MULTICHANNEL ELECTROPHYSIOLOGICAL RECORDING FROM CELL ASSEMBLIES IN GENETICALLY MODIFIED BRAIN CIRCUITS

Despite impressive advances in every field of neuroscience, our understanding of brain function remains largely confined to its building blocks at the microscopic level, and to phenomenological descriptions at the macroscopic level. The introduction of tr ansgenic mice has provided neuroscience with countless correlations between microscopic and macroscopic levels, but because most gene knockouts have lacked regional and temporal specificity, insights into computational mechanisms remain scarce. Understand ing how complex mental functions originate from electrical and chemical processes in brain cells requires a comprehensive systems-biological analysis focused on the intermediate level of neuronal microcircuits, where myriads of intricately connected neuro ns act together. Microcircuit computations could be comprehended if it were possible to record neural activity in animals with genetic interventions restricted to particular brain regions and cell-types. Technologies for such interventions have been devel oped recently. The aim of this project is to exploit the recent developments to set up a new lab for addressing functions of neuronal microcircuits in a mammalian species large enough to carry electrode arrays for simultaneous recording from several tens of channels during behaviour. Using the rat's spatial representation system as an experimental model, we shall record activity from large cell populations in the hippocampus and entorhinal cortex after virus-based introduction of transgenes that silence o r activate the target cells. Because these experiments will be performed in a new laboratory for recording in extended spatial environments, we apply for funding to cover the costs of a large-scale modular open field arena, a new telemetric recording syst em for use in this environment, and the molecular tools required to develop the viral vectors required to selectively manipulate key cell types of potential importance for navigation in large spatial environments.