Pavlovian eyeblink conditioning is severely impaired in tottering mice

J Neurophysiol. 2021 Feb 1;125(2):398-407. doi: 10.1152/jn.00578.2020. Epub 2020 Dec 16.

Abstract

Cacna1a encodes the pore-forming α1A subunit of CaV2.1 voltage-dependent calcium channels, which regulate neuronal excitability and synaptic transmission. Purkinje cells in the cortex of cerebellum abundantly express these CaV2.1 channels. Here, we show that homozygous tottering (tg) mice, which carry a loss-of-function Cacna1a mutation, exhibit severely impaired learning in Pavlovian eyeblink conditioning, which is a cerebellar-dependent learning task. Performance of reflexive eyeblinks is unaffected in tg mice. Transient seizure activity in tg mice further corrupted the amplitude of eyeblink conditioned responses. Our results indicate that normal calcium homeostasis is imperative for cerebellar learning and that the oscillatory state of the brain can affect the expression thereof.NEW & NOTEWORTHY In this study, we confirm the importance of normal calcium homeostasis in neurons for learning and memory formation. In a mouse model with a mutation in an essential calcium channel that is abundantly expressed in the cerebellum, we found severely impaired learning in eyeblink conditioning. Eyeblink conditioning is a cerebellar-dependent learning task. During brief periods of brain-wide oscillatory activity, as a result of the mutation, the expression of conditioned eyeblinks was even further disrupted.

Keywords: CaV2.1 VDCC; cerebellar learning; eyeblink conditioning; tottering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blinking*
  • Calcium / metabolism
  • Calcium Channels, N-Type / genetics*
  • Cerebellum / physiology
  • Conditioning, Classical*
  • Female
  • Homozygote
  • Male
  • Mice
  • Mice, Inbred C57BL

Substances

  • Calcium Channels, N-Type
  • voltage-dependent calcium channel (P-Q type)
  • Calcium