一般口演（Oral）

Oral Axon/Dendrite Growth and Circuit Formation-1 一般口演軸索と樹状突起の伸長と回路形成-1

7月27日（土）8:45～9:00　第9会場（朱鷺メッセ　3F　306+307） 3O-09m1-1 A quantitative in vivo time-lapse imaging screen reveals the critical molecular mechanisms of major dendrite branch formation Li-Foong Yoong（Yoong Li-Foong）¹，Hui-Keem Lim（Lim Hui-Keem）²，Heidi Tran（Tran Heidi）¹，Simone Lackner（Lackner Simone）¹，Zhihao Zheng（Zheng Zhihao）³，Pengyu Hong（Hong Pengyu）³，Adrian W Moore（Moore Adrian W）¹ ¹RIKEN Center for Brain Science ²University of Science Malaysia, International Program Associate, Penang, Malaysia ³Brandeis University, Department of Computer Science, Boston, MA, USA Dendrite arbor branching patterns determine the number, distribution and integration of neuron inputs; neuron firing properties. A mature dendrite arbor pattern is the compound outcome of a series of branching events. Major primary branches created early in dendrite outgrowth process delineate the arbor into its distinct main subtrees and subsequently determine its targeting into correct innervation fields. Nevertheless, while extensive analyses have revealed processes that regulate terminal dendrite and spine patterning, mechanisms constructing the critical major primary branches remain fundamentally unknown. Here, we developed a robust in vivo time-lapse imaging system coupled with machine learning-based quantification utilizing Drosophila melanogaster sensory neuron in the pupal stage. Through this we identified and tracked the critical early dendrite outgrowth events and linked these to the later establishment of mature dendrite arbor pattern. We found that during early outgrowth stage, dendritic growth cone expanded lammelipodial which undergoes programmed splitting to generate major branches. Genetic screen utilizing in vivo time-lapse imaging identified Myosin6 as a principal player in this dendritic growth cone remodeling process. Molecular-level tracking of cytoskeletal remodeling further revealed the transient local upregulation of anterograde-directed microtubule nucleation events in the growth cone. Myosin6 drives retrograde extension of set of specialized actin filament arrays that guides microtubule invasion and subdivide growth cone into multiple branches. Furthermore, Myo6 and the transcription factor Knot tune arbor complexity by amplifying this program. As primary branches delineate functional compartments; this tunable mechanism is key to define and diversify dendrite compartmentalization.		7月27日（土）9:00～9:15　第9会場（朱鷺メッセ　3F　306+307） 3O-09m1-2 走化性によるトポグラフィック地図の軸索配線 Naoki Honda（本田直樹）京都大学　生命科学研究科 Neural circuits are wired by chemotactic migration of growth cones guided by extracellular guidance cue gradients. How growth cone chemotaxis builds the macroscopic structure of the neural circuit is a fundamental question in neuroscience. I addressed this issue on the ordered axonal projections called topographic maps. In the retina and tectum, the erythropoietin-producing hepatocellular (Eph) receptors and their ligands, the ephrins, are expressed in gradients. According to Sperry's chemoaffinity theory, gradients in both the source and target areas enable projecting axons to recognize their proper terminals, but how axons chemotactically decode their destinations is largely unknown. To identify the chemotactic mechanism of topographic mapping, I developed a mathematical model of intracellular signaling in the growth cone that focuses on the growth cone's unique chemotactic property of being attracted or repelled by the same guidance cues in different biological situations. The model presented mechanism by which the retinal growth cone reaches the correct terminal zone in the tectum through alternating chemotactic response between attraction and repulsion around a preferred concentration. The model also provided a unified understanding of the contrasting relationships between receptor expression levels and preferred ligand concentrations in EphA/ephrinA- and EphB/ephrinB-encoded topographic mappings. Thus, this study redefines the chemoaffinity theory, highlighting the importance of the growth cone's unique ability to alternate between attraction and repulsion.

