{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:40:50Z","timestamp":1776494450475,"version":"3.51.2"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Belle S. and Irving E. Meller Center for the Biology of Aging"},{"name":"Adelis Brain Research Award"},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","award":["2113\/19"],"award-info":[{"award-number":["2113\/19"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004412","name":"Human Frontier Science Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004412","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Research Council","award":["ERC-CoG 101001226"],"award-info":[{"award-number":["ERC-CoG 101001226"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Applying information theoretic measures to neuronal activity data enables the quantification of neuronal encoding quality. However, when the sample size is limited, a na\u00efve estimation of the information content typically contains a systematic overestimation (upward bias), which may lead to misinterpretation of coding characteristics. This bias is exacerbated in Ca<jats:sup>2+<\/jats:sup> imaging because of the temporal sparsity of elevated Ca<jats:sup>2+<\/jats:sup> signals. Here, we introduce methods to correct for the bias in the na\u00efve estimation of information content from limited sample sizes and temporally sparse neuronal activity. We demonstrate the higher accuracy of our methods over previous ones, when applied to Ca<jats:sup>2+<\/jats:sup> imaging data recorded from the mouse hippocampus and primary visual cortex, as well as to simulated data with matching tuning properties and firing statistics. Our bias-correction methods allowed an accurate estimation of the information place cells carry about the animal\u2019s position (<jats:italic>spatial information<\/jats:italic>) and uncovered the spatial resolution of hippocampal coding. Furthermore, using our methods, we found that cells with higher peak firing rates carry higher spatial information per spike and exposed differences between distinct hippocampal subfields in the long-term evolution of the spatial code. These results could be masked by the bias when applying the commonly used na\u00efve calculation of information content. Thus, a bias-free estimation of information content can uncover otherwise overlooked properties of the neural code.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009832","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T18:32:21Z","timestamp":1644604341000},"page":"e1009832","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Bias-free estimation of information content in temporally sparse neuronal activity"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4245-5786","authenticated-orcid":true,"given":"Liron","family":"Sheintuch","sequence":"first","affiliation":[]},{"given":"Alon","family":"Rubin","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6658-9303","authenticated-orcid":true,"given":"Yaniv","family":"Ziv","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"issue":"3","key":"pcbi.1009832.ref001","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nn.3329","article-title":"Long-term dynamics of CA1 hippocampal place codes","volume":"16","author":"Y Ziv","year":"2013","journal-title":"Nat Neurosci"},{"issue":"10","key":"pcbi.1009832.ref002","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/nmeth.1694","article-title":"Miniaturized integration of a fluorescence microscope.","volume":"8","author":"KK Ghosh","year":"2011","journal-title":"Nat Methods."},{"issue":"7458","key":"pcbi.1009832.ref003","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature12354","article-title":"Ultrasensitive fluorescent proteins for imaging neuronal activity","volume":"499","author":"TW Chen","year":"2013","journal-title":"Nature"},{"issue":"4","key":"pcbi.1009832.ref004","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.celrep.2017.10.013","article-title":"Tracking the same neurons across multiple days in Ca2+ imaging data","volume":"21","author":"L Sheintuch","year":"2017","journal-title":"Cell Rep"},{"issue":"7","key":"pcbi.1009832.ref005","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1162\/089976698300017115","article-title":"Mutual Information, Fisher Information, and Population Coding.","volume":"10","author":"N Brunel","year":"1998","journal-title":"Neural Comput."},{"key":"pcbi.1009832.ref006","volume-title":"Spikes: exploring the neural code","author":"F. 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