RT Journal Article
SR Electronic
T1 Functional dissection of neural circuitry using a genetic reporter for fMRI
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.27.424403
DO 10.1101/2020.12.27.424403
A1 Souparno Ghosh
A1 Nan Li
A1 Benjamin B. Bartelle
A1 Tianshu Xie
A1 Jade I. Daher
A1 Urvashi D. Singh
A1 Katherine Xie
A1 Nicholas DiNapoli
A1 Nicholas B. Evans
A1 Kwanghun Chung
A1 Alan Jasanoff
YR 2020
UL http://biorxiv.org/content/early/2020/12/28/2020.12.27.424403.abstract
AB The complex connectivity of the mammalian brain underlies its function, but understanding how interconnected brain regions interact in neural processing remains a formidable challenge. Here we address this problem by introducing a genetic probe that permits selective functional imaging of neural circuit elements defined by their synaptic interrelationships throughout the brain. The probe is an engineered enzyme that transduces cytosolic calcium dynamics of probe-expressing cells into localized hemodynamic responses that can be selectively visualized by functional magnetic resonance imaging. Using a viral vector that undergoes retrograde transport, we apply the probe to characterize a brain-wide network of monosynaptic inputs to the striatum activated in a deep brain stimulation paradigm in rats. The results reveal engagement of surprisingly diverse projection sources and inform an integrated model of striatal function relevant to reward behavior and therapeutic neurostimulation approaches. Our work thus establishes a potent strategy for mechanistic analysis of distributed neural systems.Competing Interest StatementThe authors have declared no competing interest.(BOLD)Blood Oxygen Level-Dependent(CPu)Caudate-Putamen(CCx)Cingulate Cortex(DBS)Deep Brain Stimulation(ECx)Entorhinal Cortex(fMRI)Functional Magnetic Res-onance Imaging(GFP)Green Fluorescent Protein(HSV)Herpes Simplex Virus(iNOS)Induci-ble Nitric Oxide Synthase(ICx)Insular Cortex(LH)Lateral Hypothalamus(L-NAME)L-nitroargi-nine methyl ester(MRI)Magnetic Resonance Imaging(MT)Medial Thalamus(MCx)Motor Cortex(nNOS)Neuronal Nitric Oxide Synthase(NOSTIC)Nitric Oxide Synthase for Targeting Image Contrast(S1)Primary Somatosensory Cortex(SN)Substantia Nigra