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


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.

SUBMITTER: Grasselli G 

PROVIDER: S-EPMC6964916 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Grasselli Giorgio G   Boele Henk-Jan HJ   Titley Heather K HK   Bradford Nora N   van Beers Lisa L   Jay Lindsey L   Beekhof Gerco C GC   Busch Silas E SE   De Zeeuw Chris I CI   Schonewille Martijn M   Hansel Christian C  

PLoS biology 20200106 1


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  ...[more]

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