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開啟
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  • 20250327-1
  • 演講或講座
  • 生物醫學科學研究所
  • 地點

    生醫所地下室B1B演講廳

  • 演講人姓名

    陳怡文博士 (Univ. of Geneva)

  • 活動狀態

    確定

  • 活動網址
High-throughput synaptic connectivity mapping of neocortical microcircuits in vivo using holographic light

2025-03-27 14:00 - 15:00

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Synaptic connectivity between neocortical neurons lays out the basis of many brain functions including sensory processing and behaviors and may be impaired in brain dysfunctions. Whereas electrophysiological approaches using multiple patch microelectrodes have been well established for probing synaptic connections, they are limited in throughput and usually carried out in vitro, hindering the applications of long-range circuitry and longitudinal investigation. In this study, we introduce a novel framework for in vivo connectivity mapping that combines two-photon holographic optogenetic stimulation, whole-cell recording, and a compressive sensing strategy. We demonstrate the feasibility of this approach by investigating the local synaptic connectivity at layer 2/3 of anesthetized mouse visual cortex. Holographic stimulation of single cell enables rapid sequential probing of connectivity of up to 100 cells in ~5 minutes. By identifying tens of synaptic pairs and characterizing their connection strength, kinetics, and spatial distribution, this method showcases its potential to significantly advance circuit reconstruction in large neuronal networks with lower invasiveness compared to multi-patch approaches. Further, we demonstrate that by combining simultaneous holographic multi-cell stimulation with the compressed sensing algorithm, a more efficient sampling of the presynaptic population can be achieved. Under the conditions of sparse connectivity and linear summation of synaptic inputs, the algorithm allowed recovery of most connections with up to three-fold reduction in the number of required measurements, highlighting the potential for improved throughput in connectivity mapping. Overall, our results demonstrate efficient investigation of local neocortical neuronal network in vivo by using holographic light, and the methodologies could potentially be applied in other areas of the nervous system.

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