Fuchs, J. R., Robinson, G. R., & Green, J. T.
Eyeblink conditioning (EBC) is a well-studied form of classical conditioning supported by plasticity in the cerebellum. EBC involves trials in which a tone conditioned stimulus (CS) precedes an eyelid stimulation unconditioned stimulus (US). The conditioned response (CR) is an eyeblink to the CS. Both Purkinje cells (PCs) in cerebellar cortex and interpositus nucleus (IPN) neurons receive CS and US inputs. PCs normally inhibit the IPN but lift this inhibition during EBC. PCs are powerfully regulated by basket cells (BC), a cerebellar inhibitory interneuron whose axon terminals have the highest concentration in the brain of the voltage-gated K+ channel α-subunit, Kv1.2. Previous research shows that PCs express and release secretin, surface Kv1.2 in BC terminals is reduced by secretin and secretin increases IPSCs in PCs, which is blocked by GABAA antagonists.
We have shown that infusing either a Kv1.2 blocker or secretin into lobulus simplex in cerebellar cortex facilitates conditioning presumably by increasing inhibition of PCs, thereby reducing inhibition of IPN neurons. The current experiments expand on these findings. In Experiment 1, rats received infusions of the secretin receptor antagonist, 5-27 secretin, or vehicle into lobulus simplex immediately prior to Sessions 1-3 of EBC. Rats that received 5-27 secretin showed slower acquisition. In Experiment 2, rats received infusions of secretin or vehicle into lobulus simplex immediately prior to Sessions 1 or 2 of extinction. Rats that received secretin prior to Session 1 of extinction showed slower extinction. In Experiment 3, rats received infusions of 5-27 secretin or vehicle into lobulus simplex prior to Sessions 1 or 2 of extinction.
We predict that rats that receive 5-27 secretin prior to Session 1 of extinction will extinguish faster. Our working model is that cerebellar cortical secretin modulates EBC by reducing surface levels of Kv1.2 at BC terminals, thereby increasing inhibition of PCs.