E. DEPARTMENT OF INTEGRATED GENETICS
E-c. Division of Brain Function - Tatsumi Hirata Group

RESEARCH ACTIVITIES

(1) Theoretical Consideration of Olfactory Axon Targeting with an Activity-Dependent Neural Network Model

Hirokazu Tozaki and Tatsumi Hirata

--Olfactory sensory neurons that express a given odorant receptor target their axons onto a few specific glomeruli in the olfactory bulb. Although the odorant receptor plays an indispensable role in olfactory axon targeting, the mechanisms underlying this guidance are largely unknown. In particular, there is much controversy regarding the involvement of activity-dependent mechanism in the targeting process. In this study, we developed an activity-dependent self-organization model of the glomerular layer in the olfactory bulb and simulated the targeting of olfactory axons onto the layer³⁾. Our model successfully constructed discrete glomeruli that received olfactory axons expressing a common odorant receptor through odorant-evoked neural activities. Furthermore, our model explained the perplexing experimental results that have been reported in olfactory axon targeting. For example, the segregated projection of the axons that express the same odorant receptor transcribed from the different alleles was successfully simulated if the genetically modified allele was assumed to express a smaller amount of the receptor protein. The activity-dependent model even explained the inconsistent effects of disruption of the activity-evoking ion channel on axons expressing different odorant receptors, although some of these results were regarded as evidence for activity-independency of the olfactory targeting. Taken together, the activity-dependent targeting of olfactory axons seems to be a simple probable mechanism that can provide a unified explanation of glomerular formation.

(2) Systematic Screening and Identification of the Antigens Recognized by Monoclonal Antibodies Raised against the Developing Lateral Olfactory Tract

Takahiko Kawasaki, Yoshiko Takagi, Hitoshi Yamatani and Tatsumi Hirata

--During development, olfactory bulb axons navigate the complex microenvironment composed of myriads of molecules in the telencephalon to construct a bundle called the lateral olfactory tract. The axons, themselves, also express thousands of different molecules during the navigation. In this study, we produced and characterized six monoclonal antibodies that label the lateral olfactory tract and the surroundings in a unique pattern²⁾. The labeling profiles suggested that the antigen molecules recognized by each antibody are heterogeneously distributed around the developing lateral olfactory tract. We developed an efficient screening method to identify the antigen molecules by combining expression of a cDNA library in COS-7 cells and the subsequent immunohistochemical staining of the cells. The systematic screening successfully identified the specific cDNA clones for all of the monoclonal antibodies, which highly probably code for the antigen molecules, and therefore unveiled the molecular nature of local components that embrace the developing lateral olfactory tract.

(3) Chronotopic Organization of Olfactory Bulb Axons in the Lateral Olfactory Tract

Hitoshi Yamatani, Yasufumi Sato and Tatsumi Hirata

--The arrangement of axons in a tract can have a specific consequence on the organization of functional neuronal circuits. We found that olfactory bulb axons are chronologically arranged in the lateral olfactory tract⁴⁾. Newly-differentiated projection neurons over the whole olfactory bulb are similarly marked with transient expression of c-kit protein. Their axons are assembled together and project into the ventral superficial part of the tract, displacing the older axons. This special assembly of the axons explains the non-topographical relationships between the olfactory bulb and the lateral olfactory tract axons that have been described in previous studies, and could possibly influence the subsequent selection of the olfactory target areas by these axons.

PUBLICATIONS

Papers
1. Aizawa, H., Sato, Y., Maekawa, M., Fujisawa, H., Hirata, T. and Yuasa, S. (2004). Development of the amygdalohypothalamic projection in the mouse embryonic forebrain. Anat. Embryol. 208, 249-264.
2. Kawasaki, T., Takagi, Y., Yamatani, H. and Hirata, T. (2004). Systematic screening and identification of the antigens recognized by monoclonal antibodies raised against the developing lateral olfactory tract. J. Neurobiol. 62, 330-340.
3. Tozaki, H., Tanaka, S. and Hirata, T. (2004). Theoretical consideration of olfactory axon projection with an activity-dependent neural network model. Mol. Cell. Neurosci. 26, 503-517.
4. Yamatani, H., Sato, Y., Fujisawa, H. and Hirata, T. (2004). Chronotopic organization of olfactory bulb axons in the lateral olfactory tract. J. Comp. Neurol. 475, 247-260.