Trial-By-Trial Coding Of Instructive Signals In The Cerebellum: Insights From Eyeblink Conditioning In Mice

The cerebellum is an area of the brain that plays a crucial role in the learning of motor skills. This process involves climbing fibers, which provide teaching signals to Purkinje cells in the cerebellar cortex when perturbations occur during a movement. However, controversy has arisen over climbing fibers contribution to cerebellar learning. This is because climbing-fiber signals are described as "all-or-nothing": they fire a single burst of action potentials in response to all supra-threshold stimuli, regardless of their strength. On the contrary, motor learning is not all-or-nothing: the amount of learning is driven by the strength of perturbations. In this dissertation, I describe the experiments that I performed to unravel how climbing fibers may encode the strength of teaching signals. In Chapter 2, I present my behavioral studies in mice, which involved a simple cerebellar-dependent motor learning task, eyeblink conditioning. I show that mice take into account the strength of unexpected perturbations to adapt their movements trial-by-trial. In Chapter 3, I present a review of the previous literature and provide a hypothesis on how climbing fibers can encode the strength of teaching signals in a single trial. In Chapter 4, I present the findings of my in vivo two-photon calcium imaging experiments, which suggest climbing-fiber signals may not be all-or-nothing at the postsynaptic level. Finally, in Chapter 5 I describe the different mechanisms that we discovered for coding the intensity of teaching signals by Purkinje cells in the cerebellum of awake mice. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Biology First Advisor Javier F. Medina