Cerebellar secretin modulates eyeblink classical conditioning.
We have previously shown that intracerebellar infusion of the neuropeptide secretin enhances the acquisition phase of eyeblink conditioning (EBC). Here, we sought to test whether endogenous secretin also regulates EBC and to test whether the effect of exogenous and endogenous secretin is specific to acquisition. In Experiment 1, rats received intracerebellar infusions of the secretin receptor antagonist 5-27 secretin or vehicle into the lobulus simplex of cerebellar cortex immediately prior to sessions 1-3 of acquisition. Antagonist-infused rats showed a reduction in the percentage of eyeblink CRs compared with vehicle-infused rats. In Experiment 2, rats received intracerebellar infusions of secretin or vehicle immediately prior to sessions 1-2 of extinction. Secretin did not significantly affect extinction performance. In Experiment 3, rats received intracerebellar infusions of 5-27 secretin or vehicle immediately prior to sessions 1-2 of extinction. The secretin antagonist did not significantly affect extinction performance. Together, our current and previous results indicate that both exogenous and endogenous cerebellar secretin modulate acquisition, but not extinction, of EBC. We have previously shown that (1) secretin reduces surface expression of the voltage-gated potassium channel α-subunit Kv1.2 in cerebellar cortex and (2) intracerebellar infusions of a Kv1.2 blocker enhance EBC acquisition, much like secretin. Kv1.2 is almost exclusively expressed in cerebellar cortex at basket cell-Purkinje cell pinceaus and Purkinje cell dendrites; we propose that EBC-induced secretin release from PCs modulates EBC acquisition by reducing surface expression of Kv1.2 at one or both of these sites.
Department of Psychology, University of Vermont, Burlington, Vermont 05405, USA.
Jason R
JR
Fuchs
Department of Psychology, University of Vermont, Burlington, Vermont 05405, USA.
Gain M
GM
Robinson
Department of Psychology, University of Vermont, Burlington, Vermont 05405, USA.
Aaron M
AM
Dean
Department of Psychology, University of Vermont, Burlington, Vermont 05405, USA.
Heidi E
HE
Schoenberg
Department of Pharmacology, University of Vermont, Burlington, Vermont 05405, USA.
Michael R
MR
Williams
Department of Pharmacology, University of Vermont, Burlington, Vermont 05405, USA.
Anthony D
AD
Morielli
Department of Psychology, University of Vermont, Burlington, Vermont 05405, USA john.green@uvm.edu.
John T
JT
Green
D000818:Animals; D002408:Catheters, Indwelling; D002525:Cerebellar Cortex / Q000187:drug effects / Q000502:physiology*; D003215:Conditioning, Eyelid / Q000187:drug effects / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D051663:Kv1.2 Potassium Channel / Q000378:metabolism; D008297:Male; D011689:Purkinje Cells / Q000378:metabolism; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012633:Secretin / Q000378:metabolism*
D051663:Kv1.2 Potassium Channel; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin