Tools enabling the manipulation of well defined neuronal subpopulations are 
critical for probing complex neuronal networks. Cre recombinase (Cre) mouse 
driver lines in combination with the Cre-dependent expression of proteins using 
viral vectors--in particular, recombinant adeno-associated viral vectors 
(rAAVs)--have emerged as a widely used platform for achieving transgene 
expression in specified neural populations. However, the ability of rAAVs to 
further specify neuronal subsets on the basis of their anatomical connectivity 
has been reported as limited or inconsistent. Here, we systematically tested a 
variety of widely used neurotropic rAAVs for their ability to mediate retrograde 
gene transduction in the mouse brain. We tested pseudotyped rAAVs of several 
common serotypes (rAAV 2/1, 2/5, and 2/9) as well as constructs both with and 
without Cre-dependent expression switches. Many of the rAAVs tested--in 
particular, though not exclusively, Cre-dependent vectors--showed a robust 
capacity for retrograde infection and transgene expression. Retrograde 
expression was successful over distances as large as 6 mm and in multiple neuron 
types, including olfactory projection neurons, neocortical pyramidal cells 
projecting to distinct targets, and corticofugal and modulatory projection 
neurons. Retrograde infection using transgenes such as ChR2 allowed for optical 
control or optically assisted electrophysiological identification of neurons 
defined genetically as well as by their projection target. These results 
establish a widely accessible tool for achieving combinatorial specificity and 
stable, long-term transgene expression to isolate precisely defined neuron 
populations in the intact animal.