TY - JOUR
T1 - A miniature multi-contrast microscope for functional imaging in freely behaving animals
AU - Senarathna, Janaka
AU - Yu, Hang
AU - Deng, Callie
AU - Zou, Alice L.
AU - Issa, John B.
AU - Hadjiabadi, Darian H.
AU - Gil, Stacy
AU - Wang, Qihong
AU - Tyler, Betty M.
AU - Thakor, Nitish V.
AU - Pathak, Arvind P.
N1 - Funding Information:
This research was funded by NIH grants 1R21CA175784-01, 1R01CA196701, P30 NS050274 and a Kavli Neuroscience Distinguished Fellowship (J.S.). The authors wish to thank Mr. J. Burns of Johns Hopkins University for help with fabrication, Mr. B. D. Ward of the Medical College of Wisconsin for assistance with signal processing, Drs. I. Hong and R. Huganir for the transgenic mice, Dr. B. Krishnamachary for assistance with the GFP cell line, Dr. F. Vesuna for assistance with the blood corticosterone assay, and Mr. G. Anderson and Ms. R. Pak for assistance with aspects of microscope design. The mouse schematic in Fig. 3a and Supplementary Fig. 1a was downloaded from https:// openclipart.org/detail/17622/simple-cartoon-mouse-1 and used under the Creative Commons Zero 1.0 Public Domain License.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Neurovascular coupling, cerebrovascular remodeling and hemodynamic changes are critical to brain function, and dysregulated in neuropathologies such as brain tumors. Interrogating these phenomena in freely behaving animals requires a portable microscope with multiple optical contrast mechanisms. Therefore, we developed a miniaturized microscope with: a fluorescence (FL) channel for imaging neural activity (e.g., GCaMP) or fluorescent cancer cells (e.g., 9L-GFP); an intrinsic optical signal (IOS) channel for imaging hemoglobin absorption (i.e., cerebral blood volume); and a laser speckle contrast (LSC) channel for imaging perfusion (i.e., cerebral blood flow). Following extensive validation, we demonstrate the microscope’s capabilities via experiments in unanesthetized murine brains that include: (i) multi-contrast imaging of neurovascular changes following auditory stimulation; (ii) wide-area tonotopic mapping; (iii) EEG-synchronized imaging during anesthesia recovery; and (iv) microvascular connectivity mapping over the life-cycle of a brain tumor. This affordable, flexible, plug-and-play microscope heralds a new era in functional imaging of freely behaving animals.
AB - Neurovascular coupling, cerebrovascular remodeling and hemodynamic changes are critical to brain function, and dysregulated in neuropathologies such as brain tumors. Interrogating these phenomena in freely behaving animals requires a portable microscope with multiple optical contrast mechanisms. Therefore, we developed a miniaturized microscope with: a fluorescence (FL) channel for imaging neural activity (e.g., GCaMP) or fluorescent cancer cells (e.g., 9L-GFP); an intrinsic optical signal (IOS) channel for imaging hemoglobin absorption (i.e., cerebral blood volume); and a laser speckle contrast (LSC) channel for imaging perfusion (i.e., cerebral blood flow). Following extensive validation, we demonstrate the microscope’s capabilities via experiments in unanesthetized murine brains that include: (i) multi-contrast imaging of neurovascular changes following auditory stimulation; (ii) wide-area tonotopic mapping; (iii) EEG-synchronized imaging during anesthesia recovery; and (iv) microvascular connectivity mapping over the life-cycle of a brain tumor. This affordable, flexible, plug-and-play microscope heralds a new era in functional imaging of freely behaving animals.
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U2 - 10.1038/s41467-018-07926-z
DO - 10.1038/s41467-018-07926-z
M3 - Article
C2 - 30626878
AN - SCOPUS:85059797060
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 99
ER -