{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:51:19Z","timestamp":1773287479627,"version":"3.50.1"},"posted":{"date-parts":[[2024,5,5]]},"group-title":"Neuroscience","reference-count":85,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Mutations in\n                  <jats:italic>FGF14<\/jats:italic>\n                  , which encodes intracellular fibroblast growth factor 14 (iFGF14), have been linked to spinocerebellar ataxia type 27 (SCA27), a multisystem disorder associated with progressive deficits in motor coordination and cognitive function. Mice (\n                  <jats:italic>\n                    Fgf14\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ) lacking iFGF14 display similar phenotypes, and we have previously shown that the deficits in motor coordination reflect\n                  <jats:italic>reduced<\/jats:italic>\n                  excitability of cerebellar Purkinje neurons, owing to the loss of iFGF14-mediated regulation of the voltage-dependence of inactivation of the fast transient component of the voltage-gated Na\n                  <jats:sup>+<\/jats:sup>\n                  (Nav) current, I\n                  <jats:sub>NaT<\/jats:sub>\n                  . Here, we present the results of experiments designed to test the hypothesis that loss of iFGF14 also attenuates the intrinsic excitability of mature hippocampal and cortical pyramidal neurons. Current-clamp recordings from adult mouse hippocampal CA1 pyramidal neurons in acute\n                  <jats:italic>in vitro<\/jats:italic>\n                  slices, however, revealed that repetitive firing rates were\n                  <jats:italic>higher<\/jats:italic>\n                  in\n                  <jats:italic>\n                    Fgf14\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  , than in wild type (WT), cells. In addition, the waveforms of individual action potentials were altered in\n                  <jats:italic>\n                    Fgf14\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  hippocampal CA1 pyramidal neurons, and the loss of iFGF14 reduced the time delay between the initiation of axonal and somal action potentials. Voltage-clamp recordings revealed that the loss of iFGF14 altered the voltage-dependence of activation, but not inactivation, of I\n                  <jats:sub>NaT<\/jats:sub>\n                  in CA1 pyramidal neurons. Similar effects of the loss of iFGF14 on firing properties were evident in current-clamp recordings from layer 5 visual cortical pyramidal neurons. Additional experiments demonstrated that the loss of iFGF14\n                  <jats:italic>does not<\/jats:italic>\n                  alter the distribution of anti-Nav1.6 or anti-ankyrin G immunofluorescence labeling intensity along the axon initial segments (AIS) of mature hippocampal CA1 or layer 5 visual cortical pyramidal neurons\n                  <jats:italic>in situ<\/jats:italic>\n                  . Taken together, the results demonstrate that, in contrast with results reported for neonatal (rat) hippocampal pyramidal neurons in dissociated cell culture, the loss of iFGF14 does\n                  <jats:italic>not<\/jats:italic>\n                  disrupt AIS architecture or Nav1.6 localization\/distribution along the AIS of mature hippocampal (or cortical) pyramidal neurons\n                  <jats:italic>in situ<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2024.05.04.592532","type":"posted-content","created":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T04:25:13Z","timestamp":1714883113000},"source":"Crossref","is-referenced-by-count":3,"title":["Loss of Intracellular Fibroblast Growth Factor 14 (iFGF14)\n                  <i>Increases<\/i>\n                  the Excitability of Mature Hippocampal and Cortical Pyramidal Neurons"],"prefix":"10.64898","author":[{"given":"Joseph 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