title: Role of neuronal activity and kinesin on tract tracing by manganese-enhanced MRI (MEMRI).
abstract: MEMRI offers the exciting possibility of tracing neuronal circuits in living animals by MRI. Here we use the power of mouse genetics and the simplicity of the visual system to test rigorously the parameters affecting Mn2+ uptake, transport and trans-synaptic tracing. By measuring electrical response to light before and after injection of Mn2+ into the eye, we determine the dose of Mn2+ with the least toxicity that can still be imaged by MR at 11.7 T. Using mice with genetic retinal blindness, we discover that electrical activity is not necessary for uptake and transport of Mn2+ in the optic nerve but is required for trans-synaptic transmission of this tracer to distal neurons in this pathway. Finally, using a kinesin light chain 1 knockout mouse, we find that conventional kinesin is a participant but not essential to neuronal transport of Mn2+ in the optic tract. This work provides a molecular and physiological framework for interpreting data acquired by MEMRI of circuitry in the brain.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA. Elaine_Bearer@Brown.edu
authors.forename: Elaine L
authors.initials: EL
authors.lastname: Bearer
authors.forename: Tomás Luis
authors.initials: TL
authors.lastname: Falzone
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Octavian
authors.initials: O
authors.lastname: Biris
authors.forename: Arkady
authors.initials: A
authors.lastname: Rasin
authors.forename: Russell E
authors.initials: RE
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001766:Blindness / Q000503:physiopathology; D002452:Cell Count; D004594:Electrophysiology; D005074:Evoked Potentials, Visual / Q000502:physiology; D005838:Genotype; D016547:Kinesins / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D010786:Photoreceptor Cells / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000502:physiology; D013569:Synapses / Q000502:physiology; D014795:Visual Pathways / Q000166:cytology / Q000502:physiology
chemical_list: D008869:Microtubule-Associated Proteins; D008345:Manganese; D016547:Kinesins