SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning-specific memory traces

PLoS Biol. 2020 Jan 6;18(1):e3000596. doi: 10.1371/journal.pbio.3000596. eCollection 2020 Jan.

Abstract

Neurons store information by changing synaptic input weights. In addition, they can adjust their membrane excitability to alter spike output. Here, we demonstrate a role of such "intrinsic plasticity" in behavioral learning in a mouse model that allows us to detect specific consequences of absent excitability modulation. Mice with a Purkinje-cell-specific knockout (KO) of the calcium-activated K+ channel SK2 (L7-SK2) show intact vestibulo-ocular reflex (VOR) gain adaptation but impaired eyeblink conditioning (EBC), which relies on the ability to establish associations between stimuli, with the eyelid closure itself depending on a transient suppression of spike firing. In these mice, the intrinsic plasticity of Purkinje cells is prevented without affecting long-term depression or potentiation at their parallel fiber (PF) input. In contrast to the typical spike pattern of EBC-supporting zebrin-negative Purkinje cells, L7-SK2 neurons show reduced background spiking but enhanced excitability. Thus, SK2 plasticity and excitability modulation are essential for specific forms of motor learning.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / genetics*
  • Animals
  • Cerebellum / cytology
  • Cerebellum / metabolism
  • Female
  • Learning / physiology*
  • Male
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / physiology*
  • Neuronal Plasticity / physiology
  • Purkinje Cells / metabolism*
  • Reflex, Vestibulo-Ocular
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism
  • Small-Conductance Calcium-Activated Potassium Channels / physiology*

Substances

  • Kcnn2 protein, mouse
  • Small-Conductance Calcium-Activated Potassium Channels

Associated data

  • Dryad/10.5061/dryad.mh4f7n3