{
 "paper": "wengert-2026-kcnc1",
 "model": "supplied:runs/wengert-2026-kcnc1/plain-claim.answer.json",
 "prompt": "extract/prompts/plain-claim.md",
 "claims": [
  {
   "slug": "a421v-kv31-membrane-trafficking-impaired",
   "role": "empirical",
   "panel": "fig3H, fig3I",
   "plain": "In juvenile Kcnc1-A421V mice, less Kv3.1 reaches the surface of parvalbumin interneurons and more of it stays inside the cell."
  },
  {
   "slug": "a421v-mice-die-before-122d",
   "role": "empirical",
   "panel": "fig1",
   "plain": "Every Kcnc1-A421V mouse dies before 122 days of age, while wild-type littermates live on."
  },
  {
   "slug": "a421v-spatial-learning-working-memory-impaired",
   "role": "empirical",
   "panel": "fig2B, fig2C, fig2D",
   "plain": "Young adult Kcnc1-A421V mice are slower to learn the Barnes maze and alternate less in the Y-maze, but retain what they learned."
  },
  {
   "slug": "a421v-weight-reduced-milestones-normal",
   "role": "empirical",
   "panel": "fig1—figure supplement 2B, 2C, 2D, 2E",
   "plain": "Kcnc1-A421V mice weigh less and have smaller brains than littermates, yet reach the usual early developmental milestones on time."
  },
  {
   "slug": "alt-inhibitory-dysfunction-present-juvenile",
   "role": "hypothesis",
   "panel": "",
   "plain": "Inhibition in Kcnc1-A421V mice is already impaired in juveniles, so the deficit is fixed from the start rather than worsening with age."
  },
  {
   "slug": "excitatory-neurons-unaffected-adult",
   "role": "control",
   "panel": "fig5—figure supplement 1D, Table 2 (layer IV exc. cells)",
   "plain": "Excitatory neurons in adult Kcnc1-A421V mice fire like wild-type ones, apart from needing slightly less current to start firing."
  },
  {
   "slug": "excitatory-neurons-unaffected-juvenile",
   "role": "control",
   "panel": "fig5B, fig5C, fig5D, fig5E, fig5F, fig5G, fig5K, Table 1 (layer IV exc.)",
   "plain": "Excitatory neurons in juvenile Kcnc1-A421V mice show normal synaptic transmission and normal excitability."
  },
  {
   "slug": "hypothesis-a421v-causes-kv31-lof",
   "role": "hypothesis",
   "panel": "hypothesis",
   "plain": "The A421V variant weakens Kv3.1 by keeping the channel from reaching the cell surface, not by changing how the channels that arrive work."
  },
  {
   "slug": "hypothesis-pv-dysfunction-drives-encephalopathy",
   "role": "hypothesis",
   "panel": "hypothesis",
   "plain": "Losing Kv3.1 in parvalbumin interneurons is by itself enough to produce the seizures, sudden death and cognitive deficits of KCNC1 disease."
  },
  {
   "slug": "hypothesis-pv-in-selective-vulnerability",
   "role": "hypothesis",
   "panel": "hypothesis",
   "plain": "Kv3.1 loss impairs fast-spiking parvalbumin interneurons and spares excitatory neurons, hitting hardest where Kv3.2 cannot compensate."
  },
  {
   "slug": "in-vivo-hypersynchronous-discharges-mutant-only",
   "role": "empirical",
   "panel": "fig8B, fig8C, fig8D",
   "plain": "Awake Kcnc1-A421V mice show bursts of synchronised cortical activity accompanied by brief twitches, and wild-type mice never do."
  },
  {
   "slug": "in-vivo-pv-minus-transient-frequency-increased",
   "role": "empirical",
   "panel": "fig8G, fig8H, fig8I, fig8J",
   "plain": "During quiet rest, excitatory cells in Kcnc1-A421V mice are active more often while parvalbumin cells respond more weakly."
  },
  {
   "slug": "inhibitory-dysfunction-progresses-to-adulthood",
   "role": "synthesis",
   "panel": "figs 2-4",
   "plain": "Inhibitory transmission is normal in juvenile Kcnc1-A421V mice and impaired by young adulthood, so the deficit emerges with age."
  },
  {
   "slug": "kcnc1-wet-lab-primary-claims",
   "role": "methodological",
   "panel": "all figures (assessment)",
   "plain": "The paper's main phenotype claims rest on the knock-in mouse colony and bench recordings, and cannot be checked from deposited data alone."
