The influence of protein kinases and microtubule binding proteins on cerebellar motor learning

The cerebellum (from the latin - little brain) is located at the posterior end of the brain. It is known to be involved in vital functions like the control of heart beat and respiration and also in motor coordination, a function involving balance and equilibrium, which also requires the capacity to learn and adapt. Cerebellar motor learning and memory are at the base of the studies described in this thesis. The structure of the cerebellar cortex (the outer layers) is remarkably conserved, consisting of many equivalent modules. These modules, called micro-zones, are based around Purkinje cells. Purkinje cells are big neurons in the cerebellum with flamboyantly arborized dendrites which receive hundreds of thousands of inputs, and which transmit information of various types. Purkinje cells are very important in cerebellar function because they integrate signals and respond to them by selectively changing the strength of responses. This phenomenon is called plasticity. It involves a long-lasting reduction of currents evoked at synapses (or neuronal contacts) at the Purkinje dendrites, termed long-term depression or LTD. Purkinje cells are the only neurons in the cerebellar cortex that exert a direct action on targets outside the cortex and LTD in this system is thought to permit a rapid adjustment of responses (i.e learning) to ongoing movements. In this thesis two stimuli are mainly studied, eye blink conditioning and locomotion. Specific areas of the cerebellum (area HVI in the lobule simplex as well as its related interposed deep nuclei), have been identified as sites of convergence for stimuli related to eye-blink conditioning. For the control of locomotion, the cerebellar areas involved are less well defined. In eye blink conditioning paradigms the stimulus is an air puff to the eye, which evokes a reaction, namely eye closure. If an air puff is preceded by a sound (like a warning), the animal will learn to interpret the sound; the result will be a reduction of the activity of the involved PCs in a perfectly timed manner to ensure appropriate closure of the eye when the air puff is expected. Like eye blink conditioning, locomotion paradigms often contain a learning element as well. Animals are trained and evaluated in sessions that may take several days.