Activity-dependent local protection and lateral inhibition control synaptic competition in developing mitral cells in mice

Fujimoto, Satoshi; Leiwe, Marcus N.; Aihara, Shuhei; Sakaguchi, Richi; Muroyama, Yuko; Kobayakawa, Reiko; Kobayakawa, Ko; Saito, Tetsuichiro; Imai, Takeshi

doi:10.1016/j.devcel.2023.05.004

Cited by 20 publications

(10 citation statements)

References 81 publications

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“…Our finding superficially resembles the formation of exuberant connections followed by synapse elimination in the vertebrate neuromuscular junction, climbing fiber–Purkinje cell connections, and retinal ganglion cell–lateral geniculate connections discussed above, as well as activity-dependent refinement of ORN axons and mitral cell dendrites in glomeruli of the mammalian olfactory bulb 86,87 . A fundamental difference is the time scale.…”

Section: Discussionsupporting

confidence: 76%

Molecular and Cellular Mechanisms of Teneurin Signaling in Synaptic Partner Matching

Xu,

Li,

Lyu

et al. 2024

Preprint

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SUMMARYIn developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionally conserved teneurins were the first identified transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurin’s functions is unclear. Here, we usein situproximity labeling to obtain the intracellular interactome of teneurin (Ten-m) in theDrosophilabrain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.HIGHLIGHTSIn situspatial proteomics reveal the first intracellular interactome of teneurinsTen-m signals via a RhoGAP and Rac1 GTPase to regulate synaptic partner matchingSingle-axon analyses reveal a stabilization-upon-contact model for partner matchingTen-m signaling promotes F-actin in axon branches contacting partner dendrites

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Section: Discussionsupporting

confidence: 76%

Molecular and Cellular Mechanisms of Teneurin Signaling in Synaptic Partner Matching

Xu,

Li,

Lyu

et al. 2024

Preprint

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“…Possibly, action potential backpropagation might contribute to stabilize the larger dendrite. NMDA receptor signaling has been shown in developing mouse olfactory bulb mitral cells to stabilize one of the primary dendrites by suppressing RhoA, and concurrently this "winner" dendrite triggers the pruning of the other dendrites (Fujimoto et al, 2023) Further, parvalbumin interneurons richly express tropomyosin receptor kinase B (TrkB) (Gorba and Wahle 1999). The dendritogenetic effect of axonal TrkB receptor activation and axonal signaling endosomes has been demonstrated for cortical neurons (Moya-Alvarado et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Axons of cortical basket cells originating from dendrites develop higher local complexity than axons emerging from basket cell somata

Gonda,

Riedel,

Reiner

et al. 2023

Preprint

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Neuronal differentiation is regulated by neuronal activity. Here, we analyzed dendritic and axonal growth of Basket cells and non-Basket cells using sparse transfection of channelrhodopsin-YFP and repetitive optogenetic stimulation in slice cultures of rat visual cortex. Neocortical interneurons often display axon-carrying dendrites (AcDs). We found that the AcDs of Basket cells and non-Basket cells were on average their most complex dendrite. Further, the AcD configuration had an influence on Basket cell axonal development. Axons originating from an AcD formed denser arborizations with more terminal endings within the dendritic field of the parent cell. Intriguingly, this occurred already in unstimulated Basket cells, and complexity was not increased further by optogenetic stimulation. However, optogenetic stimulation exerted a growth-promoting effect on axons emerging from Basket cell somata. The axons of non-Basket cells neither responded to the AcD configuration nor to the optogenetic stimulation. The results suggest that the formation of locally dense Basket cell plexuses is regulated by spontaneous activity. Moreover, in the AcD configuration, the AcD and the axon it carries mutually support each others growth.TeaserTextbooks usually draw cortical neurons with axons emerging from the cell body. Axons emerging from dendrites have been considered a caprice of nature until recent work demonstrated that axon-carrying dendrites are neither a rare nor a random phenomenon. Rather, this morphological configuration awards specific functional properties. Here, we discovered a morphogenetic role of the AcD configuration in developing Basket neurons which deliver axo-somatic inhibition to pyramidal neurons. Driven by spontaneous activity, AcD and the axon mutually promote each others growth such that the axon rapidly forms a denser presynaptic terminal field. Basket cells with axons from the cell body achieve the same complexity with technical assistance via an optogenetic stimulation. This way, a dendritic origin accelerates Basket cell axonal development.

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Section: Main Textmentioning

confidence: 99%

“…In the developing central nervous system, correlated spontaneous activity begins as synchronized patterns in localized or extensive areas (3)(4)(5)(6)(7)(8). Synchronized patterns then transition to desynchronized states as seen in the cortex, cerebellum, and olfactory bulb (3,7,8). The maturation of excitatory and inhibitory synapses, synapse elimination, local network dynamics, and inputs from other regions have been suggested as candidate mechanisms that cause synchronized spontaneous activity and mediate the transition from the synchronization to desynchronization.…”

Section: Main Textmentioning

confidence: 99%

Developmental oligodendrocytes regulate brain function through the mediation of synchronized spontaneous activity

Masumura,

Goda,

Sekiguchi

et al. 2024

Preprint

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Immature animals have the ability to interact with their environment, indicating that complex neural circuits are formed through mechanisms of self-organization. Correlated spontaneous activity among neurons suggests a universal principle behind the self-organization of complex neural circuits1,2, though the underlying mechanisms and functional roles in the central nervous system remain unclear. Here, we show that oligodendrocyte-dependent synchronized spontaneous activity during the critical period is indispensable for neural circuit refinement and brain functionalization. We found that oligodendrocyte deletion during specific time window disrupts Purkinje cell activity synchrony and synapse elimination in the mouse cerebellum. We further demonstrated that synchronized spontaneous activity is a prerequisite for synapse elimination. Behavioral analyses linked these developmental disruptions to adult cerebellar function, manifesting as anxiety-like behavior, reduced social interaction, and compromised motor coordination in adult mice. This association indicates the significance of following the appropriate developmental trajectory to ensure the integrity of brain function, suggesting that oligodendrocytes during development are vital organizers of brain functionalization. Our findings highlight the crucial role of oligodendrocytes in orchestrating synapse elimination and optimizing brain function through the mediation of synchronized activity during specific developmental stages.

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Activity-dependent local protection and lateral inhibition control synaptic competition in developing mitral cells in mice

Cited by 20 publications

References 81 publications

Molecular and Cellular Mechanisms of Teneurin Signaling in Synaptic Partner Matching

Molecular and Cellular Mechanisms of Teneurin Signaling in Synaptic Partner Matching

Axons of cortical basket cells originating from dendrites develop higher local complexity than axons emerging from basket cell somata

Developmental oligodendrocytes regulate brain function through the mediation of synchronized spontaneous activity

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