Spatial regulation of coordinated excitatory and inhibitory synaptic plasticity at dendritic synapses

The induction of synaptic plasticity at an individual dendritic glutamatergic spine can affect neighboring spines. This local modulation generates dendritic plasticity microdomains believed to expand the neuronal computational capacity. Here, we investigate whether local modulation of plasticity can also occur between glutamatergic synapses and adjacent GABAergic synapses. Using MNI-glutamate and DPNI-GABA double uncaging combined with electrophysiology, live-cell imaging and single-particle tracking, we find that the induction of LTP at an individual glutamatergic spine causes the depression of nearby GABAergic inhibitory synapses (within 3 microns), whereas more distant ones are potentiated. Notably, L-type calcium channels and calpain are required for this plasticity spreading. Overall, our data support a model whereby input-specific glutamatergic postsynaptic potentiation induces a spatially-regulated rearrangement of inhibitory synaptic strength in the surrounding area through short-range heterosynaptic interactions. Such local coordination of excitatory and inhibitory synaptic plasticity is expected to profoundly influence dendritic information processing and integration.

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Faculty Opinions recommendation of Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of PTP1B.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1060705.537867 ◽

2007 ◽

Author(s):

Karen Allen

Keyword(s):

Live Cell Imaging ◽

Cell Imaging ◽

Live Cell ◽

Spatial Regulation ◽

Substrate Interaction ◽

Enzyme Substrate

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Lysosome Mobility Probed with Live Cell Imaging and Single Particle Tracking

Biophysical Journal ◽

10.1016/j.bpj.2012.11.3597 ◽

2013 ◽

Vol 104 (2) ◽

pp. 651a

Author(s):

Debjyoti Bandyopadhyay ◽

Youngeun J. Kim ◽

Jairo Zapata ◽

Christine K. Payne

Keyword(s):

Particle Tracking ◽

Single Particle ◽

Live Cell Imaging ◽

Cell Imaging ◽

Single Particle Tracking ◽

Live Cell

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Live‐cell imaging of octaarginine‐modified polymer dots via single particle tracking

Cell Proliferation ◽

10.1111/cpr.12556 ◽

2019 ◽

Vol 52 (2) ◽

pp. e12556 ◽

Cited By ~ 2

Author(s):

Yao Luo ◽

Yuping Han ◽

Xingjie Hu ◽

Min Yin ◽

Changfeng Wu ◽

...

Keyword(s):

Particle Tracking ◽

Single Particle ◽

Live Cell Imaging ◽

Cell Imaging ◽

Single Particle Tracking ◽

Live Cell ◽

Modified Polymer ◽

Polymer Dots

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Faculty Opinions recommendation of Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of PTP1B.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1060705.523620 ◽

2007 ◽

Author(s):

Amy Barrios

Keyword(s):

Live Cell Imaging ◽

Cell Imaging ◽

Live Cell ◽

Spatial Regulation ◽

Substrate Interaction ◽

Enzyme Substrate

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Activity- and BDNF-Induced Plasticity of Miniature Synaptic Currents in ES Cell-Derived Neurons Integrated in a Neocortical Network

Journal of Neurophysiology ◽

10.1152/jn.00155.2005 ◽

2005 ◽

Vol 94 (6) ◽

pp. 4538-4543 ◽

Cited By ~ 17

Author(s):

Andrea Copi ◽

Kay Jüngling ◽

Kurt Gottmann

Keyword(s):

Synaptic Plasticity ◽

Action Potential ◽

Ampa Receptors ◽

Es Cells ◽

Embryonic Stem ◽

Synaptic Integration ◽

Inhibitory Synapses ◽

Es Cell ◽

Glutamatergic Synapses

In vitro differentiated embryonic stem (ES) cells have been proposed as potential donor cells for cell replacement therapies of neurodegenerative diseases. The functional synaptic integration of such cells appears conceivable because ES cell-derived neurons are well known to establish excitatory and inhibitory synapses. However, long-term synaptic plasticity, a prerequisite of memory formation, has not yet been demonstrated at these synapses. After in vitro differentiation and purification by immunoisolation, we co-cultured ES cell-derived neurons with neocortical explants, which strongly innervated the ES cell-derived target neurons. ES cell-derived neurons exhibited action potential firing similar to primary cultured neocortical neurons. The formation of glutamatergic synapses was indicated by AMPA receptor-mediated miniature excitatory postsynaptic currents (AMPA mEPSCs). In addition, a N-methyl-d-aspartate receptor-mediated, d-2-amino-5-phosphonopentanoic acid-sensitive mEPSC component was observed. We first studied activity-dependent homeostatic plasticity (synaptic scaling) of mEPSCs at glutamatergic synapses. Chronic blockade of action potential activity by TTX resulted in an increase in the amplitudes of AMPA mEPSCs. This indicates that ES cell-derived neurons are capable of a homeostatic regulation of postsynaptic AMPA receptors. In addition, we investigated neurotrophin-induced synaptic plasticity of mEPSCs at glutamatergic synapses. Chronic addition of brain-derived neurotrophic factor (BDNF; 100 ng/ml) to the culture medium resulted in an increase in both the frequency and the amplitudes of AMPA mEPSCs. These results suggest that BDNF induces the formation and/or the functional maturation of presynaptic release sites in parallel with an upregulation of postsynaptic AMPA receptors. Thus BDNF represents a potential co-factor that could improve functional synaptic integration of ES cell-derived neurons into neocortical networks.

