Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular Diversity of Glutamatergic and GABAergic Synapses from Multiplexed Fluorescence Imaging.

ABSTRACT: Neuronal 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 rat primary hippocampal 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.

SUBMITTER: Danielson E

PROVIDER: S-EPMC7877457 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Precise immuno-fluorescence canceling enables highly multiplexed imaging

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-04-16 | GSE242887 | GEO

Precise immuno-fluorescence canceling enables highly multiplexed imaging [scRNA-seq]

Project description:Cell states are regulated by extrinsic signals from various external factors such as intercellular interactions, and intrinsic gene expression. Although comprehensive cell state profiling has been attempted, it remains simultaneous analysis of signal activation has still been challenging. Multiplexed imaging is a technique acquiring multiple protein information at a single cell level as traditional immunofluorescence. However, the method often compromises resolution, hindering the analysis of intracellular localization dynamics and post-translational modifications of proteins. To address these limitations, we developed an erasable fluorescence method using disulfide linkers to label antibodies. We term these antibodies ‘Precise Emission Canceling Antibodies (PECAbs)’. PECAb allows for high-resolution iterative imaging with minimal non-specific binding. Automation enables our system to achieve reproducible quantitative analysis using 206 antibodies. The resulting quantitative data allow reconstruction of the spatiotemporal dynamics of signaling pathways over both long and short timescales. Additionally, combining this approach with sequential RNA-FISH can effectively classify cells and identify their signal activation states in human tissue. Overall, the PECAb system serves as a comprehensive platform for analyzing complex cell processes, from signal transduction to gene expression.

2024-04-21 | GSE242814 | GEO

Precise immuno-fluorescence canceling enables highly multiplexed imaging [RNA-seq]

2024-04-21 | GSE242886 | GEO

Heterosynaptic scaling of developing GABAergic synapses: dependence on glutamatergic input and developmental stage.

Project description:A proportionality or balance between coactivated excitatory and inhibitory inputs is often observed for individual cortical neurons and is proposed to be important for their functions. This feature of neural circuits may arise from coordinated modulation of excitatory and inhibitory synaptic inputs, a mechanism that remains unknown. Here, in vivo whole-cell recordings from tectal neurons of young Xenopus tadpoles reveals activity-dependent bidirectional modifications of GABAergic inputs. At early developmental stages when GABAergic inputs dominate visually evoked responses, repetitive visual stimulation leads to long-term depression of GABAergic inputs. At later stages when convergent glutamatergic inputs are much stronger, long-term potentiation (LTP) of GABAergic inputs is induced. The polarity of GABAergic plasticity depends on the ratio between the magnitude of coactivated glutamatergic and GABAergic inputs (E/I ratio) to the tectal cell: LTP is induced only when the E/I ratio is above a threshold, and the level of LTP correlates linearly with the logarithm of the E/I ratio. The induction of LTP requires the activation of postsynaptic NMDA receptors, as well as presynaptic TrkB signaling likely through retrograde BDNF (brain-derived neurotrophic factor) and is achieved by overcoming a predominant depression process mediated by NMDA receptors on the presynaptic GABAergic neurons. Our results indicate that the strength of developing GABAergic synapses can be scaled in accordance to coactivated convergent glutamatergic input. This mechanism may contribute to the formation of functional neural circuits with correlated excitatory and inhibitory inputs.

| S-EPMC3232185 | biostudies-literature

Distinct circuit-dependent functions of presynaptic neurexin-3 at GABAergic and glutamatergic synapses.

Project description:?- and ?-neurexins are presynaptic cell-adhesion molecules whose general importance for synaptic transmission is well documented. The specific functions of neurexins, however, remain largely unknown because no conditional neurexin knockouts are available and targeting all ?- and ?-neurexins produced by a particular gene is challenging. Using newly generated constitutive and conditional knockout mice that target all neurexin-3? and neurexin-3? isoforms, we found that neurexin-3 was differentially required for distinct synaptic functions in different brain regions. Specifically, we found that, in cultured neurons and acute slices of the hippocampus, extracellular sequences of presynaptic neurexin-3 mediated trans-synaptic regulation of postsynaptic AMPA receptors. In cultured neurons and acute slices of the olfactory bulb, however, intracellular sequences of presynaptic neurexin-3 were selectively required for GABA release. Thus, our data indicate that neurexin-3 performs distinct essential pre- or postsynaptic functions in different brain regions by distinct mechanisms.

| S-EPMC4482778 | biostudies-literature

Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses.

