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Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits

View ORCID ProfileD Barson, View ORCID ProfileAS Hamodi, View ORCID ProfileX Shen, View ORCID ProfileG Lur, View ORCID ProfileRT Constable, View ORCID ProfileJA Cardin, View ORCID ProfileMC Crair, View ORCID ProfileMJ Higley
doi: https://doi.org/10.1101/468348
D Barson
1Department of Neuroscience, Yale School of Medicine
2Interdepartmental Neuroscience Program, Yale School of Medicine
3MD/PhD Program, Yale School of Medicine
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AS Hamodi
1Department of Neuroscience, Yale School of Medicine
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X Shen
4Department of Radiology and Biomedical Imaging, Yale School of Medicine
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G Lur
5Department of Neurobiology and Behavior, University of California, Irvine
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RT Constable
2Interdepartmental Neuroscience Program, Yale School of Medicine
4Department of Radiology and Biomedical Imaging, Yale School of Medicine
6Department of Neurosurgery, Yale School of Medicine
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JA Cardin
1Department of Neuroscience, Yale School of Medicine
7Kavli Institute for Neuroscience, Yale School of Medicine
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MC Crair
1Department of Neuroscience, Yale School of Medicine
7Kavli Institute for Neuroscience, Yale School of Medicine
8Department of Ophthalmology and Visual Science, Yale School of Medicine
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MJ Higley
1Department of Neuroscience, Yale School of Medicine
7Kavli Institute for Neuroscience, Yale School of Medicine
9Program in Cellular Neuroscience, Neurodegeneration and Repair
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Abstract

Spontaneous and sensory-evoked activity propagates across spatial scales in the mammalian cortex but technical challenges have generally precluded establishing conceptual links between the function of local circuits of neurons and brain-wide network dynamics. To solve this problem, we developed a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake, behaving mice. Our method employs an orthogonal axis design whereby the mesoscopic objective is oriented downward directly above the brain and the two-photon objective is oriented horizontally, with imaging performed through a glass right angle microprism implanted in the skull. In support of this method, we introduce a suite of analysis tools for relating the activity of individual cells to distal cortical areas, as well as a viral method for robust and widespread gene delivery in the juvenile mouse brain. We use these methods to characterize the diversity of associations of individual, genetically-defined neurons with cortex-wide network motifs.

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Posted November 11, 2018.
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Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits
D Barson, AS Hamodi, X Shen, G Lur, RT Constable, JA Cardin, MC Crair, MJ Higley
bioRxiv 468348; doi: https://doi.org/10.1101/468348
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Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits
D Barson, AS Hamodi, X Shen, G Lur, RT Constable, JA Cardin, MC Crair, MJ Higley
bioRxiv 468348; doi: https://doi.org/10.1101/468348

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