Intrinsic excitability increase in cerebellar Purkinje cells after delay eye-blink 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 journalArticle

5 Scopus citations

Abstract

Cerebellar-based learning is 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 downregulation of calcium-dependent SK-type K + channels, which contribute to a medium-slow afterhyperpolarization (AHP) after spike bursts, regulating membrane excitability. In the hippocampus, intrinsic plasticity plays a role in trace eye-blink conditioning; however, corresponding excitability changes in the cerebellum in associative learning, such as in trace or delay eye-blink conditioning, are less well studied. Whole-cell patch-clamp recordings were obtained from Purkinje cells in cerebellar slices prepared from male mice ~48 h after they learned a delay eye-blink conditioning task. Over a period of repeated training sessions, mice received either paired trials of a tone coterminating with a periorbital shock (conditioning) or trials in which these stimuli were randomly presented in an unpaired manner (pseudoconditioning). Purkinje cells from conditioned mice show a significantly reduced AHP after trains of parallel fiber stimuli and after climbing fiber evoked complex spikes. The number of spikelets in the complex spike waveform is increased after conditioning. 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 eye-blink conditioning, and point toward a downregulation of SK channels as a potential underlying mechanism. The observation that this learning effect lasts at least up to 2 d after training shows that intrinsic plasticity regulates excitability in the long term.

Original languageEnglish (US)
Pages (from-to)2038-2046
Number of pages9
JournalJournal of Neuroscience
Volume40
Issue number10
DOIs
StatePublished - Mar 4 2020

Keywords

  • Cerebellum
  • Engram
  • Learning
  • Memory
  • Neuron
  • Plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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