NeuroVentures Funded Grant

Craig Garner, Psychiatry
Nick Melosh, Materials Science & Engineering
John Huguenard, Neurology
Krishna Shenoy, Electrical Engineering

Interconnected networks of cells in the brain called neurons underlie all cognitive functions. Communication between neurons occurs through electrical signals. Key advances in our understanding of brain function during the last several decades have resulted from technologies that permit monitoring of this electrical activity in neurons. This technique, broadly referred to as electrophysiology, permits the study of circuits of connected neurons responsible for sensation, movement, thought, learning, and memory. These techniques have also revealed how abnormal electrical signaling between neurons can lead to dysfunction as occurs in disorders such as Autism or Alzheimer’s disease as well as due to damage from a stroke or injury. The most sensitive form of electrophysiological recording monitors very small electrical currents in single cells with glass pipettes placed inside the neuron. These ‘intracellular’ recordings are a powerful tool for exploring how neurons work– and don’t work – at the level of molecules, genes, and biochemical pathways. By studying neurons in this careful manner, scientists have been able to discover specific causes of dysfunction in disease – for instance due to the abnormal function of one protein – and discovered drugs that can target these abnormalities. Despite these great advances, intracellular recording technology has significant limitations: puncturing the cell damages it, leading to short recordings and abnormal properties; skilled scientists are required, reducing the number of labs that can use this technique; and recording from more than one or two neurons at the same time is rarely possible, making it challenging to study how neurons communicate with each other.

To address these limitations, our multi-disciplinary group of biologists, material science engineers, and neuroscientists is developing a fundamentally new way to record intracellularly from neurons. Using silicon wafer microfabrication, team members have developed a new system for intracellular neuron recordings. Rising from the silicon wafer are small electrically-active posts engineered to fuse with the cell membrane, providing a tight electrical seal appropriate for electrical recordings that are stable for days to weeks. Conceptually, this arrangement allows for an intracellular whole cell patch-clamp system with hundreds or thousands of electrodes that supports non-destructive electrical access into neuronal cells. Our long-term goals are to develop this technology for wide distribution among researchers to advance basic discoveries and accelerate drug discovery to improve the health and well-being of those suffering from disorders of the brain.