Objective
Glutamate is the major excitatory neurotransmitter mediating communication between neurons in the brain. In the cerebellum glutamatergic transmission underlies information processing, contributing to the control of movement of the body, and thereafter changes in the strength of glutamatergic synapses may allow the brain to store patterns of motor activity. Although the basic mode of operation of cerebellar glutamatergic synapses is understood, there are severe defects in our knowledge of: how the strengths of these synapses may be modulated during normal function in pathological conditions like brain anoxia and during development of the nervous system.
In order better to understand the topics outlined above, patch-clamp techniques will be used on slices of cerebellum in vitro to study the fundamental properties of cerebellar glutamatergic synapses. In particular, the effects of the modulatory agents adenosine, arachidonic acid, enkephalin and corticotropin releasing factor on the synapses from parallel fibres and climbing fibres to Purkinje cells will be tested, with a view to understanding how the gains of these synapses are adjusted on short and long time scales. These experiments will significantly improve the understanding of information processing in the cerebellum, and may give insight into how it malfunctions in pathological conditions.