Adult Born Olfactory Bulb Dopaminergic Interneurons: Molecular Determinants and Experience-Dependent Plasticity

Abstract

The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications.

Keywords: COUP-TFI; adult neurogenesis; dopaminergic neurons; juxtaglomerular neurons; odor deprivation; odor enrichment; olfactory bulb; tyrosine hydroxylase.

Figure 1

Olfactory bulb dopaminergic interneurons. New image from previously published experiments (Bovetti et al., ; Bonzano et al., 2014). (A) Photomicrograph showing a coronal section of the olfactory bulb (OB) in a 2-month-old wild-type mouse. DA cells immunopositive for TH (green) are mostly confined within the OB glomerular layer (GL). (B) BrdU-positive adult born DA cell (arrow) in a representative confocal image of the OB GL double-stained for BrdU (red) and TH (green) in a mouse that received BrdU at 2 months of age and analyzed 42 days after. B′ shows higher magnification and re-slicing of the BrdU/TH double positive cell. (C) Multiple labeling of the OB GL in a 2-month-old TH-GFP transgenic mouse line (Sawamoto et al., 2001). GFP (green) is expressed under the control of TH promoter; TH-immunopositive cells are shown in blue and COUP-TFI immunopositive nuclei in red. C1 shows higher magnification of a cell that is triple labeled for GFP/TH/COUP-TFI (white arrow) and a cell that is double labeled for GFP and COUP-TFI (white arrowhead). C2 shows higher magnification of a cell that is double labeled for GFP and TH (yellow arrow). C3 shows a cell that is triple labeled for GFP/TH/COUP-TFI (white arrow) and a cell that is GFP-positive only (yellow arrowhead). (D) Venn diagram showing the overlap of the labeling for TH-GFP, TH and COUP-TFI immunoreactivity based on our previously published data (Bovetti et al., 2013). A fraction of TH-GFP positive cells is negative for both TH and COUP-TFI. As previously reported these cells are likely immature DA neurons not expressing yet TH protein (Pignatelli et al., 2009). There is a high overlap between TH-GFP/TH/COUP-TFI labeling indicating that COUP-TFI expression is tightly associated with the DA phenotype. Scale bar in A = 500 μm. Scale bar in B and C = 50 μm. Scale bar in inset B′ = 10 μm. Scale bar in inset C1 = 10 μm and refers to C2 and C3. ONL, olfactory nerve layer; GL, glomerular layer; EPL, external plexiform layer; MCL, mitral cell layer; IPL, internal plexiform layer; GcL, granule cell layer; RMS, rostral migratory stream of the OB.