Increased intrinsic membrane excitability is associated with hypertrophic olivary degeneration in spinocerebellar ataxia type 1.

Little is known about the factors that make inferior olive (IO) neurons susceptible to degeneration in the spinocerebellar ataxias (SCAs), a group of inherited neurodegenerative movement disorders. Another well-described form of IO degeneration, known as hypertrophic olivary degeneration (HOD), results from inhibitory denervation of the IO after brainstem injury. Here, we describe a novel finding of HOD in SCA1 without inhibitory denervation, in association with increased intrinsic membrane excitability and reduced potassium channel transcripts. This suggests that increased membrane excitability may be the underlying primary mechanism of HOD. Identifying hyperexcitability as the mechanistic driver of HOD would imply that reducing intrinsic IO excitability could be an effective strategy for treating diverse causes of both inherited and sporadic olivary degeneration.