This INSPIRE award brings together research areas traditionally supported by the Biophotonics and Nanobiosensing programs in the Chemical, Bioengineering, Environmental, and Transport Systems Division (CBET) of the Engineering Directorate (ENG); the Neural Systems program in the Integrative Organismal Systems (IOS) Division of the Biological Sciences Directorate(BIO); the Cognitive Neuroscience program in the Behavioral and Cognitive Sciences Division (BCS) of the Social, Behavioral and Economic Sciences Directorate (SBE); the Physics of Living Systems program in the Physics Division of the Mathematical & Physical Sciences Directorate (MPS).
Significance The formation of connections in the human brain is driven by experience. Particularly in development, but also in adulthood, repeated activity leads to lasting changes at the synaptic level. Understanding the mechanisms behind synapses formation and modification remains a fundamental question in neuroscience. To enable novel experiments that will expand our basic understanding of plasticity, the PIs propose to create and test bioelectronics systems designed specifically for neuroscience experiments. This approach is transformative because it sheds the usual constraints applied to bioelectronics systems, which are almost uniformly designed for human use. By focusing from this beginning on the need for systems to enable novel, fundamental neuroscience experiments, this interdisciplinary team will create bioelectronics implants optimized for investigating basic questions underlying plasticity.
An ultraminiaturized bioelectronics system capable of both stimulation of and recording from nerve cells will be utilized. The system will feature novel approaches to integrated circuit design, wireless operation information transfer, microelectromechanical systems for integration of the circuit with tissue, and materials for improved neural interfaces. System power will be provided by a rechargeable microbattery, allowing the system to be completely implanted and the animal to be untethered and freely roaming across several meters of experimental space. These systems will allow extended periods of bioelectronic stimulation as well as multi-animal experiments. Visual cortex plasticity in response to bioelectronic retinal input will be investigated in long-term studies with frequent monitoring of visual cortex anatomy using two-photon microscopy. Different mouse knockout models that either increase plasticity or decrease plasticity will be utilized to thoroughly investigate anatomical changes driven by bioelectronic input. Experiments related to hippocampal neurophysiology will be conducted to precisely measure activity at the neural level and compare this activity to recorded behavior. From this, sophisticated multi-input, multi-output models can be created that explain the behavior.
