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        <title>The role of the inferior colliculus in a genetic model of audiogenic seizures</title>
        <author>Ribak</author>
        <author>Morin</author>
      </titleStmt>
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        <bibl>
          <title>The role of the inferior colliculus in a genetic model of audiogenic seizures</title>
          <date>1995</date>
          <publisher>Anatomy and Embryology</publisher>
          <idno type="DOI">10.1007/bf00534681</idno>
          
          <idno type="record">ribak1995-the-role-of-the-inferior-colliculu</idno>
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          <note type="rights">open-access</note>
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        <person xml:id="paper"><p>the paper's own words</p></person>
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      <span xml:id="t0" type="claim_type" ana="#claim_type" resp="#paper">
        <label>mechanism</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t1" type="phenomenon" ana="#phenomenon" resp="#paper">
        <label>audiogenic seizures</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t2" type="method" ana="#method" resp="#paper">
        <label>review</label>
        <term>review</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t3" type="mechanisms" ana="#mechanisms[0]" resp="#tagger">
        <label>mechanisms</label>
        <term>GABA is taken back up more efficiently in the ICCN of GEPR-9s, so less GABA remains in the synapse to reach postsynaptic GABA receptors, inhibition is weakened, and seizures start in that nucleus despite the extra GABAergic neurons.</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t4" type="mechanisms" ana="#mechanisms[1]" resp="#tagger">
        <label>mechanisms</label>
        <term>Alternatively, excitation is enhanced in the ICCN through overexpression of glutamate receptors, which would fit the raised glutamate and aspartate levels measured there.</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t5" type="mechanisms" ana="#mechanisms[2]" resp="#tagger">
        <label>mechanisms</label>
        <term>Seizure activity initiated in the ICCN is carried out of the colliculus along the bilateral ICCN-to-external-nucleus projection and onward to the superior colliculus and pontine reticular formation.</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t6" type="limitations" ana="#limitations[0]" resp="#tagger">
        <label>How the surplus of small GABAergic neurons produces the observed pharmacological defects at GABAergic synapses is unresolved.</label>
        <note>what this limits: the causal link between the cell-count finding and the pharmacology: IT REMAINS TO BE RESOLVED HOW THE INCREASE IN SMALL GABAergic NEURONS IN THE ICCN IS RESPONSIBLE FOR THE KNOWN PHARMACOLOGICAL DEFECTS OBSERVED AT GABAergic SYNAPSES</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t7" type="limitations" ana="#limitations[1]" resp="#tagger">
        <label>The contribution of other brainstem structures to seizure propagation has not been established.</label>
        <note>what this limits: the seizure-propagation account: FURTHER STUDIES ARE REQUIRED TO DETERMINE THE RELATIONSHIP OF THESE OTHER STRUCTURES TO THE PROPAGATION OF SEIZURE ACTIVITY</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t8" type="limitations" ana="#limitations[2]" resp="#tagger">
        <label>The two candidate mechanisms offered for seizure initiation remain untested.</label>
        <note>what this limits: the initiation mechanism: TWO HYPOTHESES WILL BE TESTED IN FUTURE STUDIES: (1) INCREASED GABA UPTAKE, AND (2) INCREASED GLUTAMATE RECEPTOR EXPRESSION</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t9" type="limitations" ana="#limitations[3]" resp="#tagger" cert="1.0">
        <label>The animal strains are named by their assigned score on a 0-9 behavioural rating scale.</label>
        <note>what this limits: any comparison between GEPR strains: a strain displaying moderate seizures with an assigned seizure score of 3 is designated GEPR-3 and used as an animal model, so the strain name is a position on the rating scale</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t10" type="limitations" ana="#limitations[4]" resp="#tagger" cert="1.0">
        <label>The rating scale&#x27;s levels are defined by observed behaviour, and the paper prints them.</label>
        <note>what this limits: any seizure score quoted from this literature: the seizures are scored on a 0-9 scale with 0 being no seizure and 9 a fit of wild running with an accompanying tonic seizure</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <span xml:id="t11" type="limitations" ana="#limitations[5]" resp="#tagger" cert="1.0">
        <label>The cell-type census of the region is stated as a suggestion from these results.</label>
        <note>what this limits: the claim that four of six ICCN cell types are GABAergic: the authors give it as what these results suggest</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t12" type="concepts" ana="#concepts[0]" resp="#paper">
        <label>GEPR-3</label>
        <term>GEPR-3</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t13" type="concepts" ana="#concepts[1]" resp="#paper">
        <label>seizure score</label>
        <term>seizure score</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t14" type="concepts" ana="#concepts[2]" resp="#paper">
        <label>animal model</label>
        <term>animal model</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t15" type="concepts" ana="#concepts[3]" resp="#paper">
        <label>Genetically epilepsy-prone rats</label>
        <term>Genetically epilepsy-prone rats</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t16" type="concepts" ana="#concepts[4]" resp="#paper">