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The Dynamics of Mammalian P Body Transport, Assembly, and Disassembly In Vivo

Molecular Biology of the Cell ◽

10.1091/mbc.e08-05-0513 ◽

2008 ◽

Vol 19 (10) ◽

pp. 4154-4166 ◽

Cited By ~ 157

Author(s):

Adva Aizer ◽

Yehuda Brody ◽

Lian Wee Ler ◽

Nahum Sonenberg ◽

Robert H. Singer ◽

...

Keyword(s):

Live Cell Imaging ◽

Cell Imaging ◽

Core Protein ◽

Dynamic Properties ◽

Single Particle Tracking ◽

Microtubule Network ◽

P Bodies ◽

Decapping Enzyme ◽

And Diffusion

Exported mRNAs are targeted for translation or can undergo degradation by several decay mechanisms. The 5′→3′ degradation machinery localizes to cytoplasmic P bodies (PBs). We followed the dynamic properties of PBs in vivo and investigated the mechanism by which PBs scan the cytoplasm. Using proteins of the decapping machinery, we asked whether PBs actively scan the cytoplasm or whether a diffusion-based mechanism is sufficient. Live-cell imaging showed that PBs were anchored mainly to microtubules. Quantitative single-particle tracking demonstrated that most PBs exhibited spatially confined motion dependent on microtubule motion, whereas stationary PB pairs were identified at the centrosome. Some PBs translocated in long-range movements on microtubules. PB mobility was compared with mitochondria, endoplasmic reticulum, peroxisomes, SMN bodies, and stress granules, and diffusion coefficients were calculated. Disruption of the microtubule network caused a significant reduction in PB mobility together with an induction of PB assembly. However, FRAP measurements showed that the dynamic flux of assembled PB components was not affected by such treatments. FRAP analysis showed that the decapping enzyme Dcp2 is a nondynamic PB core protein, whereas Dcp1 proteins continuously exchanged with the cytoplasm. This study reveals the mechanism of PB transport, and it demonstrates how PB assembly and disassembly integrate with the presence of an intact cytoskeleton.

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Molecular diversity of glutamatergic and GABAergic synapses from multiplexed fluorescence imaging

10.1101/2020.06.12.148155 ◽

2020 ◽

Author(s):

Eric Danielson ◽

Karen Perez de Arce ◽

Beth Cimini ◽

Eike-Christian Wamhoff ◽

Shantanu Singh ◽

...

Keyword(s):

Synaptic Plasticity ◽

Fluorescence Imaging ◽

Expression Profiles ◽

Molecular Organization ◽

Inhibitory Synapses ◽

Phenotypic Characterization ◽

Inhibitory Protein ◽

Gabaergic Synapses ◽

Multiplexed Fluorescence Imaging

AbstractNeuronal synapses contain hundreds of different protein species important for regulating signal transmission. Characterizing differential expression profiles of proteins within synapses in distinct regions of the brain has revealed a high degree of synaptic diversity defined by unique molecular organization. Multiplexed imaging of in vitro neuronal culture models at single synapse resolution offers new opportunities for exploring synaptic reorganization in response to chemical and genetic perturbations. Here, we combine 12-color multiplexed fluorescence imaging with quantitative image analysis and machine learning to identify novel synaptic subtypes within excitatory and inhibitory synapses based on the expression profiles of major synaptic components. We characterize differences in the correlated expression of proteins within these subtypes and we examine how the distribution of these synapses is modified following induction of synaptic plasticity. Under chronic suppression of neuronal activity, phenotypic characterization revealed coordinated increases in both excitatory and inhibitory protein levels without changes in the distribution of synaptic subtypes, suggesting concerted events targeting glutamatergic and GABAergic synapses. Our results offer molecular insight into the mechanisms of synaptic plasticity.

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