Kainate receptor subunits in the mouse cerebellum

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Connections between neurons (called synapses) are modulated in ways that are critical for the normal functioning of the mammalian brain. The long-term goal of my research program is to identify and characterize the mechanisms that are involved in synaptic modulation in the mouse cerebellum - an area of the brain that is critical for motor co-ordination and motor learning. Glutamate is the most abundant excitatory neurotransmitter found in the central nervous system. Glutamate can activate 3 main classes of ion permeable receptors: AMPA, NMDA and kainate receptors. Although AMPA and NMDA receptors are well characterized, relatively little is known about the kainate class of glutamate receptors. Recent evidence suggests that kainate receptors may play an important role in the modulation of neurotransmission by regulating glutamate release. Recent experiments in my laboratory have shown that in the cerebellum, kainate receptors strengthen neurotransmission by increasing glutamate release at one synapse, but weaken neurotransmission by decreasing release at another synapse. Modulation of both synapses is critical for normal motor co-ordination and motor learning. The main objective of my research program is to determine how kainate receptors differentially modulate glutamate release in the cerebellum and how this modulation is important for motor behaviour. Specifically, I will use genetically engineered mice that lack one of each of the five kainate receptor subunits to test the hypothesis that kainate receptors that increase release are made up of different subunits then kainate receptors that decrease release. I will then test these mice for subtle differences in motor co-ordination and motor learning using video-based gait analysis and eye movements in the vestibular-ocular reflex . The results from this study will provide insight into how the differential subunit composition of kainate receptors regulates the balance between excitation and inhibition in the brain and how co-ordination of learned motor behaviour is generated in the mouse cerebellum.