title: Morphofunctional alterations in the olivocochlear efferent system of the genetic audiogenic seizure-prone hamster GASH:Sal.
abstract: The genetic audiogenic seizure hamster (GASH:Sal) is a model of a form of reflex epilepsy that is manifested as generalized tonic-clonic seizures induced by external acoustic stimulation. The morphofunctional alterations in the auditory system of the GASH:Sal that may contribute to seizure susceptibility have not been thoroughly determined. In this study, we analyzed the olivocochlear efferent system of the GASH:Sal from the organ of Corti, including outer and inner hair cells, to the olivocochlear neurons, including shell, lateral, and medial olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To achieve this, we carried out a multi-technical approach that combined auditory hearing screenings, scanning electron microscopy, morphometric analysis of labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results showed that the GASH:Sal exhibited higher auditory brain response (ABR) thresholds than their controls, as well as absence of distortion-product of otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE results also showed differences between the left and right ears, indicating asymmetrical hearing alterations in the GASH:Sal. These alterations in the peripheral auditory activity correlated with morphological alterations. At the cochlear level, the scanning electron microscopy analysis showed marked distortions of the stereocilia from basal to apical cochlear turns in the GASH:Sal, which were not observed in the control hamsters. At the brainstem level, MOC, LOC, and shell neurons had reduced soma areas compared with control animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated that the morphofunctional alterations of the olivocochlear efferent system are innate components of the GASH:Sal, which might contribute to their susceptibility to audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
authors: Institute of Neuroscience of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain; Department of Cell Biology and Pathology, Faculty of Medicine, University of Salamanca, Salamanca, Spain.
authors: David
authors: D
authors: Sánchez-Benito
authors: Institute of Neuroscience of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain; Department of Cell Biology and Pathology, Faculty of Medicine, University of Salamanca, Salamanca, Spain.
authors: Ricardo
authors: R
authors: Gómez-Nieto
authors: Institute of Neuroscience of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors: Sonia
authors: S
authors: Hernández-Noriega
authors: Laboratory of Neurobiology of Hearing, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors: Adriana Andrade Batista
authors: AAB
authors: Murashima
authors: Neurophysiology and Experimental Neuroethology Laboratory, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors: José Antonio Cortes
authors: JAC
authors: de Oliveira
authors: Neurophysiology and Experimental Neuroethology Laboratory, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors: Norberto
authors: N
authors: Garcia-Cairasco
authors: Institute of Neuroscience of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain; Department of Cell Biology and Pathology, Faculty of Medicine, University of Salamanca, Salamanca, Spain. Electronic address: lopezde@usal.es.
authors: Dolores E
authors: DE
authors: López
authors: Laboratory of Neurobiology of Hearing, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
authors: Miguel Angelo
authors: MA
authors: Hyppolito
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects*; D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D001933:Brain Stem / Q000473:pathology / Q000648:ultrastructure; D003051:Cochlea / Q000473:pathology* / Q000648:ultrastructure; D006224:Cricetinae; D004195:Disease Models, Animal; D020195:Epilepsy, Reflex / Q000235:genetics / Q000473:pathology*; D008647:Mesocricetus; D009847:Olivary Nucleus / Q000473:pathology* / Q000648:ultrastructure; D017084:Otoacoustic Emissions, Spontaneous / Q000235:genetics; D012640:Seizures / Q000235:genetics / Q000473:pathology*
keywords: Animal models of epilepsy; Distortion-product otoacoustic emission (DPOAE); Hair cell; Olivocochlear neurons; Pathogenesis of epilepsy; Reflex seizures; Scanning electron microscopy