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

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 consequences of absent excitability modulation, without alterations in synaptic plasticity. SK2-type, calcium-dependent K+ conductances are involved in excitability control as they contribute to the afterhyperpolarization (AHP) following spike bursts. SK2 channels are downregulated in activity-dependent intrinsic plasticity in cerebellar Purkinje cells. To study the relevance of excitability adjustment in cerebellar learning, we generated and tested mice with a Purkinje cell-specific SK2 knockout (L7-SK2). Deletion of SK2 channels enhanced Purkinje cell excitability and selectively prevented intrinsic plasticity. L7-SK2 mice showed impairment of eyeblink conditioning, but intact vestibulo-ocular reflex gain adaptation. Thus, ...