Manipulation and imaging of synchronous population activity in the neocortex

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DESCRIPTION (provided by applicant): Understanding neuronal information processing and neuronal communication in massively interconnected networks like the neocortex is one of the great challenges of neuroscience. At the center of an ongoing debate about information processing in the neocortex is the question about the nature of the neuronal code used in the neocortical network, i.e. whether spike rates or precisely timed synchronous spike patterns carry and process information. There is substantial experimental evidence supporting the functional significance of synchronous spiking activity. Synchronized spikes have been shown to encode motor events, to represent visual, auditory and gustatory sensory information and to correlate with cognitive functions such as attention. However, the neurophysiological mechanisms underlying synchronized neocortical activity are only poorly understood. Two important open questions are: How sensitive are cortical neurons to synchronous synaptic inputs? When and how does synchronous activity propagate through the cortical network? Currently, most of our knowledge about the generation and propagation of synchronous neocortical activity is based on theoretical studies, as experimental approaches in biological networks have been technically challenging. Here we propose a powerful new optical approach to investigate the neurophysiological bases of synchronized activity in the neocortex. The approach uses our newly developed digital light processing (DLP)-based dynamic photo- stimulation system that allows the spatiotemporal control of in vitro cortical network activity using 786,000 independently controlled photo-stimulation sites. Dynamic photo-stimulation will be combined with voltage sensitive dye (VSD) imaging and intracellular electrophysiological recordings to monitor individual neuronal responses and the propagation of synchronized and un-synchronized population activity in the in vitro cortical network. The neurophysiological bases of human cognitive disorders such as schizophrenia or autism spectrum disorders are only poorly understood. A yet unexplored possibility is that the neocortical network's ability to generate, process and propagate synchronous population activity - which is believed to play a key role in higher cortical functions - is altered. Our approach provides new opportunities to investigate potential pathological changes in the processing of synchronous neuronal events in mouse models of human cognitive disorders. This might lead to valuable new insights into the neuropathology of cognitive disorders and inspire new treatment strategies.