        <label>GABAergic inhibitory neurons</label>
        <term>GABAergic inhibitory neurons</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t17" type="senses" ana="#senses[0]" resp="#tagger" cert="1.0">
        <label>GEPR-3 - A STRAIN NAME THAT IS A SCALE SCORE: a rat strain showing moderate seizures is assigned a seizure score of 3 and thereby designated GEPR-3, so a behavioural rating becomes a strain name and then a fixed kind of animal; a later comparison of GEPR-3 with GEPR-9 compares two points on an ordinal scale that have been reified into two categories</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t18" type="senses" ana="#senses[1]" resp="#tagger" cert="1.0">
        <label>the seizure score - A 0-9 ORDINAL WITH BEHAVIOURAL ENDPOINTS: 0 is no seizure and 9 is one fit of wild running with an accompanying tonic seizure, so the scale is anchored in observable behaviour and the number that travels in a strain name is a rank on it</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t19" type="senses" ana="#senses[2]" resp="#tagger" cert="1.0">
        <label>the ICCN cell-type count - OFFERED AS A SUGGESTION: the authors write that these results SUGGEST four of the six major cell types are GABAergic inhibitory neurons, so the census is a reading of the data rather than an enumeration</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t20" type="claim_relations" ana="#claim_relations[0]" resp="#tagger">
        <label>builds-on → Faingold et al. (1986a) hypothesis that GABA uptake is more efficient in the ICCN of GEPR-9s</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t21" type="claim_relations" ana="#claim_relations[1]" resp="#tagger">
        <label>contradicts → the disinhibition account carried over from hippocampal dentate gyrus findings (Farias et al. 1992; Buckmaster and Schwartzkroin 1994)</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t22" type="claim_relations" ana="#claim_relations[2]" resp="#tagger">
        <label>builds-on → Faye-Lund and Osen&#x27;s (1985) description of the rat inferior colliculus</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t23" type="concept_edges" ana="#concept_edges[0]" resp="#tagger">
        <label>GEPR-3 —is-a→ animal model</label>
        <term>GEPR-3</term>
        <term>animal model</term>
        <note>differs in: what fixes the category: an assigned score of 3 on the 0-9 seizure scale · strength of the relation: 1</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t24" type="content_tags" ana="#content_tags.statistics[0]" resp="#tagger">
        <label>correlation</label>
        <term>correlation</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t25" type="content_tags" ana="#content_tags.statistics[1]" resp="#tagger">
        <label>correlation</label>
        <term>correlation</term>
        <note>WHOSE RESULT THIS IS: ns in the ICCN and the audiogenic response score (Ribak et al. 1988b). - THE RESULT OR THE NUMBER IS THE CITED WORK&#x27;S. Read, not swept - the trailing-citation shape is about 55% precise and the main clause is what decides it. Second reading pass over the 25 candidates left after 2026-08-25 11:39: 9 marked, 16 refused. the same sentence, tagged twice.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t26" type="content_tags" ana="#content_tags.statistics[2]" resp="#tagger">
        <label>significance test</label>
        <term>significance test</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t27" type="content_tags" ana="#content_tags.statistics[3]" resp="#tagger">
        <label>mean</label>
        <term>mean</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t28" type="content_tags" ana="#content_tags.statistics[4]" resp="#tagger">
        <label>cell counting (stereological-style counts per section)</label>
        <term>cell counting (stereological-style counts per section)</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t29" type="content_tags" ana="#content_tags.findings[0]" resp="#tagger">
        <label>Epilepsy-prone GEPR-9 rats have far more GAD-positive neurons in the inferior colliculus than Sprague-Dawley rats.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t30" type="content_tags" ana="#content_tags.findings[1]" resp="#tagger">
        <label>Two independent anatomical methods, immunocytochemistry and in situ hybridisation, were used to count GABAergic neurons.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t31" type="content_tags" ana="#content_tags.findings[2]" resp="#tagger">
        <label>Nissl analysis indicated the increase was not due to non-GABAergic neurons switching to a GABAergic phenotype.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t32" type="content_tags" ana="#content_tags.findings[3]" resp="#tagger">
        <label>Across GEPR-9s, Sprague-Dawley rats and their crossed offspring, the number of small neurons in the ICCN rises together with the audiogenic response score.</label>
        <note>WHOSE RESULT THIS IS: ns in the ICCN and the audiogenic response score (Ribak et al. 1988b). - THE RESULT OR THE NUMBER IS THE CITED WORK&#x27;S. Read, not swept - the trailing-citation shape is about 55% precise and the main clause is what decides it. Second reading pass over the 25 candidates left after 2026-08-25 11:39: 9 marked, 16 refused. &#x27;a significant positive…&#x27; - a self-citation to earlier work, which is still not THIS paper&#x27;s result.</note>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t33" type="content_tags" ana="#content_tags.findings[4]" resp="#tagger">
        <label>Moderately seizing GEPR-3 rats have significantly more small ICCN neurons than Sprague-Dawley rats, and the count matches the value the correlation line predicted in advance.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t34" type="content_tags" ana="#content_tags.findings[5]" resp="#tagger">
