Transgene Expression in Target-Defined Neuron Populations Mediated by Retrograde Infection with Adeno-Associated Viral Vectors

• DOI: 10.1523/jneurosci.1618-13.2013
• Publication Date: 2013-09-18T17:27:41Z
• Authors: Markus Rothermel; Daniela Brunert; Christine Zabawa; Marta Díaz-Quesada; Matt Wachowiak
• Keywords: Cre recombinase; Transduction (biophysics); Adeno-associated virus

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