The cerebellum plays an essential role in both the performance and plasticity of motor behavior. We try to establish a link between the processes that occur on a molecular, electrophysiological, and behavioral level. To that means we do experiments in healthy humans, patients and in animal models.Our first goal is to crack the complex spike code. Complex spikes are action potentials in cerebellar Purkinje cells that result form olivar input through climbing fibers. They are thought to encode performance error, and lead to plasticity (LTD) at the parallel fiber-Purkinje cell synapses. In rabbits we investigate what code is exactly carried by the climbing fibers, and how this code is generated.

Our second goal is to investigate the relation between LTD and motor learning. We do this by studying the learning behavior in patients and experimental animals that have a putatively altered cerebellar plasticity. This alteration is either induced genetically (genetic patients and knockout mice) or immuno-chemically (PCA-patients and mice injected with PCA-antibodies). Our current patient studies in this respect include Williams syndrome, and paraneoplastic cerebellar ataxia. Furthermore we investigate whether motor plasticity at the behavioral level obeys the learning rules that are set by LTD. Our third goal is to investigate the effect of neck injury (RSI, Whiplash) on eye-head movements.

Within the Erasmus department of Neuroscience, our group works in close collaboration with the group of Jos van der Geest, and the group of Chris de Zeeuw

Selected Recent Publications (pubmed):

• Montfoort I, Van Der Geest JN, Slijper HP, De Zeeuw CI, Frens MA.  Adaptation of the Cervico- and Vestibulo-Ocular Reflex in Whiplash Injury Patients. J Neurotrauma. 2008
• Montfoort I, Frens MA, Koes BW, Lagers-van Haselen GC, de Zeeuw CI, Verhagen AP.  Tragedy of conducting a clinical trial; generic alert system needed. J Clin Epidemiol. 2008 1(5):415-8
• Schraa-Tam CK, van der Lugt A, Smits M, Frens MA, van Broekhoven PC, van der Geest JN.  fMRI of optokinetic eye movements with and without a contribution of smooth pursuit. J Neuroimaging 2008 18(2):158-67.
• Richter JM, Slijper HP, Over EA, Frens MA.  Computer work duration and its dependence on the used pause definition. Appl Ergon. 2008 39(6):772-8.
• Schraa-Tam CK, van der Lugt A, Frens MA, Smits M, van Broekhoven PC, van der Geest JN. An fMRI study on smooth pursuit and fixation suppression of the optokinetic reflex using similar visual stimulation. Exp Brain Res. 2008 185(4):535-44.
• Slijper HP, Richter JM, Smeets JB, Frens MA. The effects of pause software on the temporal characteristics of computer use. Ergonomics. 2007 Feb;50(2):178-91.
• van Hagen JM, van der Geest JN, van der Giessen RS, Lagers-van Haselen GC, Eussen HJ, Gille JJ, Govaerts LC, Wouters CH, de Coo IF, Hoogenraad CC, Koekkoek SK, Frens MA, van Camp N, van der Linden A, Jansweijer MC, Thorgeirsson SS, De Zeeuw CI. Contribution of CYLN2 and GTF2IRD1 to neurological and cognitive symptoms in Williams Syndrome. Neurobiol Dis. 2007 Apr;26(1):112-24.
• Schonewille M, Khosrovani S, Winkelman BH, Hoebeek FE, De Jeu MT, Larsen IM, Van der Burg J, Schmolesky MT, Frens MA, De Zeeuw CI. Purkinje cells in awake behaving animals operate at the upstate membrane potential. Nat Neurosci. 2006 Apr;9(4):459-61
• Winkelman B, Frens M. Motor coding in floccular climbing fibers. J Neurophysiol. 2006 Apr;95(4):2342-51.
• Montfoort I, Frens MA, Hooge IT, Haselen GC, van der Geest JN. Visual search deficits in Williams-Beuren syndrome. Neuropsychologia. 2007 Mar 14;45(5):931-8.
• Montfoort I, Kelders WP, van der Geest JN, Schipper IB, Feenstra L, de Zeeuw CI, Frens MA. Interaction between ocular stabilization reflexes in patients with whiplash injury. Invest Ophthalmol Vis Sci. 2006 Jul;47(7):2881-4.
• Hoebeek FE, Stahl JS, van Alphen AM, Schonewille M, Luo C, Rutteman M, van den Maagdenberg AM, Molenaar PC, Goossens HH, Frens MA, De Zeeuw CI. Increased noise level of purkinje cell activities minimizes impact of their modulation during sensorimotor control. Neuron. 2005 Mar 24;45(6):953-65.
• Coesmans M, Smitt PA, Linden DJ, Shigemoto R, Hirano T, Yamakawa Y, van Alphen AM, Luo C, van der Geest JN, Kros JM, Gaillard CA, Frens MA, de Zeeuw CI. Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Ann Neurol. 2003 Mar;53(3):325-36.