Cerebellar cortical inhibition and classical eyeblink conditioning.
The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning/memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a gamma-aminobutyric acid type A receptor (GABA(A)R) agonist and a noncompetitive GABA(A)R antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABA(A)Rs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.
Bao
Shaowen
S
Neuroscience Program, University of Southern California, Los Angeles, CA 90089-2520, USA.
Chen
Lu
L
Kim
Jeansok J
JJ
Thompson
Richard F
RF
D000200:Action Potentials; D000818:Animals; D001767:Blinking / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D011963:Receptors, GABA-A / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D005680:gamma-Aminobutyric Acid