Physiological properties and adult neurogenesis of dopaminergic neurons in the mouse olfactory bulb

The olfactory bulb (OB) of mammals contains a large population of dopaminergic (DA) interneurons within the glomerular layer (GL) which have been shown to modulate several aspects of olfactory information processing. To study the functional properties of DA neurons, we used a transgenic mouse strain harbouring an eGFP reporter construct under the promoter of tyrosine hydroxylase, allowing the identification of dopaminergic neurons (TH-GFP cells) in living preparations. The most prominent feature of these cells was the autorhythmicity, that we show is supported by the interplay of the a persistent Na+ current and of a T-type Ca2+ current. In these cells we have identified six main voltage-dependent conductances, that we have completely kinetically characterized, developing a numerical model of TH-GFP cells, capable of reproducing accurately the properties of living cells. A significant fraction of the bulbar DA interneurons is added in adulthood. In the OB, DA neurons are restricted to the GL, but in TH-GFP transgenic mice we also detected the presence of GFP+ cells in the mitral and external plexiform layers. We show that these are adult-generated neurons committed to become DA but not yet entirely differentiated. Accordingly, TH-GFP+ cells outside the GL exhibit functional properties (appearance of pacemaker currents, synaptic connection with the olfactory nerve, intracellular chloride concentration, and other) marking a gradient of maturity toward the dopaminergic phenotype along the mitral-glomerular axis. Finally, we propose that the establishment of a synaptic contact with the olfactory nerve is the key event allowing these cells to complete their differentiation toward the DA phenotype and to reach their final destination.