The role of neurogenesis in olfaction-dependent behaviors.

Newly born neurons continuously migrate into the main and accessory olfactory bulbs and modulate the output of projection neurons. Despite some contradictory results, it is becoming clear that these newly born neurons play an important role in the response to some odorant cues. In this minireview, we discuss the recent findings surrounding the functional significance of adult neurogenesis in olfaction-dependent behaviors

Real-time imaging of bHLH transcription factors reveals their dynamic control in the multipotency and fate choice of neural stem cells

The basic-helix-loop-helix (bHLH) transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate the fate choice of neurons, astrocytes, and oligodendrocytes, respectively; however, these factors are coexpressed in self-renewing multipotent neural stem cells (NSCs) even before cell fate determination. This fact raises the possibility that these fate determination factors are differentially expressed between self-renewing and differentiating NSCs with unique expression dynamics. Real-time imaging analysis utilizing fluorescent proteins is a powerful strategy for monitoring expression dynamics. Fusion with fluorescent reporters makes it possible to analyze the dynamic behavior of specific proteins in living cells. However, it is technically challenging to conduct long-term imaging of proteins, particularly those with low expression levels, because a high-sensitivity and low-noise imaging system is required, and very often bleaching of fluorescent proteins and cell toxicity by prolonged laser exposure are problematic. Furthermore, to analyze the functional roles of the dynamic expression of cellular proteins, it is essential to image reporter fusion proteins that are expressed at comparable levels to their endogenous expression. In this review, we introduce our recent reports about the dynamic control of bHLH transcription factors in multipotency and fate choice of NSCs, focusing on real-time imaging of fluorescent reporters fused with bHLH transcription factors. Our imaging results indicate that bHLH transcription factors are expressed in an oscillatory manner by NSCs, and that one of them becomes dominant during fate choice. We propose that the multipotent state of NSCs correlates with the oscillatory expression of several bHLH transcription factors, whereas the differentiated state correlates with the sustained expression of a single bHLH transcription factor

Thurston's pullback map on the augmented Teichm\"uller space and applications

Let $f$ be a postcritically finite branched self-cover of a 2-dimensional topological sphere. Such a map induces an analytic self-map $\sigma_f$ of a finite-dimensional Teichm\"uller space. We prove that this map extends continuously to the augmented Teichm\"uller space and give an explicit construction for this extension. This allows us to characterize the dynamics of Thurston's pullback map near invariant strata of the boundary of the augmented Teichm\"uller space. The resulting classification of invariant boundary strata is used to prove a conjecture by Pilgrim and to infer further properties of Thurston's pullback map. Our approach also yields new proofs of Thurston's theorem and Pilgrim's Canonical Obstruction theorem.Comment: revised version, 28 page

Nonperturbative Model Of Liouville Gravity

We obtain nonperturbative results in the framework of continuous Liouville theory. In particular, we express the specific heat ${\cal Z}$ of pure gravity in terms of an expansion of integrals on moduli spaces of punctured Riemann spheres. The integrands are written in terms of the Liouville action. We show that ${\cal Z}$ satisfies the Painlev\'e I.Comment: 11 pages, LaTex fil

Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb -- the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells -- are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures

Genetic Methods to Identify and Manipulate Newly Born Neurons in the Adult Brain

Although mammalian neurogenesis is mostly completed by the perinatal period, new neurons are continuously generated in the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. Since the discovery of adult neurogenesis, many extensive studies have been performed on various aspects of adult neurogenesis, including proliferation and fate-specification of adult neural stem cells, and the migration, maturation and synaptic integration of newly born neurons. Furthermore, recent research has shed light on the intensive contribution of adult neurogenesis to olfactory-related and hippocampus-mediated brain functions. The field of adult neurogenesis progressed tremendously thanks to technical advances that facilitate the identification and selective manipulation of newly born neurons among billions of pre-existing neurons in the adult central nervous system. In this review, we introduce recent advances in the methodologies for visualizing newly generated neurons and manipulating neurogenesis in the adult brain. Particularly, the application of site-specific recombinases and Tet inducible system in combination with transgenic or gene targeting strategy is discussed in further detail

可動性超分子キラリティーの識別:有機触媒を用いたアシル化による分子変換

京都大学0048新制・課程博士博士(薬科学)甲第19660号薬科博第48号新制||薬科||6(附属図書館)32696京都大学大学院薬学研究科薬科学専攻(主査)教授 川端 猛夫, 教授 高須 清誠, 教授 竹本 佳司学位規則第4条第1項該当Doctor of Pharmaceutical SciencesKyoto UniversityDFA