Title:
Developmental Regulation of Neural Circuit Formation in the Mouse Olfactory System

Hitoshi Sakano
Department of Biophysics and Biochemistry, Graduate School of Science
University of Tokyo

Abstract:
G-protein coupled receptors (GPCRs) including odorant receptors (ORs) are known to possess two different conformations, active and inactive, and generate unique levels of basal activities by interchanging the two conformations in the absence of agonists. In the mouse olfactory bulb ( OB ), olfactory sensory neurons (OSNs) expressing the same OR species converge their axons to a specific site forming a glomerular structure. Here, we report that receptor-instructed axonal projection is regulated by the basal activity of GPCRs. We generated and analyzed transgenic mice expressing basal-activity mutants of b 2-adrenergic receptor ( β2-AR). β2-AR is a member of GPCRs with the highest homology to ORs and is capable of replacing some functions of ORs. We found that b 2-AR mutants that altered the basal activity, but not the agonist-induced activity, changed transcription levels of axon guidance molecules. The present study gives us a definite answer to a long-standing question in the mammalian olfactory research, i.e., what defines the OR identity and how it is converted to a molecular code on the extending OSN axons. It is the basal activity of ORs that represents the neuronal identity of OSNs by regulating expression levels of axon-guidance molecules.

References:
Mori, K. and Sakano, H.: How is the olfactory map formed and interpreted in the mammalian brain?Ann. Rev. Neurosci . 34 , 465-497 (2011).