Engineered viral vectors for functional interrogation, deconvolution, and manipulation of neural circuits

Optimization of traditional replication-competent viral tracers has granted access to immediate synaptic partners of target neuronal populations, enabling the dissection of complex brain circuits into functional neural pathways. The excessive virulence of most conventional tracers, however, impedes their utility in revealing and genetically perturbing cellular function on long time scales. As a promising alternative, the natural capacity of adeno-associated viral (AAV) vectors to safely mediate persistent and robust gene expression has stimulated strong interest in adapting them for sparse neuronal labeling and physiological studies. Furthermore, increasingly refined engineering strategies have yielded novel AAV variants with enhanced target specificity, transduction, and retrograde trafficking in the CNS. These potent vectors offer new opportunities for characterizing the identity and connectivity of single neurons within immense networks and modulating their activity via robust delivery of functional genetic tools.