シンポジウム
20 感覚・運動回路の神経活動依存的な回路発達
20 Activity-dependent development of sensory and motor circuits
座長：今井 猛（九州大学大学院医学研究院）・Feller Marla B.（Department of Molecular and Cell Biology, University of California, Berkeley） |
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| 2022年7月2日 9:00～9:24 沖縄コンベンションセンター 会議場B1 第3会場
3S03m-01
側方抑制シグナルに基づくニューロン内シナプス競合
Lateral inhibition signals for intraneuronal synaptic competitions
*今井 猛(1)
1. 九州大学
*Takeshi Imai Imai(1)
1. Kyushu University
Keyword: synapse elimination, dendrite remodeling, olfactory bulb, spontaneous activity
In developing brains, neurons initially form excessive connections and then remodel them to form precise neuronal circuitry. Inter- and intra-neuronal synaptic competitions have been postulated, but their nature has remained elusive. In the mouse olfactory bulb, mitral cells initially extend multiple dendrites to multiple glomeruli, but developmentally they prune all but single primary dendrites. It has remained unknown how they establish just one dendritic connection. Here we show that genetically silencing neuronal activity in mitral cells, but not neurotransmission from olfactory sensory neurons, precludes developmental dendrite pruning. Glutamatergic spontaneous activity generated within the olfactory bulb is essential. We also find that NMDARs and RhoA mediate the competitive dendrite pruning. FRET imaging shows that glutamatergic inputs via NMDARs locally suppress RhoA, but globally activate it within a mitral cell to selectively prune weaker dendrites. Thus, activity-dependent long-range lateral inhibition via Rho GTPases establishes just one primary dendrite in a mitral cell. | | 2022年7月2日 9:24～9:48 沖縄コンベンションセンター 会議場B1 第3会場
3S03m-02
新生仔期バレル皮質における第4層神経細胞の樹状突起精緻化
Dendritic refinement of layer 4 neurons in the neonatal barrel cortex
*岩里 琢治(1)
1. 国立遺伝学研究所
*Takuji Iwasato(1)
1. National Institute of Genetics
Keyword: activity-dependent development, somatosensory cortex, mouse
Precise neuronal connectivity in the mammalian cortex is established through refinement during postnatal stages. To understand mechanisms underlying developmental cortical circuit reorganization, dendritic refinement of spiny stellate neurons in the mouse somatosensory cortex layer 4 (barrel neurons) is an ideal model. Barrel neurons located at the barrel edge have basal dendrites asymmetrically expanded primarily within a single barrel. This orientation bias of barrel neuron dendrites, which underlies a precise one-to-one functional relationship between whiskers and barrels, is established essentially during the 1st postnatal week in an NMDA receptor (NMDAR)-mediated activity-dependent manner. Towards understanding the mechanism of barrel neuron dendritic refinement, we have used two-photon microscope in vivo imaging (Mizuno et al., Neuron 2014). Three-day long longitudinal imaging of neonatal barrel cortex starting at postnatal day (P)3 revealed that barrel neurons acquire their strong dendritic orientation bias through differential dynamics of dendritic trees (Nakazawa et al., Nature Commun. 2018). In a more recent work, we are focusing on the possible involvement of the organelle in dendritic refinement. We found that Golgi apparatus (GA), which was localized in the apical dendrite at P1, translocated to the soma between P3 and P5 in barrel neurons. At P5, the GA showed biased distribution toward the barrel center within the soma and was even partially deployed into the longest barrel center-oriented basal dendrite. These laterally polarized distributions of the GA in barrel neurons mostly disappeared by P15, by when the dendritic refinement is essentially completed. Genetic manipulation that disrupts the polarized GA distribution reduced the orientation bias of basal dendrites toward the barrel center. It also affects the response specificity of barrel neurons to the stimulation of the primary whisker. Knockout of NR1, the essential NMDAR subunit, attenuated the GA polarity. Thus, the lateral redistribution of the GA is a key step of NMDAR-mediated dendritic refinement of barrel neurons. Our study reveals the developmental dynamics of cortical neuron dendrites and an important role of organelle dynamics for dendritic refinement in the neonatal cortex. | | 2022年7月2日 9:48～10:12 沖縄コンベンションセンター 会議場B1 第3会場
3S03m-03
網膜の方向選択性の軸形成はホメオボックス遺伝子Vax2に制御される
Retinal direction selectivity specified by homeobox gene Vax2
*米原 圭祐(1,2,3)、松本 彰弘(3)、山本 悠(3)、Allice Lind(3)
1. 国立遺伝学研究所、2. 総合研究大学院大学遺伝学専攻、3. オーフス大学医学部ダンドライト研究所
*Keisuke Yonehara(1,2,3), Akihiro Matsumoto(3), Haruka Yamamoto(3), Allice Nyborg Rosenkrans Lind(3)
1. National Institute of Genetics, Mishima, Japan, 2. Dept of Genetics, Grad Univ for Adv Studies (SOKENDAI), Japan, 3. DANDRITE, Dept of Biomed, Aarhus Univ, Denmark
Keyword: Retinal direction selectivity, Homeobox gene Vax2, Two-photon imaging, Asymmetric circuit development
Spatially asymmetric neuronal connections are critical components of neuronal processing. How asymmetric neuronal connections are specified precisely along body axes, however, remains unknown. Here we show that Ventral anterior homeobox 2 (Vax2) transcription factor, which shows a high ventronasal to low dorsotemporal gradient expression in the developing retina, is necessary for establishing direction selectivity in the mouse retina. Electrophysiological and two-photon imaging analyses show that Vax2 knockout retinas have reduced direction selectivity in ventronasal direction. This is accompanied by the transition from asymmetric to symmetric inhibitory inputs from starburst amacrine cells to DS cell types with a genetic identity of ventral or nasal motion-preferring DS cells. Centrifugal direction selectivity of starburst cells was unaffected. Developmental cell-type transcriptome analysis identified Vax2-regulated genes in the starburst cells. We are under investigation of the effect of Vax2 on the retinal wave of spontaneous activity during neonatal development. Thus, our work demonstrates that asymmetric neuronal connections for retinal direction selectivity are established along the retinal axes specified by the Vax2 gradient. | | 2022年7月2日 10:12～10:36 沖縄コンベンションセンター 会議場B1 第3会場
