R44MH118155

SUMMARY Understanding how the brain controls behavior requires studying the dynamic activity of different types of neurons in distributed neural circuits in awake behaving animals. Currently, there are few technologies available however that allow researchers to record the activity of hundreds to thousands of neurons at arbitrary depth in the brains of awake, behaving animals. While there has been much recent progress in the development of high-density micro-fabricated silicon probes, current commercially available probes offer little to no customizability to the morphology of different brain regions and different cell types within brain regions. Even more importantly, there are no commercially available solutions of high-density probes with integrated stimulation capabilities enabling causal, closed-loop experimentation. In Phase I, we designed and fabricated customizable high-density recording probes for acute head-fixed recordings and streamlined our fabrication strategies. The resulting devices had high yields of functional electrode sites and were successfully used by beta-tester labs to generate data with good signal-to-noise ratios. We furthermore built an online graphical interface where end-users can design their probes and submit their designs for fabrication. In Phase II, Neural Dynamics Technologies LLC will develop customizable, high-density probes with integrated closed-loop capabilities that can be chronically implanted for use in animals that are either head-fixed or able to move around freely. The first aim of our Phase II proposal is to integrate light delivery and electrical stimulation capabilities onto our probes to enable closed-loop experimentation. The locations for light delivery and electrical stimulation will be customizable so that customers can specify their desired location. The second aim will be to develop a packaging approach that involves building an application specific integrated circuit (ASIC) and a head-stage that can control all integrated functionalities. The combined packaged device will be small enough to enable chronic experiments in either head- fixed or freely moving animals. The third aim will be to perform both bench-top testing and in vivo animal testing of devices to establish basic functionality and effectiveness of the devices. In summary, NDT will design innovative closed-loop interfaces that will enable causal studies addressing the functional role of different brain regions and neuron types in the brains of both head-fixed and freely moving animals. These types of closed-loop devices may be further evolved into neural implants to treat neurological diseases such as refractory epilepsy, Parkinson’s and other tremor disorders.NARRATIVE Neurological disease will be a leading cause of chronic disease in the coming decades and to confront this development with effective therapeutics, we need a better understanding of the neural circuit activity that underlies both healthy and diseased brain function. To study the dynamics of neural circuit activity, technologies are required that can chronically measure the spiking activity of many individual neurons in vivo, in intact brains. Neural Dynamics Technologies develops innovative high-density implantable neural interfaces that can be customized to the morphology of different brain regions, and that offer integrated stimulation capabilities, therefore enabling causal, closed-loop and chronic recording of neural circuit activity.