{"article_type":"original","oa":1,"date_published":"2025-09-27T00:00:00Z","doi":"10.1113/JP288183","publication_identifier":{"eissn":["1469-7793"],"issn":["0022-3751"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection","acknowledgement":"This work was supported by Biological Services teams at both the Laboratory of Molecular Biology and Ares facilities. The authors are very grateful to Prof. Helmut Kessels and Dr. Hinze Ho for initial discussions that led to this study, Dr. Andrew Penn for constructive feedback on the project, Xinyao Dou for comments on the study, and Profs. Peter Jonas and Roger Nicoll for feedback on the manuscript. Funding was provided by the Medical Research Council (MRC – MC_U105174197 to I.H.G.) and the European Union's Horizon 2020 programme through a Marie Skłodowska-Curie Actions Individual Fellowship (MSCA-IF 101026635 to J.F.W.).","project":[{"call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"}],"date_updated":"2025-10-13T06:28:33Z","scopus_import":"1","citation":{"ama":"Greger IH, Watson J. ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection. Journal of Physiology. 2025. doi:10.1113/JP288183","ista":"Greger IH, Watson J. 2025. ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection. Journal of Physiology.","short":"I.H. Greger, J. Watson, Journal of Physiology (2025).","mla":"Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes in Synaptic Properties Due to Incomplete Event Detection.” Journal of Physiology, Wiley, 2025, doi:10.1113/JP288183.","ieee":"I. H. Greger and J. Watson, “‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection,” Journal of Physiology. Wiley, 2025.","chicago":"Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes in Synaptic Properties Due to Incomplete Event Detection.” Journal of Physiology. Wiley, 2025. https://doi.org/10.1113/JP288183.","apa":"Greger, I. H., & Watson, J. (2025). ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete event detection. Journal of Physiology. Wiley. https://doi.org/10.1113/JP288183"},"ec_funded":1,"external_id":{"pmid":["41015537"]},"oa_version":"Published Version","article_processing_charge":"Yes (in subscription journal)","quality_controlled":"1","language":[{"iso":"eng"}],"OA_type":"hybrid","publication_status":"epub_ahead","status":"public","publication":"Journal of Physiology","corr_author":"1","_id":"20457","OA_place":"publisher","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1113/JP288183"}],"date_created":"2025-10-12T22:01:27Z","author":[{"last_name":"Greger","full_name":"Greger, Ingo H.","first_name":"Ingo H."},{"first_name":"Jake","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson"}],"year":"2025","abstract":[{"text":"Patch-clamp recording of miniature postsynaptic currents (mPSCs, or ‘minis’) is used extensively to investigate the functional properties of synapses. With this approach, spontaneous synaptic transmission events are recorded in an attempt to determine quantal synaptic parameters or the effect of synaptic manipulations. However, at the majority of brain synapses these events are small, with many undetectable due to recording noise. The effects of incomplete detection were well appreciated in the early years of synaptic physiology analysis, but appear to be increasingly forgotten. Here we sought to characterise the consequences of incomplete detection on the interpretability of mini analysis, using simulated mPSC data to give full control over event parameters. We demonstrate that commonly reported measures such as mean event amplitude and frequency, are misrepresented by the loss of undetected events. Probabilistic loss of small events results in detected event amplitude distributions that appear biologically complete, yet do not reflect the underlying synaptic properties. With both simulated and experimental datasets, we demonstrate that specific changes in event amplitude are primarily detected as changes in frequency, compromising classical biological interpretations. To facilitate more robust data analysis and interpretation, we detail a means for experimental estimation of the event detection limit and provide practical recommendations for data analysis. Together, our study highlights how mini analysis is prone to falsely reporting synaptic changes, raising awareness of these considerations, and provides a framework for more robust data analysis and interpretation.","lang":"eng"}],"pmid":1,"PlanS_conform":"1","department":[{"_id":"PeJo"}],"related_material":{"link":[{"url":"https://github.com/jakefwatson/miniplace","relation":"software"}]},"publisher":"Wiley","month":"09","day":"27","type":"journal_article"}