Molecular Mechanisms Underlying Associative Learning

This thesis primarily attempts to solve some long standing issues regarding classical eyelid conditioning. More specifically, what is the specific role of cerebellar LTD in classical eyeblink conditioning, and how does the answer change the view on cerebellar functioning on associative motor learning. The approach used in this thesis is a combination of the above mentioned genetic approach with classical conditioning experiments. The genetic techniques are by far best possible in mice because of their fast breeding and the availability of genetically well characterized inbred strains. Often gene function is tested by creating transgenic or knockout mice. In transgenic mice, artificial DNA is introduced in the genome of a mouse, which will lead to expression of the transgene in the adult animal. In knockout mice a targeted gene is completely deleted from the genome. The protein that was coded by this gene will no longer be expressed. To be able to study the effect of genetic lesions on classical conditioning we needed a system that could reliably measure the performance of a mouse on such a learning task. Some studies using mice in eyeblink conditioning tasks already existed. All these studies used electromyographic (EMG) recordings of the MOO muscle to assess responsiveness on the training paradigm. Attempts to repeat this procedure led to the realization that to obtain reliable EMG recordings of the MOO muscle in a mouse over a number of consecutive days is close to impossible, simply because of the small size of a mouse eyelid. We therefore developed a new system that could reliably measure eyelid position over time in mice. Since it makes use of magnetism we called it the magnetic distance measurement technique (MDMT).