{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:04:53Z","timestamp":1789509893796,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,11]]},"group-title":"Neuroscience","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Brain microRNA (miRNA) expression can shift in response to the social environment, translating external cues into regulatory action that can influence brain structure, neural activity, and behavior. miRNAs are key drivers of behavioral flexibility, regulating gene networks involved in neuroplasticity. We manipulated social rearing conditions of brilliant-thighed poison frog tadpoles (\n                  <jats:italic>Allobates femoralis<\/jats:italic>\n                  ) to test whether isolation-linked behavioral changes are associated with altered miRNA expression in the midbrain and eyes, tissues linked by the retinotectal tract, a known connection for trafficked precursor miRNAs. We asked whether isolation alters visually guided behavior using a light\/dark preference assay and found that isolated tadpoles spent less of the trial on the dark side than did group-housed tadpoles. In a social place preference assay, group-housed tadpoles preferred a zone near a conspecific over an object control when provided with multimodal sensory access, but not when access was restricted to vision alone. We next tested whether social rearing conditions influenced miRNA expression and found that isolated tadpoles exhibited upregulation of miR-15-P1c_3p*, the canonically non-dominant arm of an understudied miRNA, in the midbrain and eyes. We detected a shift in arm dosing for miR-124, a miRNA with conserved roles in neural differentiation and plasticity. Finally, social isolation during development was associated with downregulation of parathyroid hormone 2 (\n                  <jats:italic>pth2<\/jats:italic>\n                  ), a peptide associated with social isolation and mechanosensation in other aquatic larvae. This work contributes to a growing body of literature implicating miRNAs in developmental neuroplasticity, presenting precedented and novel signatures of the transcriptional and regulatory response to isolation.\n                <\/jats:p>","DOI":"10.64898\/2026.09.04.749321","type":"posted-content","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:00:16Z","timestamp":1789164016000},"source":"Crossref","is-referenced-by-count":0,"title":["Social isolation is associated with microRNA expression changes in the visual system of poison frog tadpoles"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2136-8184","authenticated-orcid":false,"given":"Neil M.","family":"Khosla","sequence":"first","affiliation":[{"name":"Stanford University, Department of Biology, 371 Jane Stanford Way, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7973-6364","authenticated-orcid":false,"given":"Max M.","family":"Madrzyk","sequence":"additional","affiliation":[{"name":"Stanford University, Department of Biology, 371 Jane Stanford Way, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8054-6049","authenticated-orcid":false,"given":"Keira","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Stanford University, Department of Biology, 371 Jane Stanford Way, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Li Gallardo","family":"Palmeri","sequence":"additional","affiliation":[{"name":"Stanford University, Department of Biology, 371 Jane Stanford Way, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Butler","sequence":"additional","affiliation":[{"name":"Stanford University, Department of Biology, 371 Jane Stanford Way, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-4077","authenticated-orcid":false,"given":"Lauren A.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Stanford University, Department of Biology, 371 Jane Stanford Way, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091514451228000_2026.09.04.749321v1.1","unstructured":"Adebogun, G. T. , Bachmann, A. E. , Callan, A. A. , Khan, U. , Lewis, A. R. , Pollock, A. C. , Alfonso, S. A. , Arango Sumano, D. , Bhatt, D. A. , Cullen, A. B. , et al. (2023). Albino Xenopus laevis tadpoles prefer dark environments compared to wild type. MicroPubl Biol 2023,."