Project Summary/Abstract
During motor learning, the cerebellum encodes memories of sensorimotor associations that predict deviant
action and, during recall of these associations, it will impose adaptive changes to instill corrective behavior. This
memory process depends on plasticity that alters the output of the cerebellum through learned patterns of
Purkinje cell spike output. Molecular layer interneurons (MLIs) are excited by parallel fibers that convey
sensorimotor information relayed through the mossy fiber pathway and, in turn, exert feedforward inhibition onto
postsynaptic Purkinje cells to reduce their spike output. MLI synapses are plastic and therefore may be
susceptible to learning-induced modification that would alter their inhibitory influence on Purkinje cells and, in
this way, impart adaptive behavior. Yet, a basic understanding of how MLIs are affected by experience and if
their activity is necessary for the expression of learning is unknown, creating a knowledge gap in the
understanding of cerebellar function. Therefore, the objective of this study is to elucidate the role of MLIs in
adaptive motor control in behaving mice and measure for learning-induced plasticity in their response properties.
This will be accomplished in two aims. In the first, we will use electrophysiology and genetically encoded effectors
of activity to measure and manipulate MLI responses in vivo during a motor-learning behavior: adaptation of the
vestibulo-ocular reflex (VOR). This will allow us to determine if learning alters how MLIs are activated during
sensorimotor stimulation and if their inhibitory output is necessary for pattern changes in Purkinje cell spiking
and the expression of learned eye movements. In the second aim, quantitative measurements from cerebellar
slice preparations of mice that gave undergone VOR learning will be used to determine if MLIs show activity-
induced plasticity in their synaptic properties. This study encompasses an innovative, multidisciplinary approach
to decipher the cellular- and circuit-level mechanisms that allow the cerebellum to encode memories of motor
learning and implement adaptive motor behavior. Completion of these aims will contribute to novel insights into
understanding how the cerebellum stores and recalls memories of learning.