Pacemaker Currents in Dopaminergic Neurones of the Mice Olfactory Bulb

In the olfactory bulb (OB) dopaminergic (DA) neurones constitute a fraction of the cells occupying the most external (glomerular) layer (Halász et al.1977). In this region, populated by three types of interneurons, periglomerular (PG) cells, short-axon cells and external tufted (ET) cells (Halász1990) - often collectively referred to as juxtaglomerular cells - an estimated 10% of the neurones in adulthood are positive for tyrosine hydroxylase (TH) (McLean and Shipley1988; Kratskin and Belluzzi2003), the rate limiting enzyme for dopamine synthesis. Dopaminergic neurones in the glomerular layer include PG cells (Gall et al.1987; Kosaka et al.1985) and a fraction of ET cells (Halász1990). Several studies have focused on the role of dopamine in the olfactory bulb, using immunohistochemical (Baker et al.1983; Guthrie et al.1991), behavioral (Doty and Risser1989), and electrophysiological techniques (Nowycky et al.1983; Ennis et al.2001; Davila et al.2003). The more complete description of the functional properties of DA neurons in the OB is probably the paper of Pignatelli (Pignatelli et al.2005), but it was incomplete, as it did not consider the contribution of the inward rectifier currents, a lacuna which is filled in the present work. A property shared by many DA neurons in the CNS is their capacity to generate rhythmic action potentials even in the absence of synaptic inputs (Grace and Onn1989; Hainsworth et al.1991; Yung et al.1991; Feigenspan et al.1998; Neuhoff et al.2002). In this paper we show for the first time that DA cells in the glomerular layer of the olfactory bulb possess a pacemaker activity, and we provide an explanation for the ionic basis of rhythm generation in these cells. There is an additional reason to study the functional properties of DA neurones in the OB other than their role in olfaction. The olfactory bulb is one of the rare regions of the mammalian CNS in which new cells, derived from stem cells in the anterior subventricular zone, are also added in adulthood (Gross2000). In the OB, these cells differentiate in interneurones in the granular and glomerular layers. Among these cells there are DA neurones (Betarbet et al.1996; Baker et al.2001), and this has raised a remarkable interest because, for their accessibility, they could provide a convenient source of autologous DA neurons for transplant therapies in neurodegenerative diseases, like Parkinson’s disease.