},{"key":"2026091514451228000_2026.09.04.749321v1.2","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41586-020-2988-z","article-title":"The neuropeptide Pth2 dynamically senses others via mechanosensation","volume":"588","year":"2020","journal-title":"Nature"},{"key":"2026091514451228000_2026.09.04.749321v1.3","doi-asserted-by":"crossref","first-page":"103868","DOI":"10.1016\/j.isci.2022.103868","article-title":"The neuropeptide Pth2 modulates social behavior and anxiety in zebrafish","volume":"25","year":"2022","journal-title":"iScience"},{"key":"2026091514451228000_2026.09.04.749321v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac363"},{"key":"2026091514451228000_2026.09.04.749321v1.5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.bbr.2017.03.010","article-title":"Hippocampal BDNF overexpression or microR124a silencing reduces anxiety- and autism-like behaviors in rats","volume":"326","year":"2017","journal-title":"Behavioural Brain Research"},{"key":"2026091514451228000_2026.09.04.749321v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"2026091514451228000_2026.09.04.749321v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2979"},{"key":"2026091514451228000_2026.09.04.749321v1.8","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-10-0439"},{"key":"2026091514451228000_2026.09.04.749321v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01274-3"},{"key":"2026091514451228000_2026.09.04.749321v1.10","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1098\/rsbl.2008.0591","article-title":"Tactical reproductive parasitism via larval cannibalism in Peruvian poison frogs","volume":"5","year":"2009","journal-title":"Biol. Lett"},{"key":"2026091514451228000_2026.09.04.749321v1.11","doi-asserted-by":"crossref","unstructured":"Butler, J. M. and O\u2019Connell, L. A . (2023). A simple phototaxis assay for aquatic larvae v1.","DOI":"10.17504\/protocols.io.x54v9p294g3e\/v1"},{"key":"2026091514451228000_2026.09.04.749321v1.12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ydbio.2024.05.006","article-title":"Tadpoles rely on mechanosensory stimuli for communication when visual capabilities are poor","volume":"514","year":"2024","journal-title":"Developmental Biology"},{"key":"2026091514451228000_2026.09.04.749321v1.13","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.omtn.2020.05.001","article-title":"MicroRNA-206 Regulates Stress-Provoked Aggressive Behaviors in Post-weaning Social Isolation Mice","volume":"20","year":"2020","journal-title":"Molecular Therapy - Nucleic Acids"},{"key":"2026091514451228000_2026.09.04.749321v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1094"},{"key":"2026091514451228000_2026.09.04.749321v1.15","doi-asserted-by":"crossref","first-page":"EMBJ2019102513","DOI":"10.15252\/embj.2019102513","article-title":"Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits","volume":"39","year":"2020","journal-title":"EMBO J"},{"key":"2026091514451228000_2026.09.04.749321v1.16","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2026091514451228000_2026.09.04.749321v1.17","doi-asserted-by":"crossref","unstructured":"Dobolyi, A. , Dimitrov, E. , Palkovits, M. and Usdin, T. B. (2012). The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor. Front. Endocrin. 3,.","DOI":"10.3389\/fendo.2012.00121"},{"key":"2026091514451228000_2026.09.04.749321v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.08.023"},{"key":"2026091514451228000_2026.09.04.749321v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.07.051"},{"key":"2026091514451228000_2026.09.04.749321v1.20","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.160721"},{"key":"2026091514451228000_2026.09.04.749321v1.21","doi-asserted-by":"crossref","first-page":"jeb245822","DOI":"10.1242\/jeb.245822","article-title":"Visual environment of rearing sites affects larval response to perceived risk in poison frogs","volume":"226","year":"2023","journal-title":"Journal of Experimental Biology"},{"key":"2026091514451228000_2026.09.04.749321v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1950"},{"key":"2026091514451228000_2026.09.04.749321v1.23","first-page":"183","volume":"16","year":"1960","journal-title":"A simplified table for staging anuran embryos and larvae with notes on identification"},{"key":"2026091514451228000_2026.09.04.749321v1.24","doi-asserted-by":"publisher","DOI":"10.1093\/sysbio\/syaa034"},{"key":"2026091514451228000_2026.09.04.749321v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00809-6"},{"key":"2026091514451228000_2026.09.04.749321v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01443-0"},{"key":"2026091514451228000_2026.09.04.749321v1.27","doi-asserted-by":"publisher","DOI":"10.1186\/1748-7188-6-26"},{"key":"2026091514451228000_2026.09.04.749321v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026091514451228000_2026.09.04.749321v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0209-y"},{"key":"2026091514451228000_2026.09.04.749321v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.225"},{"key":"2026091514451228000_2026.09.04.749321v1.31","doi-asserted-by":"crossref","first-page":"arag041","DOI":"10.1093\/beheco\/arag041","article-title":"Predation risk shapes among- and within-individual variation in behavior in poison frog tadpoles","volume":"37","year":"2026","journal-title":"Behavioral Ecology"},{"key":"2026091514451228000_2026.09.04.749321v1.32","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0102"},{"key":"2026091514451228000_2026.09.04.749321v1.33","doi-asserted-by":"crossref","unstructured":"Nakamura, K. , Khosla, N. , Madrzyk, M. and O\u2019Connell, L. (2024). 