{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:57:24Z","timestamp":1790521044542,"version":"4.1.0"},"reference-count":57,"publisher":"Society for Neuroscience","issue":"9","license":[{"start":{"date-parts":[[2027,3,1]],"date-time":"2027-03-01T00:00:00Z","timestamp":1803859200000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"name":"HHS | National Institutes of Health","award":["NS078152"],"award-info":[{"award-number":["NS078152"]}]}],"content-domain":{"domain":["eneuro.org"],"crossmark-restriction":true},"short-container-title":["eNeuro"],"accepted":{"date-parts":[[2026,8,5]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    The large-conductance, Ca\u00b2\n                    <jats:sup>+<\/jats:sup>\n                    - and voltage-activated K\n                    <jats:sup>+<\/jats:sup>\n                    (BK) channels are widely distributed in the central nervous system, where they play diverse roles in regulating brain activity. The \u03b31 (LRRC26) subunit functions as a potent activator of BK channels, inducing a large shift in the voltage dependence of channel activation toward the hyperpolarized direction. Given the large conductance of BK channels, their activators have therapeutic potential for various diseases. To investigate the impact of activator-induced hyperactivity of BK channels on brain function, we generated conditional hLRRC26 transgenic mice in which recombinant human LRRC26 is expressed in the forebrain under the control of the CaMKII\u03b1 promoter and the tetracycline Tet-Off system. Experiments included mice of both sexes and data were pooled, as no obvious sex-dependent effects were detected. Histological analysis following postweaning doxycycline withdrawal confirmed hLRRC26 expression in the forebrain, with strong expression in the hippocampus, isocortex, and striatum. Behavioral tests demonstrated that long-term hLRRC26 expression resulted in locomotor hyperactivity, cognitive deficits, and some anxiety- and depression-like behaviors. At 2\u20134 months of age, hLRRC26 transgenic mice exhibited significantly elevated locomotor activity, with increased movement distance in the open-field test, despite shorter strides in the footprint test. These mice also showed impaired learning performance in the water maze, novel object recognition, and rotarod tests compared with controls. At 12\u201314 months, transgenic mice continued to display locomotor hyperactivity and cognitive deficits. In conclusion, hLRRC26 transgenic mice demonstrated heightened locomotor activity and cognitive impairments, revealing potential ADHD-like neurological consequences of BK channel hyperactivity.\n                  <\/jats:p>","DOI":"10.1523\/eneuro.0053-25.2026","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:50:22Z","timestamp":1788889822000},"page":"ENEURO.0053-25.2026","update-policy":"https:\/\/doi.org\/10.1523\/eneuro.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Transgenic Expression of BK Channel Auxiliary LRRC26 Subunit in the Forebrain Causes Locomotor Hyperactivity and Cognitive 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