Modified neuroinvasive viruses can be used to determine neuron connectivity
(A) Directionality of spread of transsynaptic viral tracers. Schematic of anterograde spread of herpes simplex virus 1 H129 (HSV-H129), and retrograde spread of the Bartha strain of pseudorabies virus (PRV-Bartha) and the N2c strain of rabies which is glycoprotein deleted (Rb N2c ΔG). H129 and PRV-Bartha spread continuously across a chain of synaptically connected neurons, while spread of Rb N2c ΔG requires the trans-complementation of the missing glycoprotein in each cell. Adeno-associated virus (AAV) usually does not spread transsynaptically and is shown for comparison.
(B) Various viral expression levels across a network of connected cells, including local interneurons. Viral expression levels vary continuously along synaptically-connected neurons. The continuous distribution requires consideration of the amount of fluorescence that constitutes a positively infected cell.