Inducible expression of retrograde transynaptic genetic tracer in mice

A key step towards understanding the development and function of the central nervous system is by characterizing the connections between neurons. Tetanus toxin C fragment (TTC) is transynaptically and retrogradely transported without the toxin's pathogenic effect, and therefore, recently it has been used as a genetic tracer combined with β-galactosidase or green fluorescent protein. Here, we introduce a new fusion construct, APTTC, consisting of the truncated human placental alkaline phosphatase with TTC, and generating the transgenic mouse line, (tetracycline operator) tetO-APTTC, for inducible expression of APTTC regulated by tetO. We demonstrate that APTTC is transported retrogradely and transynaptically, and allows us to robustly visualize the inputs of the expressing neurons when transgenetically expressed in mice, exemplified in the striatal neuronal circuit. Therefore, tetO-APTTC transgenic mouse line can be widely used for visualization of neuronal connectivity when combined with mice carrying tetracycline-controlled transactivator (tTA) in any specific neurons.