{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:56:06Z","timestamp":1785426966127,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,4]]},"group-title":"Neuroscience","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Dana Foundation David Mahoney Neuroimaging Program"},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS088555"],"award-info":[{"award-number":["R01NS088555"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["RF1NS088555"],"award-info":[{"award-number":["RF1NS088555"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["T32NS077889"],"award-info":[{"award-number":["T32NS077889"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["NS102417"],"award-info":[{"award-number":["NS102417"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"award":["5T32AI005284-40"],"award-info":[{"award-number":["5T32AI005284-40"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"crossref","award":["R01DA041513"],"award-info":[{"award-number":["R01DA041513"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  B cells infiltrate the contralesional hippocampus following stroke, but whether lymphocytes modulate post-stroke plasticity and neuronal network function remains unknown. To identify immune cell mechanism(s) supporting remote plasticity, we examined the impact of B cell depletion on synaptic and neuronal activity in the hippocampal circuit following stroke. Basal synaptic transmission in the contralesional dentate gyrus (DG) following a stroke in adult male mice was decreased with B cell depletion. Expanding our studies to encompass the CA1 and DG regions of the hippocampal circuit in male and female mice of different ages, we utilized synapsin-Cre\/GCaMP6s mice to visualize spontaneous calcium activity during a 3-week B cell depletion with and without prior stroke. Systemic B cell depletion in the absence of injury altered neuronal activity in the DG, suggesting a novel neuromodulatory role for circulating immune cells. Stroke increased Ca\n                  <jats:sup>2+<\/jats:sup>\n                  transient amplitudes in the contralesional DG and CA1, with B cell depletion again reducing DG amplitudes while increasing the frequency of Ca\n                  <jats:sup>2+<\/jats:sup>\n                  transients. Robust linear regression revealed significant main effects and higher-order interactions (depletion\u00d7sex\u00d7age\u00d7injury), including increased Ca\n                  <jats:sup>2+<\/jats:sup>\n                  transient amplitudes in older post-stroke mice lowered by systemic B cell depletion, though overall the DG appears more sensitive to modulation versus CA1. These results suggest that circulating B cells can tune hippocampal network activity dependent on age, sex, and the presence of brain injury. The selective vulnerability of the DG to depletion-age-injury interactions opens an avenue for future studies on region-specific neuroimmune crosstalk during post-stroke cognitive recovery.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>\n                    Presubmission inquiry for\n                    <jats:italic>Neuron<\/jats:italic>\n                  <\/jats:title>\n                  <jats:p>We uncover crucial insights on the capacity of circulating B cells to directly modulate hippocampal network activity, showing that B cells are not just passive players, but active neuromodulators whose effects are dependent on sex, age, and stroke injury status. In fact, B cells are central players to functional recovery whose evolving role shifts over time, from acutely beneficial and neurotrophic to chronically maladaptive, depending on timing, context, and responding B cell subset. Our study demonstrates a mechanistic link between systemic immune modulation and neuronal calcium activity. This integrative perspective aligns with Neuron\u2019s mission to publish studies that link cellular processes to systems-level functions. These novel findings also add to a more unified model of neuro-immune interactions that highlights how immunotherapies could be harnessed to improve neuronal function during stroke and aging, with several FDA-approved immunotherapeutics available to modulate systemic adaptive immune responses.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.03.02.709034","type":"posted-content","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T19:10:29Z","timestamp":1772651429000},"source":"Crossref","is-referenced-by-count":0,"title":["Peripheral B cell populations tune spontaneous neuronal activity in the uninjured hippocampus after stroke"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8512-8369","authenticated-orcid":false,"given":"Thomas A.","family":"Ujas","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Kentucky, Lexington, Kentucky, 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