7月27日（土）9:15～9:30　第9会場（朱鷺メッセ　3F　306+307） 3O-09m1-3 小脳ルガロ細胞の帯状構造特異的な入力様式と介在ニューロンへの抑制性支配様式 Taisuke Miyazaki（宮崎太輔）¹，Miwako Yamasaki（山崎美和子）¹，Kenji F Tanaka（田中謙二）²，Masahiko Watanabe（渡辺雅彦）¹ ¹北海道大学医学研究院解剖発生学教室 ²慶応大学医学部精神神経科学教室 Lugaro cells (LCs) are cerebellar interneurons located just beneath the Purkinje cell layer, receive inhibitory axon collaterals from Purkinje cells, and project axons to inhibitory interneurons in the molecular layer and Golgi cells. However, LCs are still the most enigmatic cerebellar interneuron, and their input-output organization and its relationship with cerebellar compartments are unclear. In the present study, we serendipitously produced a transgenic mouse line where a half of yellow cameleon (YC)(+) cells in the cerebellar cortex were LCs, and YC(+) LCs constituted one-third of the total LC populations. Using this mouse model, we analyzed neuroanatomical properties of YC(+) LCs. Neurochemically, two-thirds of YC(+) LCs were dually GABAergic/glycinergic, with the rest being purely GABAergic. Just beneath the PC layer, they extended a sheet of somatodendritic meshwork interconnected with neighboring LCs by adherens junctions, and received various inputs from climbing fibers, mossy fibers, granule cell axons, recurrent PC axons, Golgi cell axons, LC axons, and serotonergic fibers. Intriguingly, somatodendritic elements of individual LCs preferentially extended within a given cerebellar compartment defined by aldolase C expression. In turn, YC(+) LCs projected a dense lattice of ascending and transverse axons to the molecular layer, and innervated molecular layer interneurons (basket and stellate cells) and Golgi cells, but not PCs. Of note, ascending axons profusely innervated individual targets within a cerebellar compartment, while transverse axons ran across several compartments and sparsely innervated targets. This unique circuit configuration highlights that LCs integrate various excitatory, inhibitory, and modulatory inputs coming to the belonging cerebellar compartment and that, as an interneuron-selective interneuron, LCs can effectively disinhibit cerebellar cortical activities in a compartment-dependent manner through inhibition of inhibitory interneurons selectively targeting PCs and granule cells.		7月27日（土）9:30～9:45　第9会場（朱鷺メッセ　3F　306+307） 3O-09m1-4 胎仔期小脳におけるプルキンエ細胞区画の発達、神経細胞誕生日特異的標識による解析 Khoa Tran-Anh（トランアンコア）¹，Tatsumi Hirata（平田たつみ）²，Viet Nguyen-Minh（Nguyen-Minh Tuan Viet）¹，Izumi Sugihara（杉原泉）^1,3 ¹東京医科歯科大学、システム神経生理学分野 ²国立遺伝学研究所 ³東京医科歯科大学、脳機能統合センター The cerebellum is involved in many functions, including motor control, cognition, and language, by means of transverse lobules and longitudinal compartments. Thus, a better understanding of the compartmentalization is a necessity to study the diverse functions of the cerebellum. Such cerebellar longitudinal compartments contain Purkinje cells (PCs) which are born on a particular date (embryonic day 10.5, 11.5 or 12.5) and share similar molecular expression profiles and afferent and efferent connections. PC compartmentalization is thought to be appropriately organized during development but this process in embryonic stage remains mostly ambiguous. To address the question, we tracked the development of all PC clusters, which are demarcated by the differences of molecular expressions and cell-free gaps, from embryonic day 14.5 (E14.5) to E17.5 in the entire cerebellum. Experiments were done by immunostaining serial sections of the embryonic mouse cerebellum for several marker molecules of embryonic cerebellar compartments (EphA4, Pcdh10, FoxP2 and Corl2). We used wild type mouse embryos as well as mouse embryos that were obtained by mating G2A strain male (neuronal birthday tagging system) with Ai9 strain female and received tamoxifen at E10.5, E11.5 or E12.5 were used. We observed 9 distinct PC clusters at E14.5, which then divided separately into some 40 clusters at E17.5. Importantly, each cluster was composed of PCs that had specific birth date(s). PCs that shared the same birthday constituted particular clusters and the spatial pattern of such clusters were preserved during development. Moreover, some clusters, which were derived from the same origin and have the same birthday, eventually, changed their molecular expression to become indistinguishable. The present study was the first to clarify the transformation of all PC clusters in the embryonic stage from E14.5 to E17.5. These results suggest that fates of PC compartments are determined in the early embryonic stage.