Studying stimulation of long-range cortical projections involved in visual-spatial behavior in non-human primates with a novel multimodal optoelectronic device

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Irreversible blindness affects over one million people nationally and over 40 million globally, with most cases of acquired blindness leaving the visual cortex intact. A cortical visual prosthesis (CVP) is a promising therapeutic strategy for these individuals. However, the production of perceived visual sensations through stimulation of long-range cortico-cortical connections has proven to be variable and inconsistent. There is a lack in understanding of the biophysical mechanisms of cortical stimulation and its effects on neural dynamics and behavior. Investigating these mechanisms has been limited by the model system and the neuro-technologies available to interrogate that system. Projections from the posterior parietal cortex (PPC) to the prefrontal cortex (PFC) in non-human primates (NHPs) are involved with saccades in visual-spatial attention and provide an ideal and generalizable system to study long-range cortical dynamics during behavior. Retrograde adeno- associated viruses (retroAAVs) can specifically target PPC-PFC projection neurons for optogenetic stimulation. In Aim 1, a multimodal optoelectronic device with microLED and transparent microelectrodes will be developed to enable colocalized optogenetic stimulation and electrical recording of the projection neurons with high spatiotemporal resolution. In Aim 2, the retroAAV injection protocol will be optimized to achieve the highest transduction efficacy. In Aim 3, the optoelectronic device and retroAAV strategy will be implemented to introduce microstimulation of the PPC-PFC neurons in NHPs during a visual-spatial task. Our preliminary data on successful optoelectronic device development, retroAAV expression, and optogenetic stimulation and single-unit recording of PPC-PFC projection neurons reduce risk and validate feasibility for our proposal. The results will improve our understanding of the biophysical mechanisms of how stimulation affects multiregional cortical dynamics and visual behavior, informing the future development of effective CVPs.