3S03m-04
A role for retinal waves in the estabishment of direction selectivity
*Marla Feller(1), Alex Tiriac(1), Karina Bistrong(1), Miah Pitcher(1), Joshua Tworig(1)
1. University of California, Berkeley
Keyword: two-photon calcium imaging, activity-dependent development, amacrine cells
The development of neural circuits is profoundly impacted by both spontaneous and sensory experience. This is perhaps most well studied in the visual system, where disruption of early spontaneous activity called retinal waves prior to eye opening and visual deprivation after eye opening leads to alterations in the response properties and connectivity in several visual centers in the brain. We address this question in the retina, which comprises multiple circuits that encode different features of the visual scene, culminating in over 40 different types of retinal ganglion cells. Direction-selective ganglion cells respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite, or null, direction. Moreover, the preferred directions of direction selective ganglion cells cluster along four directions that align along two optic flow axes, causing variation of the relative orientation of preferred directions along the retinal surface.
I will provide recent progress in the lab that demonstrates that direction selectivity maps are largely present at eye opening and develop normally in the absence of visual experience. We also found that mice lacking the beta2 subunit of neuronal nicotinic acetylcholine receptors (β2-nAChR-KO), which exhibit drastically reduced cholinergic retinal waves in the first postnatal week, lack direction selectivity to horizontal motion while selectivity to vertical motion remains. We tested several possible mechanisms that could explain the loss of horizontal direction selectivity in β2-nAChR-KO mice (wave propagation bias, FRMD7 expression, starburst amacrine cell morphology) but all were found to be intact when compared to WT mice. This work establishes a role for retinal waves in the development of asymmetric circuitry that mediates retinal direction selectivity via an unknown mechanism. | | 2022年7月2日 10:36～11:00 沖縄コンベンションセンター 会議場B1 第3会場
3S03m-05
ショウジョウバエ運動回路の発生に必須な自発活動出現の分子細胞メカニズム
Molecular and cellular mechanisms underlying the emergence of spontaneous patterned activity crucial for motor development in Drosophila
曽 祥孫澤(1)、駒野目 ゆう子(1)、風間 北斗(2)、*能瀬 聡直(1,3)
1. 東京大学大学院新領域創成科学研究科、2. 理研CBS、3. 東京大学大学院理学系研究科
XiangSunZe Zeng(1), Yuko Komanome(1), Hokto Kazama(2), *Akinao Nose(1,3)
1. Grad Sch of Frontier Sciences, Univ of Tokyo, Chiba, Japan, 2. CBS, RIKEN, Saitama, Japan, 3. Grad Sch Science, Univ of Tokyo, Tokyo, Japan
Keyword: motor development, Drosophila, spontaneous activity, sensory feedback
Spontaneous neural activity is widely observed in developing circuitry throughout the nervous system. Whilst a wealth of research has demonstrated crucial roles played by spontaneous activity in sensory development, much less is known about the roles of spontaneous activity in developing motor circuits. A unique feature during motor development is the generation of premature movements by spontaneous neural activity. For instance, a human fetus makes a constellation of involuntary movements such as wiggling and kicking in mother’s womb. It has long been hypothesized that such precocious movements and ensuing proprioceptive feedback represent a trial-and-error process that allows the developing central circuits to gauge the effectiveness of movements and adaptively shape themselves in an experience-dependent manner. However, how spontaneous activity emerges in developing motor circuits and contributes to the formation of motor patterns remain unclear.
We address these issues by using as a model the development of peristaltic locomotion in Drosophila embryos. We found that a pioneering circuit composed of M and A27h interneurons autonomously generates nasent spontaneous activity via IP3-mediated calcium release from internal stores and thereby induces premature movement of the body. When spontaneous activity or gap-junctional transmission in the circuit were specifically blocked, the CPG circuits failed to form. Furthermore, proprioceptive feedback of premature movements was in turn required for the development of gap-junctional connections in the M/A27h circuit. Therefore, the pioneer circuit senses the feedback of its own outputs and enables development of the entire locomotor network. These findings not only provide experimental evidence for a crucial role played by spontaneous activity and proprioceptive feedback in the development of motor circuits, but also show how a pioneer circuit enables activity-dependent development of a locomotor network (Zeng et al., 2021). We are currently trying to identify GPCRs acting upstream of the IP3-signaling to understand how the spontaneous activity is generated in the first place. By conducting an RNAi-based screen combined with behavioral analysis and calcium imaging, we identified several candidate GPCRs which are required in the M/A27h circuit for generation of spontaneous activities and proper development of locomotion. Further characterization of the GPCRs will be presented at the meeting. | | | |
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