Intrinsic Excitability Increase in Cerebellar Purkinje Cells Following Delay Eyeblink Conditioning in Mice

Heather K. Titley, Gabrielle V. Watkins, Carmen Lin, Craig Weiss, Michael McCarthy, John F. Disterhoft, Christian Hansel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Cerebellar learning is canonically thought to rely on synaptic plasticity, particularly at synaptic inputs to Purkinje cells. Recently, however, other complementary mechanisms have been identified. Intrinsic plasticity is one such mechanism, and depends in part on the down-regulation of calcium-dependent SK-type K channels, which is associated with an increase in neuronal excitability. In the hippocampus, SK-mediated intrinsic plasticity has been shown to play a role in trace eyeblink conditioning; however, it is not yet known how intrinsic plasticity contributes to a cerebellar learning task such as delay eyeblink conditioning. Whole cell recordings were obtained from acute cerebellar slices from mice ~48 hours after learning a delay eyeblink conditioning task. Over a period of repeated training sessions mice received either distinctly paired trials of a tone co-terminating with a periorbital shock (conditioned mice) or trials in which these stimuli were presented in an unpaired manner (pseudoconditioned mice). Conditioned mice show a significantly reduced afterhyperpolarization (AHP) following trains of parallel fiber stimuli. Moreover, we find that SK-dependent intrinsic plasticity is occluded in conditioned, but not pseudoconditioned mice. These findings show that excitability is enhanced in Purkinje cells after delay eyeblink conditioning and point toward a downregulation of SK channels as a potential underlying mechanism.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Apr 23 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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