Previously (SFN 2004) we reported the identification and expression pattern of zfSIDT2, an avian homolog of a gene involved in the transport of small double-stranded RNA molecules and systemic RNA interference. zfSIDT2 transcripts are present in the songbird brain at extremely low levels, with expression in the forebrain restricted to HVC, RA, medial and lateral MAN, and the hippocampus. We find that sites of zfSIDT2 expression in the brain coincide with the propensity of neurons in these regions to take up dsRNA, as judged 24hrs after injection of Cy3-labelled siRNAs. Immunohistochemical studies reveal distinct siRNA uptake and transport mechanisms in HVC->RA and HVC->X projection neurons. Fluorescent in situ hybridizations with zfSIDT2 probes demonstrate a punctate localization of mRNA transcripts in the neuropil, indicating that the mRNA is transported to pre and/or post-synaptic sites for local translation of the putative transport protein. These studies suggest the use of this transport mechanism as a...