Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity
Abstract Understanding the mechanisms of synaptic plasticity is crucial for elucidating how the brain adapts to internal and external stimuli. A key objective of plasticity is maintaining physiological activity states during perturbations by adjusting synaptic transmission through negative feedback...
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2024-11-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-024-01153-y |
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| author | Maximilian Lenz Paul Turko Pia Kruse Amelie Eichler Zhuo Angel Chen Juri Rappsilber Imre Vida Andreas Vlachos |
| author_facet | Maximilian Lenz Paul Turko Pia Kruse Amelie Eichler Zhuo Angel Chen Juri Rappsilber Imre Vida Andreas Vlachos |
| author_sort | Maximilian Lenz |
| collection | DOAJ |
| description | Abstract Understanding the mechanisms of synaptic plasticity is crucial for elucidating how the brain adapts to internal and external stimuli. A key objective of plasticity is maintaining physiological activity states during perturbations by adjusting synaptic transmission through negative feedback mechanisms. However, identifying and characterizing novel molecular targets orchestrating synaptic plasticity remains a significant challenge. This study investigated the effects of tetrodotoxin (TTX)-induced synaptic plasticity within organotypic entorhino-hippocampal tissue cultures, offering insights into the functional, transcriptomic, and proteomic changes associated with network inhibition via voltage-gated sodium channel blockade. Our experiments demonstrate that TTX treatment induces substantial functional plasticity of excitatory synapses, as evidenced by increased miniature excitatory postsynaptic current (mEPSC) amplitudes and frequencies in both dentate granule cells and CA1 pyramidal neurons. Correlating transcriptomic and proteomic data, we identified novel targets for future research into homeostatic plasticity, including cytoglobin, SLIT-ROBO Rho GTPase Activating Protein 3, Transferrin receptor, and 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. These data provide a valuable resource for future studies aiming to understand the orchestration of homeostatic plasticity by metabolic pathways in distinct cell types of the central nervous system. |
| format | Article |
| id | doaj-art-27934baf442b403783f2185ea8c3d639 |
| institution | DOAJ |
| issn | 1756-6606 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
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| series | Molecular Brain |
| spelling | doaj-art-27934baf442b403783f2185ea8c3d6392025-08-20T02:49:59ZengBMCMolecular Brain1756-66062024-11-011711910.1186/s13041-024-01153-yTranscriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticityMaximilian Lenz0Paul Turko1Pia Kruse2Amelie Eichler3Zhuo Angel Chen4Juri Rappsilber5Imre Vida6Andreas Vlachos7Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgInstitute of Integrative Neuroanatomy and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin BerlinDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgChair of Bioanalytics, Technische Universität BerlinChair of Bioanalytics, Technische Universität BerlinInstitute of Integrative Neuroanatomy and NeuroCure Cluster of Excellence, Charité-Universitätsmedizin BerlinDepartment of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of FreiburgAbstract Understanding the mechanisms of synaptic plasticity is crucial for elucidating how the brain adapts to internal and external stimuli. A key objective of plasticity is maintaining physiological activity states during perturbations by adjusting synaptic transmission through negative feedback mechanisms. However, identifying and characterizing novel molecular targets orchestrating synaptic plasticity remains a significant challenge. This study investigated the effects of tetrodotoxin (TTX)-induced synaptic plasticity within organotypic entorhino-hippocampal tissue cultures, offering insights into the functional, transcriptomic, and proteomic changes associated with network inhibition via voltage-gated sodium channel blockade. Our experiments demonstrate that TTX treatment induces substantial functional plasticity of excitatory synapses, as evidenced by increased miniature excitatory postsynaptic current (mEPSC) amplitudes and frequencies in both dentate granule cells and CA1 pyramidal neurons. Correlating transcriptomic and proteomic data, we identified novel targets for future research into homeostatic plasticity, including cytoglobin, SLIT-ROBO Rho GTPase Activating Protein 3, Transferrin receptor, and 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. These data provide a valuable resource for future studies aiming to understand the orchestration of homeostatic plasticity by metabolic pathways in distinct cell types of the central nervous system.https://doi.org/10.1186/s13041-024-01153-yhomeostatic synaptic plasticityorganotypic tissue culturetranscriptomeproteomics |
| spellingShingle | Maximilian Lenz Paul Turko Pia Kruse Amelie Eichler Zhuo Angel Chen Juri Rappsilber Imre Vida Andreas Vlachos Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity Molecular Brain homeostatic synaptic plasticity organotypic tissue culture transcriptome proteomics |
| title | Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity |
| title_full | Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity |
| title_fullStr | Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity |
| title_full_unstemmed | Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity |
| title_short | Transcriptomic and de novo proteomic analyses of organotypic entorhino-hippocampal tissue cultures reveal changes in metabolic and signaling regulators in TTX-induced synaptic plasticity |
| title_sort | transcriptomic and de novo proteomic analyses of organotypic entorhino hippocampal tissue cultures reveal changes in metabolic and signaling regulators in ttx induced synaptic plasticity |
| topic | homeostatic synaptic plasticity organotypic tissue culture transcriptome proteomics |
| url | https://doi.org/10.1186/s13041-024-01153-y |
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