of new proteins, a key step in the central dogma of molecular biology, has been a major biological process by which cells respond rapidly to environmental cues in both physiological and pathological conditions. However, the selective visualization of a newly synthesized proteome in living systems with subcellular resolution has proven to be rather challenging, despite the extensive efforts along the lines of fluorescence staining, autoradiography, and mass spectrometry. Herein, we report an imaging technique to visualize nascent proteins by harnessing the emerging stimulated Raman scattering (SRS) microscopy coupled with metabolic incorporation of deuterium-labeled amino acids. As a first demonstration, we imaged newly synthesized proteins in live mammalian cells with high spatial-temporal resolution without fixation or staining. Subcellular compartments with fast protein turnover in HeLa and HEK293T cells, and newly grown neurites in differentiating neuron-like N2A cells, are clearly identified via this imaging technique. Technically, incorporation of deuterium-labeled amino acids is minimally perturbative to live cells, whereas SRS imaging of exogenous carbon-deuterium bonds (C-D) in the cell-silent Raman region is highly sensitive, specific, and compatible with living systems. Moreover, coupled with label-free SRS imaging of the total proteome, our method can readily generate spatial maps of the quantitative ratio between new and total proteomes. Thus, this technique of nonlinear vibrational imaging of stable isotope incorporation will be a valuable tool to advance our understanding of the complex spatial and temporal dynamics of newly synthesized proteome in vivo.stable isotope labeling | stimulated Raman microscopy | protein synthesis

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

Lu¹,

Shen³

et al. 2013

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

208

223

View full text Add to dashboard Cite

show abstract

“…At the cellular level, these modifications underpin synaptic plasticity (Citri and Malenka, 2008;Ho et al, 2011), and in the whole animal support learning and memory (Morris, 2006;Neves et al, 2008) and its response to the environment (Nithianantharajah and Hannan, 2006;Baroncelli et al, 2010). These changes involve both functional and structural adaptations in terms of intrinsic excitability (Davis, 2006), postsynaptic glutamate receptor complement (Kerchner and Nicoll, 2008;Kessels and Malinow, 2009), neurotransmitter release (Citri and Malenka, 2008), and in the shape and density of dendritic spines, axonal arbors, and synaptic boutons (Holtmaat and Svoboda, 2009;Hübener and Bonhoeffer, 2010).…”

Section: Introductionmentioning

confidence: 99%

MSK1 Regulates Homeostatic and Experience-Dependent Synaptic Plasticity

Corrêa¹,

Hunter

Palygin³

et al. 2012

J. Neurosci.

128

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The ability of neurons to modulate synaptic strength underpins synaptic plasticity, learning and memory, and adaptation to sensory experience. Despite the importance of synaptic adaptation in directing, reinforcing, and revising the behavioral response to environmental influences, the cellular and molecular mechanisms underlying synaptic adaptation are far from clear. Brain-derived neurotrophic factor (BDNF) is a prime initiator of structural and functional synaptic adaptation. However, the signaling cascade activated by BDNF to initiate these adaptive changes has not been elucidated. We have previously shown that BDNF activates mitogen-and stress-activated kinase 1 (MSK1), which regulates gene transcription via the phosphorylation of both CREB and histone H3. Using mice with a kinase-dead knock-in mutation of MSK1, we now show that MSK1 is necessary for the upregulation of synaptic strength in response to environmental enrichment in vivo. Furthermore, neurons from MSK1 kinase-dead mice failed to show scaling of synaptic transmission in response to activity deprivation in vitro, a deficit that could be rescued by reintroduction of wild-type MSK1. We also show that MSK1 forms part of a BDNF-and MAPK-dependent signaling cascade required for homeostatic synaptic scaling, which likely resides in the ability of MSK1 to regulate cell surface GluA1 expression via the induction of Arc/Arg3.1. These results demonstrate that MSK1 is an integral part of a signaling pathway that underlies the adaptive response to synaptic and environmental experience. MSK1 may thus act as a key homeostat in the activity-and experience-dependent regulation of synaptic strength.

