{"database":"bioimages","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Philip J. Dittmer, PhD"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-BIAD3188"],"repository":["bioimages"],"additional_accession":["39178228"],"figure_sub":["Specimen","Image analysis","Funding","Study Component","Biosample","organisation","Image correlation","Associations","Annotation","Image acquisition"],"pubmed_authors":["Philip J. Dittmer, PhD"]},"is_claimable":false,"name":"L-type Ca2+ channel activation of STIM1–Orai1 signaling remodels the dendritic spine ER to maintain long-term structural plasticity","description":"Our recent research, published in PNAS in 2024, highlights the significant role of the endoplasmic reticulum (ER) in modulating activity-driven postsynaptic signaling events. This signaling is associated with long-term potentiation of dendritic spine size, known as structural long-term potentiation (sLTP), which underpins the functional strengthening of glutamatergic synaptic transmission. Our findings demonstrate that high-frequency optical glutamate uncaging (HFGU) induces long-lasting sLTP in most ER-containing (ER+) spines, resulting in a sustained increase in spine ER content. This process is driven by a signaling cascade initiated by N-methyl-D-aspartate receptors (NMDARs), L-type Ca2+ channels (LTCCs), and Orai1 channels, the latter of which are activated by stromal interaction molecule 1 (STIM1) in response to Ca2+ release from the ER. In contrast, HFGU stimulation of ER-lacking (ER−) spines results in only transient sLTP and diminished Ca2+ signals, notably lacking contributions from Orai1 and the ER. Supporting the notion that spine ER governs structural metaplasticity, delivering a well-timed second HFGU stimulus to ER− spines recruited ER and produced persistent sLTP. However, repeated stimulation of previously potentiated ER+ spines failed to further enhance Ca2+ signaling, spine size, or spine ER content, potentially serving as a protective mechanism against runaway potentiation. Through our exploration of the distinct inhibitory effects of Orai1 inhibitors, AnCoA4 and Synta66, we found that the physical interaction between STIM1 and Orai1 at ER-plasma membrane junctions, rather than the subsequent Ca2+ entry, is essential for the persistence of sLTP.","dates":{"release":"2026-04-30T00:00:00Z","modification":"2026-04-30T01:02:01.299Z","creation":"2026-04-20T21:53:08.708Z"},"accession":"S-BIAD3188","cross_references":{}}