Topographically Distinct Projection Patterns of Early-Generated and Late-Generated Projection Neurons in the Mouse Olfactory Bulb

Abstract

In the mouse brain, olfactory information is transmitted to the olfactory cortex via olfactory bulb (OB) projection neurons known as mitral and tufted cells. Although mitral and tufted cells share many cellular characteristics, these cell types are distinct in their somata location and in their axonal and dendritic projection patterns. Moreover, mitral cells consist of heterogeneous subpopulations. We have previously shown that mitral cells generated at different embryonic days differentially localize within the mitral cell layer and extend their lateral dendrites to different sublayers of the external plexiform layer. Here, we examined the axonal projection patterns from the subpopulations of OB projection neurons that are determined by the timing of neurogenesis (neuronal birthdate) to understand the developmental origin of the diversity in olfactory pathways. We separately labeled early-and late-generated OB projection neurons using in utero electroporation performed at embryonic day 11 and 12, respectively, and quantitatively analyzed their axonal projection patterns in the whole mouse brain using highresolution 3D imaging. In this study, we demonstrate that the axonal projection of late-generated OB projection neurons is restricted to the anterior portion of the olfactory cortex while those of the early-generated OB projection neurons innervate the entire olfactory cortex. Our results suggest that the late-generated mitral cells do not extend their axons to the posterior regions of the olfactory cortex. Therefore, the mitral cells having different birthdates differ, not only in cell body location and dendritic projections within the OB, but also in their axonal projection pattern to the olfactory cortex. 3 Significance Statement The olfactory bulb contains long-range projection neurons with distinct connectivity to higher order brain regions. Here, we examined how the birthdate of the olfactory bulb projection neurons correlates to the generation of differential connectivity patterns. We used in utero electroporation and high-resolution 3D imaging of the whole mouse brain, and determined the topographically distinct axonal projection patterns of early-and late-generated olfactory bulb projection neurons. Our results show that the timing of neurogenesis is a determining factor for the innervation of olfactory bulb projection neurons and indicate that mitral cells having different birthdates are the origins of distinct olfactory information pathways. Our study provides novel insights into the formation of neuronal circuits processing multiple aspects of olfactory information.

Pituitary hormones are specifically expressed in trigeminal sensory neurons and contribute to pain responses in the trigeminal system

“…Nodose-jugular ganglion complex has a specialized role in regulation of several vital visceral organs such as heart, lung, trachea, esophagus, and intestine 16 . Comparison of NG/JG sensory neuronal transcriptomic profiles to DRG revealed only several NG/JG-selective DEGs using outlined selection criteria (see “Materials and Methods”) (Table 2 ).…”

“…Additionally, DRG and TG neurons differ in their translational potential for mTOR-related genes and AMP-activated protein kinase 15 . With regards to NG sensory neurons, they possess much different expression profiles compared to sensory neurons from JG and DRG 16 .…”

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

“…While the olfactory second-order neurons (MCs/TCs) share a multitude of features, they differ in two distinct ways, anatomically; (1) somata location within the OB, and (2) neurite projection patterns. MCs project their axons to most structures within the olfactory cortex (OC), whereas TC axons are more localized to targets including the anterior olfactory nucleus, olfactory tubercle, and anterior piriform cortex [68][69][70][71] . When drawing comparisons to other sensory systems, this information leads us to speculate that the differences in axonal projection patterns of MCs and TCs may also be a component of the olfactory system impacted by the pathophysiological nature of COI.…”

Excitable axonal domains adapt to sensory deprivation in the olfactory system

“…While precise firing patterns are generated in the OB, MC axons must carry these signals out of the OB to the piriform cortex and other brain regions via the highly myelinated LOT (Nagayama et al, 2010;Imamura et al, 2020;Chon et al, 2020;Walz et al, 2006;Schwob and Price, 1984).…”

“…In the olfactory bulb (OB), the firing rates and synchronized firing patterns of mitral (MC) and tufted cells encode vital olfactory information such as odor identity and odor salience (whether an odor deserves attention) (Friedrich et al, 2004;Doucette et al, 2011;Lepousez and Lledo, 2013;Gire et al, 2013). The precise signals generated in the mouse OB must faithfully travel several millimeters along myelinated axonal tracts before reaching other brain regions such as the piriform cortex (Nagayama et al, 2010;Imamura et al, 2020;Chon et al, 2020;Walz et al, 2006;Schwob and Price, 1984). Downstream neurons in the piriform cortex are very sensitive to synchronized input, often failing to fire if the latency of incoming action potentials (AP)s is greater than 10ms (Franks and Isaacson, 2006;Luna and Schoppa, 2008;Bolding and Franks, 2018).…”