High resolution microelectrode arrays for mapping and manipulation of brain microcircuits

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Understanding how the brain generates behavior is one of the major scientific challenges we are faced with. Over the last decades cellular neuroscientists have made breakthroughs studying how neurons receive input and generate trains of action potentials as well as identifying different types of neurons in ex vivo preparations. On the other hand, system neuroscientists recording from single neurons across different brain areas in awake subjects have related neuronal responses to different aspects of behavior. One issue that remains poorly investigated is how the intrinsic properties of isolated single neurons documented during intracellular recordings in brain slices translate into the intricate patterns of global, multiarea, neuronal activity documented during behavior. Our vision is that from the interaction of single neurons within small regions (microcircuits or small ensembles) intrinsic activity patterns emerge that hold the signature of that specific microcircuit. Such local intrinsic patterns then interact at the level of global networks to produce global brain patterns underlying sensory-motor processing, cognition and behavior in general. However, to test this hypothesis, one must gain access to at least three levels of exploration, single neurons, local microcircuits, and global brain networks. We currently have technologies that allows us to explore single neurons and entire brain networks. However, the exploration of local microcircuits has been challenging. Microcircuits consist of interconnected brain cells (neurons) within a brain area or region (i.e., local ensembles) that generate signals encoding the features of sensory stimuli, motor commands and cognitive states. It has been difficult to explore them in detail due to the lack of spatial and temporal resolution of so far available techniques. This proposal aims at acquiring a novel technology for electrophysiological experiments that allows high temporal and spatial resolution recordings and manipulation of neuronal activity in specific brain microcircuits. Our team (Martinez-Trujillo, Inoue, Muller, Allman, Schmid and Laviolette) will leverage a new, high-channel-count system to measure the electrical activity from thousands of cells and generate stimulation patterns in brain slices and organoids (brain tissue derived from stem cells) to answer questions on the role of specific microcircuits in the computations performed by the brain. Using this system, we will be able to link single neuron activity to microcircuit dynamics and unravel the spatiotemporal patterns of activity that contribute to the specific areas role in the  global neural codes used underlying behaviour. The technology will substantially synergize with existing expertise and generate collaborations amongst different investigators within our group and the Western community. Furthermore, it will enhance our ability to understand ourselves, to foster new technologies, and to train highly qualified scientists.