3D-printed social place preference assays for aquatic larvae v1.","DOI":"10.17504\/protocols.io.bp2l6d4y5vqe\/v1"},{"key":"2026091514451228000_2026.09.04.749321v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2020.104869"},{"key":"2026091514451228000_2026.09.04.749321v1.35","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0788-1"},{"key":"2026091514451228000_2026.09.04.749321v1.36","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13041-015-0128-8","article-title":"Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety","volume":"8","year":"2015","journal-title":"Mol Brain"},{"key":"2026091514451228000_2026.09.04.749321v1.37","doi-asserted-by":"crossref","first-page":"105037","DOI":"10.1016\/j.neubiorev.2023.105037","article-title":"Play fighting and the development of the social brain: The rat\u2019s tale","volume":"145","year":"2023","journal-title":"Neuroscience & Biobehavioral Reviews"},{"key":"2026091514451228000_2026.09.04.749321v1.38","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00018-025-05663-3","article-title":"Decoding microRNA arm switching: a key to evolutionary innovation and gene regulation","volume":"82","year":"2025","journal-title":"Cell. Mol. Life Sci"},{"key":"2026091514451228000_2026.09.04.749321v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.05.029"},{"key":"2026091514451228000_2026.09.04.749321v1.40","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s41419-018-0732-5","article-title":"The distinct role of strand-specific miR-514b-3p and miR-514b-5p in colorectal cancer metastasis","volume":"9","year":"2018","journal-title":"Cell Death Dis"},{"key":"2026091514451228000_2026.09.04.749321v1.41","doi-asserted-by":"publisher","DOI":"10.1186\/1742-9994-10-67"},{"key":"2026091514451228000_2026.09.04.749321v1.42","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/beheco\/arv069","article-title":"Flexible compensation of uniparental care: female poison frogs take over when males disappear","volume":"26","year":"2015","journal-title":"BEHECO"},{"key":"2026091514451228000_2026.09.04.749321v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.175"},{"key":"2026091514451228000_2026.09.04.749321v1.44","doi-asserted-by":"crossref","first-page":"jeb243122","DOI":"10.1242\/jeb.243122","article-title":"Tadpole-transporting frogs use stagnant water odor to find pools in the rainforest","volume":"224","year":"2021","journal-title":"Journal of Experimental Biology"},{"key":"2026091514451228000_2026.09.04.749321v1.45","doi-asserted-by":"publisher","DOI":"10.1002\/dev.21581"},{"key":"2026091514451228000_2026.09.04.749321v1.46","doi-asserted-by":"crossref","unstructured":"Stephens, M . (2016). False discovery rates: a new deal. Biostat kxw 041.","DOI":"10.1093\/biostatistics\/kxw041"},{"key":"2026091514451228000_2026.09.04.749321v1.47","doi-asserted-by":"crossref","unstructured":"Sun, Y. , Luo, Z.-M. , Guo, X.-M. , Su, D.-F. and Liu, X . (2015). An updated role of microRNA-124 in central nervous system disorders: a review. Front. Cell. Neurosci. 9,.","DOI":"10.3389\/fncel.2015.00193"},{"key":"2026091514451228000_2026.09.04.749321v1.48","doi-asserted-by":"crossref","first-page":"jeb243647","DOI":"10.1242\/jeb.243647","article-title":"Naive poison frog tadpoles use bi-modal cues to avoid insect predators but not heterospecific predatory tadpoles","volume":"224","year":"2021","journal-title":"Journal of Experimental Biology"},{"key":"2026091514451228000_2026.09.04.749321v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2022.07.009"},{"key":"2026091514451228000_2026.09.04.749321v1.50","doi-asserted-by":"crossref","first-page":"100348","DOI":"10.1016\/j.xgen.2023.100348","article-title":"Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine","volume":"3","year":"2023","journal-title":"Cell Genomics"},{"key":"2026091514451228000_2026.09.04.749321v1.51","doi-asserted-by":"crossref","unstructured":"Viczian, A. S. and Zuber, M. E. (2014). A Simple Behavioral Assay for Testing Visual Function in Xenopus laevis. JoVE 51726.","DOI":"10.3791\/51726-v"},{"key":"2026091514451228000_2026.09.04.749321v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0695-6"},{"key":"2026091514451228000_2026.09.04.749321v1.53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004206"},{"key":"2026091514451228000_2026.09.04.749321v1.54","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1038\/s41467-019-12292-5","article-title":"microRNA arm-imbalance in part from complementary targets mediated decay promotes gastric cancer progression","volume":"10","year":"2019","journal-title":"Nat Commun"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.04.749321","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:45:24Z","timestamp":1789508724000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.04.749321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":54,"URL":"https:\/\/doi.org\/10.64898\/2026.09.04.749321","relation":{},"subject":[],"published":{"date-parts":[[2026,9,11]]},"subtype":"preprint"}}