TY - JOUR
T1 - Functional and multiscale 3D structural investigation of brain tissue through correlative in vivo physiology, synchrotron microtomography and volume electron microscopy
AU - Bosch, Carles
AU - Ackels, Tobias
AU - Pacureanu, Alexandra
AU - Zhang, Yuxin
AU - Peddie, Christopher J.
AU - Berning, Manuel
AU - Rzepka, Norman
AU - Zdora, Marie Christine
AU - Whiteley, Isabell
AU - Storm, Malte
AU - Bonnin, Anne
AU - Rau, Christoph
AU - Margrie, Troy
AU - Collinson, Lucy
AU - Schaefer, Andreas T.
N1 - Funding Information:
The authors are grateful to the advanced light microscopy, biological research, electron microscopy and scientific computing science technology platforms of the Francis Crick Institute. We thank Ede Rancz, John Bogovic, Kevin Briggman and Sina Tootoonian for discussion, Marta Majkut and Alexander Rack for support and imaging experiments at ID19, and Peter Cloetens and Pierre Paleo for discussion and support with data analysis and synchrotron imaging. This research was funded in whole, or in part, by the Wellcome Trust (FC001153 and 110174/Z/15/Z to A.T.S.; FC001999 to L.M.C.; 090843/F/09/Z to T.W.M.). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was carried out with the support of Diamond Light Source, beamline I13-2 (proposal 20274), the TOMCAT beamline of the Swiss Light Source at the Paul Scherrer Institut (proposal 20190417) and the ID16A and ID19 beamlines of the European Synchrotron Radiation Facility (proposal ih-ls-3253). This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001153 to A.T.S.; FC001999 to L.M.C.), the UK Medical Research Council (FC001153 to A.T.S., FC001999 to L.M.C.), and the Wellcome Trust (FC001153 to A.T.S., FC001999 to L.M.C.). It was also supported by the UK Medical Research Council (MC_UP_1202/5 to A.T.S.), by the Gatsby Charitable Foundation (GAT3361 to T.W.M.) and by a DFG postdoctoral fellowship to T.A. A.P. acknowledges funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (852455).
Funding Information:
The authors are grateful to the advanced light microscopy, biological research, electron microscopy and scientific computing science technology platforms of the Francis Crick Institute. We thank Ede Rancz, John Bogovic, Kevin Briggman and Sina Tootoonian for discussion, Marta Majkut and Alexander Rack for support and imaging experiments at ID19, and Peter Cloetens and Pierre Paleo for discussion and support with data analysis and synchrotron imaging. This research was funded in whole, or in part, by the Wellcome Trust (FC001153 and 110174/Z/15/Z to A.T.S.; FC001999 to L.M.C.; 090843/F/09/Z to T.W.M.). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was carried out with the support of Diamond Light Source, beamline I13-2 (proposal 20274), the TOMCAT beamline of the Swiss Light Source at the Paul Scherrer Institut (proposal 20190417) and the ID16A and ID19 beamlines of the European Synchrotron Radiation Facility (proposal ih-ls-3253). This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001153 to A.T.S.; FC001999 to L.M.C.), the UK Medical Research Council (FC001153 to A.T.S., FC001999 to L.M.C.), and the Wellcome Trust (FC001153 to A.T.S., FC001999 to L.M.C.). It was also supported by the UK Medical Research Council (MC_UP_1202/5 to A.T.S.), by the Gatsby Charitable Foundation (GAT3361 to T.W.M.) and by a DFG postdoctoral fellowship to T.A. A.P. acknowledges funding from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme (852455).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Understanding the function of biological tissues requires a coordinated study of physiology and structure, exploring volumes that contain complete functional units at a detail that resolves the relevant features. Here, we introduce an approach to address this challenge: Mouse brain tissue sections containing a region where function was recorded using in vivo 2-photon calcium imaging were stained, dehydrated, resin-embedded and imaged with synchrotron X-ray computed tomography with propagation-based phase contrast (SXRT). SXRT provided context at subcellular detail, and could be followed by targeted acquisition of multiple volumes using serial block-face electron microscopy (SBEM). In the olfactory bulb, combining SXRT and SBEM enabled disambiguation of in vivo-assigned regions of interest. In the hippocampus, we found that superficial pyramidal neurons in CA1a displayed a larger density of spine apparati than deeper ones. Altogether, this approach can enable a functional and structural investigation of subcellular features in the context of cells and tissues.
AB - Understanding the function of biological tissues requires a coordinated study of physiology and structure, exploring volumes that contain complete functional units at a detail that resolves the relevant features. Here, we introduce an approach to address this challenge: Mouse brain tissue sections containing a region where function was recorded using in vivo 2-photon calcium imaging were stained, dehydrated, resin-embedded and imaged with synchrotron X-ray computed tomography with propagation-based phase contrast (SXRT). SXRT provided context at subcellular detail, and could be followed by targeted acquisition of multiple volumes using serial block-face electron microscopy (SBEM). In the olfactory bulb, combining SXRT and SBEM enabled disambiguation of in vivo-assigned regions of interest. In the hippocampus, we found that superficial pyramidal neurons in CA1a displayed a larger density of spine apparati than deeper ones. Altogether, this approach can enable a functional and structural investigation of subcellular features in the context of cells and tissues.
UR - https://www.scopus.com/pages/publications/85130696877
U2 - 10.1038/s41467-022-30199-6
DO - 10.1038/s41467-022-30199-6
M3 - Article
C2 - 35614048
AN - SCOPUS:85130696877
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2923
ER -