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

• Main Authors: Giorgio Grasselli, Henk-Jan Boele, Heather K Titley, Nora Bradford, Lisa van Beers, Lindsey Jay, Gerco C Beekhof, Silas E Busch, Chris I De Zeeuw, Martijn Schonewille, Christian Hansel
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2020-01-01
• Series: PLoS Biology
• Online Access: https://doi.org/10.1371/journal.pbio.3000596
• ISSN: 1544-9173; 1545-7885

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.