Membrane lipids and their metabolism have key functions in neurotransmission. Here we provide a quantitative lipid inventory of mouse and rat synaptic junctions. To this end, we developed a multiomics extraction and analysis workflow to probe the interplay of proteins and lipids in synaptic signal transduction from the same sample. Based on this workflow, we generate hypotheses about novel mechanisms underlying complex changes in synaptic connectivity elicited by environmental stimuli. As a proof of principle, this approach reveals that in mice exposed to an enriched environment, reduced endocannabinoid synthesis and signaling is linked to increased surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in a subset of Cannabinoid-receptor 1 positive synapses. This mechanism regulates synaptic strength in an input-specific manner. Thus, we establish a compartment-specific multiomics workflow that is suitable to extract information from complex lipid and protein networks involved in synaptic function and plasticity.
- MeSH
- amidohydrolasy metabolismus MeSH
- AMPA receptory metabolismus MeSH
- endokanabinoidy metabolismus MeSH
- hipokampus cytologie metabolismus MeSH
- krysa rodu rattus MeSH
- lipidy analýza MeSH
- metabolismus lipidů * genetika MeSH
- monoacylglycerollipasy metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- potkani Wistar MeSH
- proteom analýza MeSH
- proteomika metody MeSH
- signální transdukce * genetika MeSH
- synapse metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
