Differential expression of axon-sorting molecules in mouse olfactory sensory neurons.
- 1Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 113-0033, Japan.
- 2Cell Signal Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Japan.
- 3Center for Information and Neural Networks, National Institute of Information and Communications Technology, Suita, Japan.
- 4PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Japan.
In the mouse olfactory system, the axons of olfactory sensory neurons that express the same type of odorant receptor (OR) converge to a specific set of glomeruli in the olfactory bulb (OB). It is widely accepted that expressed OR molecules instruct glomerular segregation by regulating the expression of axon-sorting molecules. Although the relationship between the expression of axon-sorting molecules and OR types has been analyzed in detail, those between the expressions of axon-sorting molecules remain to be elucidated. Here we collected the expression profiles of four axon-sorting molecules from a large number of glomeruli in the OB. These molecules demonstrated position-independent mosaic expressions, but their patterns were not identical in the OB. Comparing their expressions identified positive and negative correlations between several pairs of genes even though they showed various expressions. Furthermore, the principal component analysis revealed that the factor loadings in the principal component 1, which explain the largest amount of variation, were most likely to reflect the degree of the cyclic nucleotide-gated (CNG) channel dependence on the expression of axon-sorting molecules. Thus, neural activity generated through the CNG channel is a major component in the generation of a wide variety of expressions of axon-sorting molecules in glomerular segregation.
KEYWORDS: axon guidance; gene expression; neural activity; neural circuit formation; olfactory system
- PMID: 27207328; DOI: 10.1111/ejn.13282
The mouse olfactory system
Fig 1A: The odorant receptor (OR) gene family constitutes the largest group of G protein-coupled receptor genes comprised of >1,000 genes. An individual olfactory sensory neuron (OSN) expresses only one functional OR, and OSNs expressing the same type of OR converge their axons to form the glomerulus in the olfactory bulb (OB). A single odorant activates multiple ORs with different intensities. Thus, odor information generated by the binding of odorants with ORs in the olfactory epithelium (OE) is converted into two-dimensional activation pattern of glomeruli in the OB.
Fig 1B: Expressed OR molecules regulate the expression of axon-sorting molecules (e.g., Kirrel2, OLPC, BIG-2), and thereby generate combinatorial expressions of axon-sorting molecules at OSN axon termini (top). Enlarged photos are also shown (bottom). Immunostaining of an OB section revealed that all of these molecules showed position-independent mosaic expressions, but their patterns were not identical.
Model depicting activity-dependent neural circuit formation in the mouse olfactory system
Fig 2: ORs produce cyclic adenosine monophosphate (cAMP) through the activation of the receptor-coupled G proteins and adenylyl cyclase type III (AC III). Increase in the cAMP levels open up the cyclic nucleotide-gated (CNG) channel, leading to generate OSN action potentials. We found that neural activity generated through the CNG channel is a major component in the generation of a wide variety of expressions of axon-sorting molecules. The combinatorial expressions of the axon-sorting molecules provide axons with distinct identities for OR-dependent circuit formation.