Regenerative Electrode Interface

Erin K. Purcell | |


Research in the Regenerative Electrode Interface Laboratory is focused on improving and redefining the connectivity of electrode arrays implanted in the brain with the neural circuitry that they are intended to interface.  Neural prostheses are microelectrode arrays that record or stimulate the electrical activity of nearby neurons following implantation in the brain.  In a lab setting, these devices are used to understand the role of neural activity in a variety of neuroscience research applications. In the clinic, they can be used to restore sensory and motor function for patients suffering from the debilitating effects of neurological injury and disease.  For either application, stable, sustained electrical communication between the implanted electrode surface and a large sample of local neurons is desired.  However, poor integration of the device with the surrounding neural tissue remains a significant unsolved problem that limits the long-term function of neural prostheses.

Our research goals are to characterize the integration of implanted electrodes with the neural tissue they record or stimulate and develop approaches to improve the fidelity and patency of the interface. In the long-term, we envision connecting individual electrode sites with specific neuronal subtypes.  Our approaches include a combination of regenerative scaffolding, optogenetics, histology and electrophysiology.  Our current projects include:

Optical control of network formation in stem cell-derived neurons

We are exploring ways to use light as a cue to build neural circuits from the “ground up.” Our approaches include the use of optogenetics to selectively strengthen or weaken synaptic connectivity between subpopulations of neurons via spike timing-dependent plasticity and optical induction of gene expression through the delivery of photosensitive transcription factors to mammalian cells.  For the latter approach, we are exploring spatial patterning of proneural gene expression as a method to derive neuronal circuitry from stem cells.  We have recently collaborated with Dr. Nelson Sepúlveda’s lab to further fine-tune the spatial precision of the optical stimulus using a motorized micromirror system.  Likewise, we are collaborating with Dr. Wen Li’s lab to lay the foundation for a future application of this work in vivo.

Plasticity in the electrical properties of neurons surrounding neuroprostheses

A key difficulty in analyzing and decoding neural activity generated by the brain is the instability of recorded neuronal signals, which occurs on both short (intra-day) and long (inter-day) timescales.  The underlying cause of this instability is unclear, and we believe that plasticity in the intrinsic excitability of interfaced neurons plays a key role in this.  We are developing a novel preparation combining extracellular and intracellular recordings, in addition to routine quantitative histology, to explore this hypothesis.  We are collecting data over several weeks post-implantation to assess the impact of neuroprostheses on surrounding ion channel expression and synaptic remodeling.

Reprogramming and rewiring the neural-electrode interface

We are exploring new approaches to use genetic engineering to understand and control the interface between neurons and electrodes. Using such approaches, it may be possible to tune the response properties and prescribe the network architecture of neurons at the neural prosthesis interface, improving the function of both recording and stimulating devices and the integration of a synthetic substrate with living brain tissue.