Three decades of electrophysiological research on
cerebellar cortical activity underlying Pavlovian conditioning
have expanded our understanding of motor
learning in the brain. Purkinje cell simple spike suppression
is considered to be crucial in the expression
of conditional blink responses (CRs). However, trialby-
trial quantification of this link in awake behaving
animals is lacking, and current hypotheses regarding
the underlying plasticity mechanisms have diverged
from the classical parallel fiber one to the Purkinje
cell synapse LTD hypothesis. Here, we establish
that acquired simple spike suppression, acquired
conditioned stimulus (CS)-related complex spike
responses, and molecular layer interneuron (MLI)
activity predict the expression of CRs on a trial-bytrial
basis using awake behaving mice. Additionally,
we show that two independent transgenic mouse
mutants with impaired MLI function exhibit motor
learning deficits. Our findings suggest multiple
cerebellar cortical plasticity mechanisms underlying
simple spike suppression, and they implicate the
broader involvement of the olivocerebellar module
within the interstimulus interval.