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“…Modulation of synaptic plasticity is highly controlled by brain-derived neurotropic factor (BDNF) protein binding to specific tropomyosin receptor kinase B (TrkB) Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats receptors (11,12). BDNF is a member of the neurotrophin family (13,14), which is known to not only promote the activity of nerve growth, but also to modulate synaptic plasticity (15). For instance, numerous studies have indicated that BDNF enhances hippocampal synaptic plasticity by inducing local protein synthesis in the pre-synaptic terminal and post-synaptic dendrites of rats with cerebral ischemic injury (16,17).…”

Section: Introductionmentioning

confidence: 99%

Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats

Lin

et al. 2017

Experimental and Therapeutic Medicine

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Abstract.A previous study by our group found that electro-acupuncture (EA) at the Shenting (DU24) and Baihui (DU20) acupoints ameliorates cognitive impairment in rats with cerebral ischemia-reperfusion (I/R) injury. However, the precise mechanism of action has remained largely unknown. The present study investigated whether brain-derived neurotropic factor (BDNF) mediates hippocampal synaptic plasticity as the underlying mechanism. Rats were randomly divided into three groups: The sham operation control (Sham) group, the focal cerebral ischemia-reperfusion (I/R) group, and the I/R with EA treatment (I/R+EA) group. The I/R+EA group received EA treatment at the Shenting (DU24) and Baihui (DU20) acupoints after the operation. EA treatment was found to ameliorate neurological deficits (P<0.05) and reduce the cerebral infarct volume (P<0.01). In addition, EA improved cognitive function in cerebral I/R-injured rats (P<0.05). Furthermore, EA treatment promoted synaptic plasticity. Simultaneously, EA increased the hippocampal expression of BDNF, its high-affinity tropomyosin receptor kinase B (TrkB) and post-synaptic density protein-95 (PSD-95) in the rats with cerebral I/R injury. Collectively, the findings suggested that BDNF-mediated hippocampal synaptic plasticity may be one mechanism via which EA treatment at the Shenting (DU24) and Baihui (DU20) acupoints improves cognitive function in cerebral I/R injured rats. IntroductionIn 2011, an estimated 795,000 individuals experienced a stroke event in the United States of America (1). Stroke is one of the most common causes of cognitive impairment (2-4). According to different subtypes and diagnostic criteria of stroke, 17-92% of patients present with cognitive impairment 3 months after a stroke (5). Cognitive impairment can cause a variety of symptoms, such as a decline in attention, memory and problem-solving capability (6); therefore, prevention and treatment of stroke with cognitive impairment has become a priority in the global health sector.Acupuncture at the Shenting (DU24) and Baihui (DU20) acupoints has been used in China to treat cognitive impairment for thousands of years. They are located on a branch of the Du Meridian that runs over the head, which are associated with cognitive function in Traditional Chinese Medicine. Previous studies by our group have confirmed the efficacy of electro-acupuncture (EA) on the Shenting (DU24) and Baihui (DU20) acupoints in the rehabilitation of cognitive impairment in experimental settings (7,8).Although the pathogenic mechanisms of post-stoke cognitive impairment are complex, decreased hippocampal synaptic plasticity has been suggested to be one of the key elements (9,10). Modulation of synaptic plasticity is highly controlled by brain-derived neurotropic factor (BDNF) protein binding to specific tropomyosin receptor kinase B (TrkB) Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats

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The Cell Biology of Synaptic Plasticity

Cited by 453 publications

References 65 publications

Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy

MSK1 Regulates Homeostatic and Experience-Dependent Synaptic Plasticity

Electro-acupuncture ameliorates cognitive impairment via improvement of brain-derived neurotropic factor-mediated hippocampal synaptic plasticity in cerebral ischemia-reperfusion injured rats

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