  },
  {
   "slug": "layer-v-pv-ins-subtle-impairment",
   "role": "empirical",
   "panel": "fig4—figure supplement 2",
   "plain": "Layer V parvalbumin interneurons in juvenile mutants are only mildly impaired, firing less at the strongest current injections."
  },
  {
   "slug": "prediction-cognitive-deficits",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Kcnc1-A421V mice should be slower to learn the Barnes maze and show weaker Y-maze working memory, with no locomotor explanation."
  },
  {
   "slug": "prediction-excitatory-neurons-spared",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Excitatory neurons should be unaffected in Kcnc1-A421V mice at both juvenile and adult ages, since they barely rely on Kv3.1."
  },
  {
   "slug": "prediction-impairment-grades-with-kv31-dependence",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Deficits should be largest in parvalbumin cells that depend most on Kv3.1 and milder where Kv3.2 can take over."
  },
  {
   "slug": "prediction-kv31-surface-expression-reduced",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Mutant parvalbumin interneurons should hold less Kv3.1 at the membrane and more inside the cell, while the remaining channels open normally."
  },
  {
   "slug": "prediction-network-hyperexcitability-in-vivo",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Awake Kcnc1-A421V mice should show synchronised cortical discharges and more active excitatory cells during quiet rest."
  },
  {
   "slug": "prediction-progressive-synaptic-failure",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Inhibitory synapses made by parvalbumin interneurons should work normally in juveniles and release transmitter differently in young adults."
  },
  {
   "slug": "prediction-pv-in-firing-impaired",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Parvalbumin interneurons in mutants should fire more slowly with broader, less sharply repolarising spikes, already in juveniles."
  },
  {
   "slug": "prediction-pv-in-k-current-reduced",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Parvalbumin interneurons carrying one copy of the variant should lose voltage-gated potassium current, and lose more than half of it."
  },
  {
   "slug": "prediction-seizures-and-sudep",
   "role": "prediction",
   "panel": "prediction",
   "plain": "Kcnc1-A421V mice should have spontaneous convulsive seizures on video-EEG and die suddenly after tonic-clonic seizures."
  },
  {
   "slug": "pv-in-ap-waveform-altered-downstroke-apd50",
   "role": "empirical",
   "panel": "fig4E, fig4J, Table 1, Table 2",
   "plain": "Spikes in mutant parvalbumin interneurons repolarise more slowly and last longer, at both juvenile and adult ages."
  },
  {
   "slug": "pv-in-inhibitory-synapse-altered-adult",
   "role": "empirical",
   "panel": "fig7F, fig7G, fig7H, fig7I",
   "plain": "In adult mutants, inhibitory signals from parvalbumin interneurons onto excitatory cells are larger but weaken faster during repeated firing."
  },
  {
   "slug": "pv-in-inhibitory-synapse-intact-juvenile",
   "role": "empirical",
   "panel": "fig6F, fig6G, fig6H, fig6I, fig6J, fig6K, fig6L",
   "plain": "In juvenile mutants, inhibitory transmission from parvalbumin interneurons onto excitatory cells is no different from wild-type."
  },
  {
   "slug": "pv-ins-impaired-maximal-firing",
   "role": "empirical",
   "panel": "fig2, fig3",
   "plain": "Parvalbumin interneurons from Kcnc1-A421V mice cannot sustain the high firing rates that wild-type cells reach."
  },
  {
   "slug": "pv-ins-reduced-k-current-density",
   "role": "empirical",
   "panel": "fig2",
   "plain": "Parvalbumin interneurons in Kcnc1-A421V mice carry less voltage-gated potassium current than wild-type cells."
  },
  {
   "slug": "rtn-neurons-impaired-excitability",
   "role": "empirical",
   "panel": "fig4—figure supplement 3",
   "plain": "Parvalbumin neurons of the reticular thalamic nucleus in juvenile mutants fire fewer rebound spikes and repolarise more slowly."
  },
  {
   "slug": "scope-a421v-knockin-mouse",
   "role": "scope",
   "panel": "scope",
   "plain": "All claims come from one heterozygous Kcnc1-A421V knock-in mouse line, studied in somatosensory cortex and thalamus at set ages."
  },
  {
   "slug": "spontaneous-seizures-and-sudep-kcnc1",
   "role": "empirical",
   "panel": "fig9A, fig9B, fig9C",
   "plain": "Most Kcnc1-A421V mice have spontaneous convulsive seizures on video-EEG and some die suddenly after one, while wild-types have none."
  }
 ]
}