Project description:Previous studies revealed that synaptotagmin 1 is the major Ca(2+) sensor for fast synchronous transmitter release at excitatory synapses. However, the molecular identity of the Ca(2+) sensor at hippocampal inhibitory synapses has not been determined. To address the functional role of synaptotagmin 1 at identified inhibitory terminals, we made paired recordings from synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus in organotypic slice cultures from wild-type and synaptotagmin 1-deficient mice. As expected, genetic elimination of synaptotagmin 1 abolished synchronous transmitter release at excitatory GC-BC synapses. However, synchronous release at inhibitory BC-GC synapses was maintained. Quantitative analysis revealed that elimination of synaptotagmin 1 reduced release probability and depression but maintained the synchrony of transmitter release at BC-GC synapses. Elimination of synaptotagmin 1 also increased the frequency of both miniature excitatory postsynaptic currents (measured in BCs) and miniature inhibitory postsynaptic currents (recorded in GCs), consistent with a clamping function of synaptotagmin 1 at both excitatory and inhibitory terminals. Single-cell reverse-transcription quantitative PCR analysis revealed that single BCs coexpressed multiple synaptotagmin isoforms, including synaptotagmin 1-5, 7, and 11-13. Our results indicate that, in contrast to excitatory synapses, synaptotagmin 1 is not absolutely required for synchronous release at inhibitory BC-GC synapses. Thus, alternative fast Ca(2+) sensors contribute to synchronous release of the inhibitory transmitter GABA in cortical circuits.

| S-EPMC2563064 | biostudies-literature

Precise immuno-fluorescence canceling enables highly multiplexed imaging

Project description:Precise immuno-fluorescence canceling enables highly multiplexed imaging

| PRJNA1015226 | ENA

Ultra-fast cycling for multiplexed cellular fluorescence imaging.

Project description:Rapid analysis of single and scant cell populations is essential in modern diagnostics, yet existing methods are often limited and slow. Here we describe an ultra-fast, highly efficient cycling method for the analysis of single cells based on unique linkers for tetrazine (Tz) / trans-cyclooctene (TCO) mediated quenching. Surprisingly, the quenching reaction rates were more than 3 orders of magnitude faster (t1/2 < 1 sec) than predicted. This allowed multi-cycle staining and immune cell profiling within an hour, leveraging the accelerated kinetics to open new diagnostic possibilities for rapid cellular analyses.

| S-EPMC8340598 | biostudies-literature

Coordinated Plasticity among Glutamatergic and GABAergic Neurons and Synapses in the Barrel Cortex Is Correlated to Learning Efficiency.

Project description:Functional plasticity at cortical synapses and neurons is presumably associated with learning and memory. Additionally, coordinated refinement between glutamatergic and GABAergic neurons occurs in associative memory. If these assumptions are present, neuronal plasticity strength and learning efficiency should be correlated. We have examined whether neuronal plasticity strength and learning efficiency are quantitatively correlated in a mouse model of associative learning. Paired whisker and odor stimulations in mice induce odorant-induced whisker motions. The fully establishment of this associative memory appears fast and slow, which are termed as high learning efficiency and low learning efficiency, respectively. In the study of cellular mechanisms underlying this differential learning efficiency, we have compared the strength of neuronal plasticity in the barrel cortices that store associative signals from the mice with high vs. low learning efficiencies. Our results indicate that the levels of learning efficiency are linearly correlated with the upregulated strengths of excitatory synaptic transmission on glutamatergic neurons and their excitability, as well as the downregulated strengths of GABAergic neurons' excitability, their excitatory synaptic inputs and inhibitory synaptic outputs in layers II~III of barrel cortices. The correlations between learning efficiency in associative memory formation and coordinated plasticity at cortical glutamatergic and GABAergic neurons support the notion that the plasticity of associative memory cells is a basis for memory strength.

| S-EPMC5526921 | biostudies-literature

Metaplasticity at single glutamatergic synapses.

Project description:Optimal function of neuronal networks requires interplay between rapid forms of Hebbian plasticity and homeostatic mechanisms that adjust the threshold for plasticity, termed metaplasticity. Numerous forms of rapid synapse plasticity have been examined in detail. However, the rules that govern synaptic metaplasticity are much less clear. Here, we demonstrate a local subunit-specific switch in NMDA receptors that alternately primes or prevents potentiation at single synapses. Prolonged suppression of neurotransmitter release enhances NMDA receptor currents, increases the number of functional NMDA receptors containing NR2B, and augments calcium transients at single dendritic spines. This local switch in NMDA receptors requires spontaneous glutamate release but is independent of action potentials. Moreover, single inactivated synapses exhibit a lower induction threshold for both long-term synaptic potentiation and plasticity-induced spine growth. Thus, spontaneous glutamate release adjusts plasticity threshold at single synapses by local regulation of NMDA receptors, providing a novel spatially delimited form of synaptic metaplasticity.

| S-EPMC2911980 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data