        <label>Knife cuts placed between the central and external nuclei of the IC block audiogenic seizures, as do lesions of the ICCN itself or of the lateral lemniscus.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t35" type="content_tags" ana="#content_tags.findings[6]" resp="#tagger">
        <label>The ICCN-to-external-nucleus projection is the route by which seizure activity leaves its site of initiation in the ICCN and propagates.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t36" type="content_tags" ana="#content_tags.findings[7]" resp="#tagger">
        <label>The number of axosomatic synapses per soma in the ICCN is the same in GEPR-9s and Sprague-Dawley rats, which rules out the idea that the extra GABAergic neurons act by adding inhibitory contacts onto cell bodies.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t37" type="content_tags" ana="#content_tags.findings[8]" resp="#tagger">
        <label>Audiogenic-seizure susceptibility in GEPRs was indicated to be an autosomal dominant trait.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t38" type="content_tags" ana="#content_tags.findings[9]" resp="#tagger">
        <label>Electron microscopy indicates that four of the six major cell types of the central nucleus of the inferior colliculus are GABAergic inhibitory neurons.</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t39" type="content_tags" ana="#content_tags.definitions[0]" resp="#tagger">
        <label>inferior colliculus (IC)</label>
        <term>inferior colliculus (IC)</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t40" type="content_tags" ana="#content_tags.definitions[1]" resp="#tagger">
        <label>three subdivisions of the IC</label>
        <term>three subdivisions of the IC</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t41" type="content_tags" ana="#content_tags.definitions[3]" resp="#tagger">
        <label>GEPR-3</label>
        <term>GEPR-3</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t42" type="content_tags" ana="#content_tags.definitions[4]" resp="#tagger">
        <label>genetically epilepsy-prone rats</label>
        <term>genetically epilepsy-prone rats</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t43" type="content_tags" ana="#content_tags.definitions[5]" resp="#tagger">
        <label>seizure score</label>
        <term>seizure score</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t44" type="content_tags" ana="#content_tags.variables[0]" resp="#tagger">
        <label>lesion site</label>
        <term>lesion site</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t45" type="content_tags" ana="#content_tags.variables[1]" resp="#tagger">
        <label>seizure severity</label>
        <term>seizure severity</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t46" type="content_tags" ana="#content_tags.variables[5]" resp="#tagger">
        <label>total number of Nissl-stained cells</label>
        <term>total number of Nissl-stained cells</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t47" type="content_tags" ana="#content_tags.variables[6]" resp="#tagger">
        <label>sizes of ICCN neurons</label>
        <term>sizes of ICCN neurons</term>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t48" type="content_tags" ana="#content_tags.quantities[0]" resp="#tagger">
        <label>200% — increase in small GAD-positive cells in the IC of GEPR-9s relative to Sprague-Dawley rats (medium cells increased 90%)</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t49" type="content_tags" ana="#content_tags.quantities[1]" resp="#tagger">
        <label>100% — increase in small Nissl-stained neurons in the ICCN of GEPRs, against a 30% increase for medium-sized neurons</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t50" type="content_tags" ana="#content_tags.quantities[2]" resp="#tagger">
        <label>70% — excess of small ICCN neurons in GEPR-9s over SD rats in the 2-micrometre semi-thin section counts, with medium neurons up 30%</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t51" type="content_tags" ana="#content_tags.quantities[3]" resp="#tagger">
        <label>25% ... 36% — proportion of small ICCN neurons that are GAD-positive in Sprague-Dawley rats versus GEPR-9s</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t52" type="content_tags" ana="#content_tags.quantities[4]" resp="#tagger">
        <label>0.91 — coefficient of linear correlation between audiogenic response score and the number of small ICCN neurons</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t53" type="content_tags" ana="#content_tags.quantities[5]" resp="#tagger">
        <label>29.50+2.17 — mean small-neuron count per unit area in the ICCN of GEPR-3 rats</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t54" type="content_tags" ana="#content_tags.quantities[6]" resp="#tagger">
        <label>3:1 — minimum ratio of seizure-prone to seizure-resistant offspring in GEPR-9 x Sprague-Dawley crosses</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
      </span>
      <span xml:id="t55" type="content_tags" ana="#content_tags.quantities[7]" resp="#tagger">
        <label>28 rats — number of animals contributing to the correlation between small-neuron number and audiogenic response score</label>
        <note type="quotation-withheld">Quotation withheld because this record is not cleared for redistribution.</note>
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      <p><note type="rights">The full text of this article is not redistributable, so it is
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      grounding status remain. The article itself is at https://doi.org/10.1007/bf00534681.</note></p>
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