Objective
We will investigate how the cerebellar cortex functions, as this remains a mystery despite more than 30 years of extensive experimental investigation. Most current theories of function are based on 25 year old ideas by Marr and Albus, which are not accepted by many researchers. These early attempts to elucidate cerebellar function focused only on the patterns of connectivity in this structure, without taking into account the cellular properties of the neurons involved. Understanding how the cerebellum works is important. First, it is an essential stepping-stone in understanding the brain. If modern techniques do not allow us to unravel the cerebellum, we will certainly fail with the more complex cerebral cortex. Moreover, cerebellar disorders are part of many disabling neurological diseases. Finally, it has recently become clear that the cerebellum is involved in human cognition. Theories of cerebellar function have many applications in artificial intelligence and robot control. We have the advantage over earlier generations of being able to use innovative methods in a multi-disciplinary approach. These will include quantitative anatomical methods, intra- and extracellular electrical recordings, voltage and calcium imaging of individual cells and of network activity and computer modeling to study the transformation of pontine mossy fiber input into Purkinje cell activity. Major aims are to study mossy fiber inputs onto granule cells, properties of cerebellar interneurons, integration of parallel fiber input by the Purkinje cell dendrite and simulation of the interaction between all these components of the cerebellum. Results will be presented at meetings and in journals, but also as an on-line neuro-informatics database.
Though the cortico-pontine pathway is the largest cerebellar input, it has hardly been studied. We will map physiologically identified mossy fiber projections of pontine neurons onto the granule cell layer in detail (Oslo). Little is known about synaptic plasticity of the mossy fiber synapse, compared to the extensive knowledge of Purkinje cell synaptic plasticity. This synapse will be studied by presynaptic (London) and post-synaptic calcium imaging (Copenhagen), combined with patch-clamp recordings (Pavia) to study its long term potentiation.
The many types of cerebellar inhibitory interneurons have hardly been studied. We will perform single and dual patch-clamp recordings to characterize their firing properties in response to synaptic input (London and Jerusalem). Impaled cells will be reconstructed. Because of its complexity, synaptic integration in the Purkinje cell dendrite is not completely understood. The Antwerp group has generated several predictions, based on a detailed computer model. We will study the strength and plasticity of single excitatory and inhibitory synapses in simultaneous recordings from both pre- and post-synaptic cells and by dual dendritic recordings using artificial synaptic input (London). In a parallel effort, synaptic integration in the Purkinje cell dendrite will be studied with a novel voltage imaging technique (Tubingen).
Finally, little is known about the ensemble activity of cerebellar neurons. This will depend on the spatial spread of parallel fiber activity, which will be voltage-imaged in the isolated cerebellum preparation (Jerusalem). Using simultaneous extracellular recordings of tens of Golgi or Purkinje cells in anesthetized and awake rats, we will measure spiking rates and correlated activity in response to tactile input (Antwerp).
The experimental results will be used to build physiologically realistic computer models of the neurons, which will be incorporated into an anatomically correct network model (Antwerp). This network model will allow us to perform quantitative studies of hypotheses on the computations performed by the cerebellar cortex .
The management of information by interneurons and Purkinje cells and cell to cell communication in the cerebellum are aims of Area 4 of the Biotechnology program.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencescomputer and information sciencesartificial intelligence
- engineering and technologymaterials engineeringfibers
- natural sciencescomputer and information sciencesdatabases
- natural scienceschemical sciencesinorganic chemistryalkaline earth metals
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Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
2610 Wilrijk
Belgium