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. PUBLIC HEALTH RELEVANCE: The cerebral cortex is the part of the brain most implicated in cognitive brain function and in a diseased state with neuropsychiatric disorders. How information is processed in this complex network of billions of neurons is yet poorly understood, partly due to a lack of appropriate experimental tools to investigate the complex orchestration of activities in individual neurons, which generate the network activity that produces normal behavior. This proposal is to develop and improve an experimental tool that will allow us to address these essential questions using digital light processing technology to mimic network activity patterns of arbitrary complexity and their effects on individual cells and network activity.