The proposed research will contribute to the understanding of how the cerebellar cortex integrates mossy fiber input into Purkinje cell output. The approach to be taken includes both the construction of a detailed compartmental model of a single Purkinje cell and the large scale simulation of a realistic network model of cerebellar cortical circuitry. Both types of models will be run on a parallel supercomputer. All modeling results will be related to ongoing physiological investigations in the lab. The detailed compartmental model of the Purkinje cell will be constructed from morphological and electrophysiological data obtained from the rat cerebellum. This model will first be used to study the processing of random parallel fiber synaptic inputs examining interactions between asynchronous and synchronous inputs. We will then explore which synaptic mechanisms could underlie prolonged synaptic depolarizations we have found to follow granule cell activation. These simulations will first be performed on a model with relatively simple calcium dynamics. However, the modeling effort will then be extended to include detailed modeling of calcium diffusion and buffering. These results will be directly relevant to current discussions of parallel fiber synaptic plasticity including the effects of long term depression on synaptic integration. The second phase of these experiments involves the incorporation of the modeled Purkinje cell as well as other neurons in the cerebellar cortex into a large scale network model of folium crus IIa of the rat cerebellar cortex. This model will be closely based upon known structural and physical properties of this region of the cerebellum and will produce neuron-like outputs that can be compared to data from actual physiological experiments. With this network model we will explore how Purkinje cells react to realistic patterns of parallel fiber synaptic inputs generated by the tactile mossy fiber projections to this cerebellar region. Ultimately, we hope to determine how the detailed patterns of these fractured tactile maps shape overlying Purkinje cell firing patterns.
| Jaeger, D; De Schutter, E; Bower, J M (1997) The role of synaptic and voltage-gated currents in the control of Purkinje cell spiking: a modeling study. J Neurosci 17:91-106 |
| De Schutter, E; Bower, J M (1994) An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses. J Neurophysiol 71:401-19 |
| De Schutter, E; Bower, J M (1994) Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs. Proc Natl Acad Sci U S A 91:4736-40 |
| De Schutter, E; Bower, J M (1994) An active membrane model of the cerebellar Purkinje cell. I. Simulation of current clamps in slice. J Neurophysiol 71:375-400 |
