INTRICA · Development and Neuromodulation of Intrinsic Cortical Activity

We propose to study intrinsic cortical network activity in-vitro. It is already known that the cerebral cortex, both in-vivo and in-vitro, produces spontaneous patterns of electrical activity independently of extrinsic inputs. These consist of network-induced prolonged depolarizations & action potentials (UP states), alternating with periods of synaptic withdrawal, membrane hyperpolarization and cessation of firing (DOWN states). It is precisely on such endogenous activity that all external inputs act, namely sensory information and/or neuromodulation. It is also increasingly evident that certain mental disorders are associated, not with specific brain lesions or cellular degeneration, but with abnormal cortical activity. Hence, this endogenous activity is crucial for our understanding of cortical information processing. To present, the generation and development of intrinsic discharge patterns and their interaction with external inputs are poorly understood. Here we propose to use brain slices to study the ontogeny and susceptibility to neuromodulation of spontaneous slow oscillations (UP/DOWN states) and persistent activity (evoked UP states) of different cortical regions. We will first compare the development of spontaneous slow oscillations in distinct cortical areas, from prenatal ages to adulthood. This is a novel and essential first step towards understanding the functional differentiation of the cortex, and identifying the possible onset of abnormal network activity during disease. We will then examine how neuromodulators, that gate distinct information processing brain states, affect spontaneous and evoked UP states in thalamocortical slices from adult animals. These data will help clarify how behaviourally distinct brain states affect intrinsic cortical dynamics. This grant will enable the applicant, a worldwide expert in this in-vitro model, to bring the know-how to Europe and continue his training and research in the European Community.