Subpopulations of Projection Neurons in the Olfactory Bulb

Abstract

Generation of neuronal diversity is a biological strategy widely used in the brain to process complex information. The olfactory bulb is the first relay station of olfactory information in the vertebrate central nervous system. In the olfactory bulb, axons of the olfactory sensory neurons form synapses with dendrites of projection neurons that transmit the olfactory information to the olfactory cortex. Historically, the olfactory bulb projection neurons have been classified into two populations, mitral cells and tufted cells. The somata of these cells are distinctly segregated within the layers of the olfactory bulb; the mitral cells are located in the mitral cell layer while the tufted cells are found in the external plexiform layer. Although mitral and tufted cells share many morphological, biophysical, and molecular characteristics, they differ in soma size, projection patterns of their dendrites and axons, and odor responses. In addition, tufted cells are further subclassified based on the relative depth of their somata location in the external plexiform layer. Evidence suggests that different types of tufted cells have distinct cellular properties and play different roles in olfactory information processing. Therefore, mitral and different types of tufted cells are considered as starting points for parallel pathways of olfactory information processing in the brain. Moreover, recent studies suggest that mitral cells also consist of heterogeneous subpopulations with different cellular properties despite the fact that the mitral cell layer is a single-cell layer. In this review, we first compare the morphology of projection neurons in the olfactory bulb of different vertebrate species. Next, we explore the similarities and differences among subpopulations of projection neurons in the rodent olfactory bulb. We also discuss the timing of neurogenesis as a factor for the generation of projection neuron heterogeneity in the olfactory bulb. Knowledge about the subpopulations of olfactory bulb projection neurons will contribute to a better understanding of the complex olfactory information processing in higher brain regions.

Keywords: heterogeneity; mitral cell; olfactory bulb; parallel pathways; projection neurons; tufted cell.

FIGURE 1

Basic neural circuit in the rodent olfactory bulb. (A) The olfactory bulb (OB) is formed at the most anterior portion of the telencephalon in the rodent brain. The accessory olfactory bulb (AOB) receiving the pheromonal information from the vomeronasal organ is located at the posterodorsal OB. Mitral cells in the AOB have multiple apical dendrites projecting to multiple glomeruli. The rest of the OB is called the main OB (MOB) and is innervated by olfactory sensory neurons (OSNs). The MOB consists of multiple concentric layers. (B) The OSN axons tangentially run at the surface of the MOB within the olfactory nerve layer (ONL), before entering the glomeruli. Mitral (M) and tufted cell (T) somata are located in the mitral cell layer (MCL) and external plexiform layer (EPL), respectively, and project their primary dendrites to a single glomerulus. In the glomerulus, OSN axons form axodendritic synapses with mitral and tufted cells as well as periglomerular cells (PG). The secondary dendrites of mitral and tufted cells form dendrodendritic synapses with granule cells (G) in the EPL. Somata of periglomerular and granule cells are found in the glomerular layer (GL) and the granule cell layer (GCL), respectively. IPL, internal plexiform layer.

FIGURE 2

Projection neurons in the non-mammalian vertebrate olfactory bulb. (A) Schematic illustrations of projection neurons in the teleost fish olfactory bulb (OB). Mitral (M), and ruffed cells (R) are located in the external cell layer (ECL) (A1). Most teleost fish including carp and goldfish have mitral cells with multiple apical dendrites projecting to multiple glomeruli. However, zebrafish mitral cells have only a single apical dendrite. No secondary dendrites are observed in the mitral cells. A morphological characteristic of ruffed cells is a membranous field surrounding the initial part of the axon. Axonal projection patterns from the zebrafish OB are shown in (A2) (Miyasaka et al., 2014). (B) Schematic illustrations of projection neurons in the amphibian OB. Somata of frog mitral cells (M) are located in the external plexiform layer (EPL) and mitral cell layer (MCL); these two layers are not clearly segregated (B1). Mitral cells have multiple apical dendrites, and some have secondary dendrites that do not project to the glomeruli. Axonal projection pattern from the frog OB are shown in (B2) (Eisthen and Polese, 2010). (C) Schematic illustrations of projection neurons in the reptile OB. OSN axons are not depicted as it has not been clearly shown whether a single OSN of reptiles project unbranched axon to a single glomerulus. Somata of mitral cells (M) are found in the MCL that is clearly segregated from the EPL. A single primary dendrite is formed in lizard mitral cells, while multiple primary dendrites are found in turtle mitral cells (C1). Both lizard and turtle mitral cells have clear secondary dendrites extending within the EPL. Axonal projection pattern from the snake OB are shown in (C2) (Eisthen and Polese, 2010; Ubeda-Banon et al., 2011). pTel and vTel, posterior and ventral telencephalon; Hb, habenula; PT, posterior tuberculum; SN, septal nucleus; lAmg and mAmg, lateral and medial amygdala; AON, anterior olfactory nucleus; OT, olfactory tubercle; LC, lateral cortex; NAOT, nucleus of accessory olfactory tract; vaA, eA, and mA, ventral anterior, external, and medial amygdala; and NS, nucleus sphericus.

FIGURE 3

Subpopulations of projection neurons in rodent main olfactory bulb. (A) Morphological differences of projection neurons in the rodent olfactory bulb (OB). Type I mitral cells (M:I) extend their secondary dendrites in the deepest sublayer of the external plexiform layer (dEPL) while those of type II mitral cells (M:II) project to the intermediate EPL (iEPL). Somata of internal tufted cells (iT) are found in the dEPL, and their secondary dendrites extend in the iEPL. Middle tufted cells are mostly located in the iEPL. Tufted cells located in the superficial EPL (sEPL) or glomerular layer (GL) are classified as external tufted cells (eT). The external tufted cells are further subclassified into cells with secondary dendrites projecting to the sEPL or cells absent of secondary dendrites. The deeper the location of projection neurons cell somata in the OB, the longer the secondary dendrites are. (B) Timings of MOB projection neuron generation in the developing mouse brain. Mitral cells are generated between E9 and E13 followed by the middle (E12–E16) and external (E13–E18) tufted cells.

FIGURE 4

Innervation patterns of olfactory bulb projection neurons in the rodent brain. Mitral cells in the accessory olfactory bulb (AOB) project their axons to the bed nucleus of the accessory olfactory tract (BAOT), the bed nucleus of stria terminalis (BNST), the medial amygdaloid nucleus (MEA), and the posteromedial cortical amygdaloid nucleus (PMCo). Mitral cells (M) in the main olfactory bulb (MOB) innervate the anterior olfactory nucleus (AON), the anterior and posterior piriform cortex (aPC and pPC), the olfactory tubercle (OT), the lateral entorhinal cortex (LEC), the MEA, and the anterior and posterolateral cortical amygdaloid nucleus (ACo and PLCo). However, the axons of tufted cells (mT and eT) project only to the anterior portion of the olfactory cortex including the pars externa of the AON and the anterolateral OT.