Back to front: importance of cerebro-cerebellar interactions in goal-directed behaviour.

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A substantial part of animal, including human behaviour is goal-directed. Learning how to achieve a defined goal requires the interplay between higher brain centres involved in planning and decision making, and subcortical structures that co-ordinate the desired movement. The prefrontal areas of the cerebral cortex are thought to be especially concerned with the planning and decision making aspects of such tasks, while the cerebellum is heavily involved in co-ordinating the desired action. However, recent studies in humans and patients are challenging this division of labour and it is increasingly being recognised that the contribution of the cerebellum goes beyond movement control to include many other aspects of brain function, including a contribution to cognitive processes. The cerebellum is linked to structures throughout the central nervous system, from the spinal cord to prefrontal cortex. An important organizational principle of the cerebellum for understanding these widespread connections is a division into a series of anatomical/functional units called modules. How individual modules contribute to goal-directed behaviour remains far from clear. Individual cerebellar modules are thought to contain representations (internal models) of predictable behaviour that allow us, through practice, to execute tasks more rapidly and with increased accuracy. The current project uses the modular organization of the cerebellum combined with the computational capability of internal models as a structural and theoretical framework to study prefrontal-cerebellar network interactions during goal-directed behaviour.An important gap in our understanding of prefrontal-cerebellar interactions is investigation in animal models of large scale brain networks in terms of information processing at the level of recording neural population activity and spike trains of individual neurones; and also interventionist work to dissect out the functional importance of the interactions. Linking the study of higher centres to movement control also has the advantage that 'cognition' is constrained in the sense that it is being studied in relation to well defined behavioural outputs. In collaboration with our industrial partner (Takeda Cambridge Ltd) we will therefore use the combined power of multichannel electrophysiological recording, stimulation, functional anatomical and behavioural techniques at the systems level of analysis to advance our understanding of the function of brain circuits involved in goal-directed behaviour. Choice of experimental model: cerebellar network architecture and patterns of connectivity are highly conserved across mammalian species, including human. However, adult rats are the experimental animal of choice because our understanding of the basic neuroanatomy and physiology is most complete in this species. Importantly, our experiments will include study of neural network interactions during behavioural situations that have been well characterized in rats and that correlate to human cognitive performance. We will study neural network dynamics in prefrontal-cerebellar circuits during cognitive task performance before and after transcranial stimulation of the cerebellum. The latter has been shown in human studies to improve cognitive task performance but the underlying neurobiology is unknown. In complementary functional anatomical studies our industry partner will chart the pattern of neural network activation produced by transcranial cerebellar stimulation.The results of our project aim to provide fundamental new insights into how neural circuits within the brain give rise to our ability to modify our actions to achieve a particular goal.