PROJECT SUMMARY/ABSTRACT A major obstacle to understanding how the dynamic activity of brain circuits permits the emergence of cortical function is the insufficient capability to acquire and manipulate this activity across the course of brain maturation. Neuromodulators and neural activity patterns are intimately linked in mediating this maturation. There is an urgent need to develop technology to acquire and manipulate neurophysiological signals from small, fragile, immature brains and address this gap in knowledge. Our long-term goal is to causally determine neural correlates of cognitive functions and neuropsychiatric disorders in the developing brain. Here, we step toward this goal by pursuing the overall objective of this project: to establish a fully implantable closed-loop neural interface device that can detect neurophysiologic signals and responsively deliver neurochemicals in mouse pups as they grow and develop. Our central hypothesis is that integrating conducting polymer electrodes, conformable ionic circuits, and organic ion pumps will enable the creation of an Organic Closed-loop Electrochemical Array for Neurodevelopment (OCEAN) that will help us elucidate the coordination of neural activity and neurochemistry in the developing brain. This hypothesis is supported by preliminary data demonstrating the use of i) conformable high-density surface electrocorticography arrays (NeuroGrids) to record from cortical networks in developing rodents; ii) conformable, biocompatible ionic circuits capable of processing neurophysiological signals; iii) highly conductive, stretchable, flexible materials for transmission of such signals; iv) organic ion pumps to modulate brain signals with millisecond precision. The rationale for the proposed research is that integration of these materials and devices will enable us to address the substantial barriers that essentially preclude chronic, high spatiotemporal monitoring and manipulation of neural networks in vivo during development. The specific aims include: (i) establish expandable, conformable, and biocompatible integrated components for high spatiotemporal resolution electrophysiologic monitoring; (ii) establish expandable, conformable, and biocompatible integrated components for high spatiotemporal resolution neurochemical modulation; (iii) integrate neurophysiologic recording and neurochemical delivery to perform proof-of-concept closed-loop modulation. The proposed research is innovative, in our opinion, because it uses organic electronic approaches at all stages – signal acquisition, processing/detection, data transmission, device powering, and neurochemical delivery to create for the first time a fully implantable responsive neural interface device compatible with in vivo use in naturally behaving rodents across development. This work is expected to be significant because it will provide the groundwork for interacting with neural networks across periods associated with brain maturation and the ...