Developmental regulation of olfactory circuit formation in mice

Abstract

In mammals, odorants induce various behavioral responses that are critical to the survival of the individual and species. Binding signals of odorants to odorant receptors (ORs) expressed in the olfactory epithelia are converted to an odor map, a pattern of activated glomeruli, in the olfactory bulb (OB). This topographic map is used to identify odorants for memory-based learned decisions. In the embryo, a coarse olfactory map is generated in the OB by a combination of dorsal-ventral and anterior-posterior targeting of olfactory sensory neurons (OSNs), using specific sets of axon-guidance molecules. During the process of OSN projection, odor signals are sorted into distinct odor qualities in separate functional domains in the OB. Odor information is then conveyed by the projection neurons, mitral/tufted cells, to various regions in the olfactory cortex, particularly to the amygdala for innate olfactory decisions. Although the basic architecture of hard-wired circuits is generated by a genetic program, innate olfactory responses are modified by neonatal odor experience in an activity-dependent manner. Stimulus-driven OR activity promotes post-synaptic events and dendrite selection in the responding glomeruli making them larger. As a result, enhanced odor inputs in neonates establish imprinted olfactory memory that induces attractive responses in adults, even when the odor quality is innately aversive. In this paper, I will provide an overview of the recent progress made in the olfactory circuit formation in mice. K E Y W O R D Samygdala, axon guidance, decision making, imprinting, olfactory circuit

Subpopulations of Projection Neurons in the Olfactory Bulb

“…Figure 1 shows the structure of the rodent OB as an anatomical model for reference. Although we do not go deeper into detail in this review, there are many excellent reviews summarizing the cell types, synapses, and neuronal circuits found in the MOB ( Shepherd et al, 2004 ; Wachowiak and Shipley, 2006 ; Figueres-Onate et al, 2014 ; Imai, 2014 ; Nagayama et al, 2014 ; Sakano, 2020 ). Briefly, the OSN axons run tangentially through the olfactory nerve layer (ONL) at the surface of the OB before entering the glomerular layer (GL) ( Klenoff and Greer, 1998 ; Rodriguez-Gil et al, 2015 ).…”

Trans-Axonal Signaling in Neural Circuit Wiring

“…In the mouse olfactory system, about one thousand types of olfactory sensory neurons (OSNs) convey odor information perceived in the olfactory epithelium (OE) to the olfactory bulb (OB). Each OSN expresses a single type of G protein-coupled odorant receptor (OR), and same-type OSNs expressing the same OR extend axons that converge onto common individual target sites called glomeruli in the olfactory bulb [ 100 ]. As the organization of glomeruli does not correlate with the position of the OSNs in the OE, convergence of olfactory axons onto specific glomeruli along the antero-posterior axis is ensured by pre-target axon sorting ( Figure 2 B).…”

“…In the mouse olfactory system, for instance, olfactory axons are segregated along the dorso-ventral axis and maintain their relative position from their exit from the OE to their entry of the OB. Axons from the dorsomedial zone of the OE project to the dorsal part of the OB first and are followed by axons from the ventrolateral zone that project to the ventral OB [ 100 , 118 , 119 ]. Interestingly, Sema3F and its receptor Neuropilin-2 (Nrp2) are expressed in a complementary graded manner along the dorso-ventral axis in OSNs.…”

“…cAMP then activates transcription of Nrp1, which is expressed in a complementary manner to its ligand, Sema3A, in the olfactory nerve. Repulsive signaling between Nrp1- and Sema3A-expressing axons sorts axons as they extend to the olfactory bulb (OB) [ 99 , 100 , 101 , 102 , 103 , 104 ]. ( CI ) Repulsion between nasal and rostral retinal axons at the superior colliculus (SC) contributes to topographic mapping.…”

Emerging evidence for cell‐autonomous axon guidance

“…Some reports further suggest that topographic organization occurs before the growth cone reaches the target tissue (Imai et al, 2009;Sakano, 2020). In olfactory sensory neurons (OSNs), complementary expression of the axon-guidance receptor Neuropilin-1 and its repulsive ligand Semaphorin-3A leads to pre-target axon segregation and topography based on relative protein levels (Imai et al, 2009;Sakano, 2020). Gain-and loss of function of one of those molecules specifically in OSNs leads to abnormalities in pre-target axon sorting by shifting axons from the Neuropilin-1 high bundle to the Neuropilin-1 low bundle, or vice versa.…”