Some types of associative learning processes belong to the simplest forms of learning, yet the underlying mechanisms are still surprisingly complex. In our lab we use classical conditioning procedures to analyze the underlying mechanisms behind these associative learning processes on the behavioral, cellular and molecular level. We are especially interested in the role of the cerebellum in these processes.

We focus on three “main” directions:

1. Blink reflex recording and conditioning in normal and transgenic mice; we developed a method to record eyelid movements (MDMT) in freely moving mice. With this method we study if, and how various transgenic mutant mice (e.g Fragile X) differ from wild types in an attempt to localize critical molecular components of the eyeblink conditioning mechanism.
2. Blink reflex recording and conditioning in humans; In healthy volunteers and a variety of patients we’ll start to measure the blink reflex and conditioning of the blink reflex with the use of the MDMT system
3. Cerebellar cortical imaging during conditioning tasks; We use high speed optical imaging of autofluorescence signals that are coupled to neuronal activity on the surface of the cerebellum. Our intend is to couple this imaging technique to classical conditioning procedures in mice, in order to study changes in neuronal population activity during these learning processes.

Selected recent publications

• Koekkoek, S.K., et al., Cerebellar LTD and learning-dependent timing of conditioned eyelid responses. Science, 2003. 301(5640): p. 1736-9.
• Kistler, W.M., et al., Analysis of Cx36 knockout does not support tenet that olivary gap junctions are required for complex spike synchronization and normal motor performance. Ann N Y Acad Sci, 2002. 978: p. 391-404.
• Koekkoek, S.K., et al., Monitoring kinetic and frequency-domain properties of eyelid responses in mice with magnetic distance measurement technique. J Neurophysiol, 2002. 88(4): p. 2124-33.
• Hoogenraad, C.C., et al., Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nat Genet, 2002. 32(1): p. 116-27.
• Sun, J.C., et al., Origin of vestibular dysfunction in Usher syndrome type 1B. Neurobiol Dis, 2001. 8(1): p. 69-77.