Molecular identity of olfactory bulb interneurons: transcriptional codes of periglomerular neuron subtypes

Interneurons in the glomerular layer (GL) of the olfactory bulb represent a diverse set of cells, which can be identified by distinct expression of different neurotransmitters as well as calcium binding proteins. Using genetic based fate mapping, we show here that at least three of these different interneurons subtypes (i.e. dopaminergic, calbindin- and calretinin-expressing) derive from cells that express the homeobox genes Dlx5/6. The transcription factors ER81, Meis2, Pax6 and Sp8 have all been implicated in olfactory bulb interneuron development and each of these can be observed in Dlx5/6-derived periglomerular cells. Conversely, the T-box factors Tbr1 and Tbx21, which mark olfactory bulb projection neurons, are not expressed in the Dlx5/6-derived periglomerular cells. While the interneuron subtypes that are marked by Pax6 and Sp8 have been described, little information exists as to the specific subtypes that express ER81 or Meis2. We show here that ER81 is expressed in dopaminergic cells and in a subset of calretinin-expressing cells in the GL. Meis2 is found in dopaminergic and calbindin-expressing cells as well as in a subpopulation of the calretinin-expressing interneurons of the glomerular layer. These findings suggest that distinct transcriptional codes may underlie the differentiation of specific olfactory bulb interneuron subtypes.