Contact:
Prof. C.I. de Zeeuw
Department of Neuroscience
Erasmus MC
Dr. Molewaterplein 50
3015 GE Rotterdam
P.O. Box 2040
3000 CA Rotterdam
The Netherlands
Computer models as an aid for better understanding of the olivo-cerebellar system
The work done in the De Zeeuw lab focuses mainly on teasing out the function of the cerebellum's circuitry at the cellular level. One main track of research in the SENSOPAC framework revolved around the role of the inferior olivary nucleus (IO) in cerebellar functioning. The IO provides one of the two main inputs to the cerebellum: the so-called climbing fibers. Climbing fiber activation has a profound effect on the firing behavior of cerebellar Purkinje cells and has been strongly implicated in cerebellar learning and timing.
The neurons of the IO have some highly interesting properties that set them apart from most other neurons: they have a very low discharge rate (1-2 Hz under normal conditions, with rates up to 10 Hz achieved under the effect of harmaline), have a membrane potential that shows slow sub-theshold oscillations (3-10 Hz) and are extensively interconnected through dendro-dendritic electrical synapses made up of the connexin-36 protein. In order to investigate IO network properties and its effects on cerebellar learning, one would ideally record from the intact nucleus. Unfortunately, this is technically very difficult due to the exact location of the IO in the brain.
In order to assess the implications of the properties of single IO cells on a network level, results from previously conducted whole-cell recordings were used to improve an existing highly detailed two-compartmental IO cell model, representing the neuron's soma and dendrite individually. This model was then used to study network dynamics and make predictions concerning effects on cerebellar learning with and without electrical synapses in the IO (e.g. how the learning of aspects concerning timing is impaired when connexin-36 is not expressed in the IO).
New findings about the IO are still being made and the model used is being improved and expanded accordingly. Models of other parts of the olivo-cerebellar system also exist. New findings about learning and underlying plasticity rules shape the way we think about the interaction between cells in the olivo-cerebellar circuitry. Building on current knowledge, we steadily work to build what may ultimately become an artificial cerebellum.
