Intersectional targeting of defined neural circuits by adeno-associated virus vectors

The mammalian nervous system is a complex network of interconnected cells. We review emerging techniques that use the axonal transport of adeno-associated virus (AAV) vectors to dissect neural circuits. These intersectional approaches specifically target AAV-mediated gene expression to discrete neuron populations based on their axonal connectivity, including: (a) neurons with one defined output, (b) neurons with one defined input, (c) neurons with one defined input and one defined output, and (d) neurons with two defined inputs or outputs. The number of labeled neurons can be directly controlled to trace axonal projections and examine cellular morphology. These approaches can precisely target the expression of fluorescent reporters, optogenetic ion channels, chemogenetic receptors, disease-associated proteins, and other factors to defined neural circuits in mammals ranging from mice to macaques, and thereby provide a powerful new means to understand the structure and function of the nervous system.