Cerebellar learning modulates surface expression of a voltage-gated ion channel in cerebellar cortex

- Eyeblink conditioning stimuli regulate cerebellar cell surface expression of Kv1.2.
- Three sessions of unpaired stimulus exposure reduced surface Kv1.2 at basket cell pinceaux.
- Three sessions of paired stimulus exposure had no effect on surface Kv1.2 expression.
- Half session of unpaired stimulus exposure increased surface Kv1.2 expression in Purkinje cells.
- Half session of paired stimulus exposure increased Kv1.2 expression only in rats not expressing CRs.

Numerous experiments using ex vivo electrophysiology suggest that mammalian learning and memory involves regulation of voltage-gated ion channels in terms of changes in function. Yet, little is known about learning-related regulation of voltage-gated ion channels in terms of changes in expression. In two experiments, we examined changes in cell surface expression of the voltage-gated potassium channel alpha-subunit Kv1.2 in a discrete region of cerebellar cortex after eyeblink conditioning (EBC), a well-studied form of cerebellar-dependent learning. Kv1.2 in cerebellar cortex is expressed almost entirely in basket cells, primarily in the axon terminal pinceaux (PCX) region, and Purkinje cells, primarily in dendrites. Cell surface expression of Kv1.2 was measured using both multiphoton microscopy, which allowed measurement confined to the PCX region, and biotinylation/western blot, which measured total cell surface expression. In the first experiment, rats underwent three sessions of EBC, explicitly unpaired stimulus exposure, or context-only exposure and the results revealed a decrease in Kv1.2 cell surface expression in the unpaired group as measured with microscopy but no change as measured with western blot. In the second experiment, the same three training groups underwent only one half of a session of training, and the results revealed an increase in Kv1.2 cell surface expression in the unpaired group as measured with western blot but no change as measured with microscopy. In addition, rats in the EBC group that did not express conditioned responses (CRs) exhibited the same increase in Kv1.2 cell surface expression as the unpaired group. The overall pattern of results suggests that cell surface expression of Kv1.2 is changed with exposure to EBC stimuli in the absence, or prior to the emergence, of CRs.