Article

c-Fos immunohistochemical mapping of the audiogenic seizure network and tonotopic neuronal hyperexcitability in the inferior colliculus of the Frings mouse.

Department of Pharmacology and Toxicology, 20 S 2030 E Rm 408, Salt Lake City, UT 84112, USA.
Epilepsy Research (Impact Factor: 2.19). 12/2004; 62(1):13-25. DOI: 10.1016/j.eplepsyres.2004.06.007
Source: PubMed

ABSTRACT The Frings mouse is a model of audiogenic seizure (AGS) susceptibility. The genetic locus responsible for the AGS phenotype in the Frings mouse has been named monogenic audiogenic seizure-susceptible (MASS1). MASS1 is unique in that it is one of only two identified seizure loci that are not associated with an ion channel mutation. Furthermore, Frings mice display a robust AGS phenotype demonstrating very high and prolonged susceptibility to sound-induced tonic extension seizures. The purpose of this investigation was to use c-Fos immunohistochemistry to map the brain structures involved in the Frings AGS and to examine neuronal hyperexcitability in the inferior colliculus, the brain structure that is recognized as the site of AGS initiation. AGS mapping revealed that intense seizure-induced neuronal activation was mostly limited to structures involved in a brainstem seizure network, including the external and dorsal nuclei of the inferior colliculus, as observed in other AGS rodents. Acoustically induced c-Fos expression in the central nucleus of the inferior colliculus to sub-AGS threshold tone stimulations displayed a greater level of neuronal activation in AGS-susceptible Frings, DBA/2J and noise-primed C57BL/6J mice compared to AGS-resistant C57BL/6J and CF1 mice. The AGS-susceptible mice also displayed c-Fos immunoreactivity that was more focused within the tonotopic response domain of the inferior colliculus compared to AGS-resistant mice. Furthermore, Frings mice displayed significantly greater tonotopic hyper-responsiveness compared to other AGS-susceptible mice.

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    • " and a faster decay of their inhibitory postsynaptic po - tentials ( IPSP ) in dentate gyrus ( Spigelman et al . , 2002 ) , sug - gesting that GABA tonic inhibition is critical towards the prevention of seizures . The reduction of GABR - d and GABR - a6 subunits in the IC may be related to hyperactivity in the IC when responding to sound stimuli ( Klein et al . , 2004 ; Kwon and Pierson , 1997 ) . Our study found that early age hearing loss di - minishes the expression of GABR - d and GABR - a6 subunits , thus promoting hyperactivity in the IC and ultimately inducing AGS at a later age ."
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    • "Expression of messenger cfos is a plausible mechanism for inducing abnormal neural plasticity by directing protein synthesis in the nucleus. Immunoreactivity for the immediate-early gene product, cFos, has also been examined in several animal seizure models in order to reveal brain regions recruited as a result of seizure activity (Fabene et al., 2004; Klein et al., 2004; Simler et al., 1999), and is thought to reflect non-specifically heightened neuronal excitability in these regions (Zhang et al., 2002). For example, cFos is upregulated in the dentate gyrus of EL mice following vestibular stimulation (tossing-up) and/or seizures (Nakagawa et al., 1999). "
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