The Genetically Epilepsy Prone Rat (GEPR/3Hsd) exhibits profound myoclonus in response to an intense auditory stimulus. We carried out immunohistochemical and physiological experiments to determine the neurochemical state of the olivocerebellar system of GEPR/3Hsd rats. Alternate 40-μm sections were taken from the inferior olive (IO), deep cerebellar nuclei (DCN) and cerebellar cortex of GEPR/3Hsd and inbred nonseizing controls (GEPR/CHsd). Tissue from 4 matched pairs of GEPR/3Hsd and control brains were processed for immunocytochemical detection of serotonin (5-HT; antibodies obtained from IncStar). Quantitative optical densitometry revealed a 10% reduction in 5-HT immunoreactivity in both the principal subnucleus and lateral portion of the dorsal accessory subnucleus of the IO in GEPR/3Hsd rats (both p < 0.05). No alteration in 5-HT content was seen in other IO subnuclei, the DCN, or cerebellar cortex. Functional measures of IO activity revealed a marked insensitivity of the GEPR/3Hsd to the tremorogenic effects of harmaline as compared to controls. Harmaline's ability to produce tremor is known to be due to rhythmic activation of the IO and to be correlated with the concentration of olivary 5-HT. Our studies suggest that defects in 5-HT-mediated modulation of the IO may predispose the GEPR/3Hsd rat to myoclonus. Supported by the Myoclonus Research Foundation and NINDS NS-31224.
|Original language||English (US)|
|State||Published - 1996|
ASJC Scopus subject areas
- Molecular Biology