Cerebellar-Cortical Control:
Cells, Circuits, Computation, and Clinic
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Theoretical Neurobiology Group |
We study the physiology and function of the cerebellum and cortex employing a combined theoretical, technological and experimental approach. To support the computer modeling, data analysis and interpretation we also develop software tools. Our research is a combination of neurophysiology and neuroinformatics / computational neuroscience.
With emphasis on the specific goals and milestones of the C7 network, at the cellular level we are developing a new Purkinje cell computational model using automated parameter search methods. This model will be used to study the effect of channel modulation on excitability and its interaction with synaptic input. We are also developing a new, large network model of the cerebellum, including the olivary nucleus. We will use this network model to simulate cerebellar information processing as observed during functional imaging experiments and to study the role of distributed synaptic plasticity in cerebellar learning.
Our experimental work consists of electrophysiology on in vitro brain tissue slices and cell cultures and in vivo recordings in anesthetized or awake rodents. New approaches currently under development are current source density analysis methods to study the dynamics of synaptic signalling in neuronal microcircuits, the use of micromachined substrates and conductive nanoparticles coating to enhance neuron-electrode performance and stability, and noisy stimulation techniques to study the input-output relation of neurons. During the activities planned for the C7 network, we will apply these techniques both in vitro (Golgi cells) and in vivo (Golgi, Purkinje and DCN neurons).
Our experience with noisy stimulation protocols recently led to a novel way to characterize the stationary as well as the dynamical response properties of individual neurons, allowing one to quantify in an extremely compact way some of the electrophysiological blueprint of neuronal exctiability and to unveil previously underestimated neuronal firing dependences on the input.
Patch clamp of cerebellar neurons in in vitro slice is also used to study the synaptic plasticity of Golgi cells.We have implemented single-cell PCR techniques to investigate simultaneously the electrophysiology and molecular composition of voltage-gated channels in neurons. This technique is being used to investigate the change in expression of potassium channel expression in Purkinje cells during development.