Control of cell fate and excitability at the neural electrode interface: Genetic reprogramming and optical induction

The development of implantable microelectrode arrays (MEAs) to deliver therapy by recording or stimulating electrical pulses in neural tissue has created a renaissance in the treatment of neurological disorders and the study of the brain. However, following implantation, a reactive tissue response causes a shift in the cellular constituency interfaced by devices: neuronal signal sources are displaced by encapsulating glial cells. We are developing novel applications of genetic engineering to control the identity of cells interfaced by implanted electrodes and restore neuron-device communication. We are pursuing two strategies to redefine the connection between specific electrode sites and individual subtypes of neurons: (1) the use of replication-deficient viral vectors to reprogram the identity of glia encapsulating the device toward neurons of specific identities, drawing from recent advances in cellular reprogramming, and (2) the use of optical induction of proneural genes to alter cell fate at the interface of implanted optoelectrode probes. Our data indicate successful conversion of non-spiking glia to functional neurons via the overexpression of fate-specifying genes (Ascl1, Dlx2) as well as the use of an optical induction system to drive proneural gene expression. The endgoal is a fully-integrated abiotic-biotic interface capable of “tapping into” the electrical signals generated by specified brain circuitry.