Retrograde transduction of dopaminergic cells in substantia nigra of the rhesus monkey

Abstract

Abstract Recent advances in molecular tools have changed how researchers approach selective neural modulation, especially in rodent models where germline modifications and viral vector delivery are readily optimized. However, these tools have not advanced as rapidly for nonhuman primates, despite critical need for translational gene therapy models. A key barrier is targeting specific neuronal populations in the larger primate brain with cell-type and circuit specificity. Dopaminergic neurons pose a particular challenge due to their inaccessible ventral midbrain location, where local injection non-selectively targets all dopaminergic neurons. This work provides NHP researchers with a comparison of retrograde viral vectors, highlighting one which achieves efficient dopaminergic neuron transduction, establishing a foundation for combining vectors with cell-type-specific enhancers for basic and translational applications.