Here, we have employed bacTRAP translational profiling and virus mediated trans-synaptic tracing studies (Wall et al., 2010) to demonstrate that the Wolfram syndrome gene (Wfs1) is expressed in a specific population of neurotrophin 3 (Ntf3) and proenkephalin (Penk1) expressing pyramidal cells in superficial layer 2/3 of the mPFC. The gene discussed is NTF3; the disease is Down syndrome.