Role of neuronal activity and kinesin on tract tracing by manganese-enhanced MRI (MEMRI)
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 Mn^(2+) uptake, transport and trans-synaptic tracing. By measuring electrical response to light before and after injection of Mn^(2+) into the eye, we determine the dose of Mn^(2+) 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 Mn^(2+) 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 Mn^(2+) in the optic tract. This work provides a molecular and physiological framework for interpreting data acquired by MEMRI of circuitry in the brain.
Additional Information© 2007 Elsevier Inc. Received 2 February 2007; revised 19 April 2007; accepted 20 April 2007. Available online 13 May 2007. We thank Scott Fraser at Caltech and Larry Goldstein at UCSD for their support, and Carol Readhead, Tim Hiltner and Jean Edens for technical assistance. We gratefully acknowledge the Moore Foundation for awarding a Moore Distinguished Scholar to E.L.B. which funded her to work at Caltech while on sabbatical from Brown. The project was also funded in part by NIH NIGMS GM47368, NINDS NS046810 and P20 RR018757 (E.L.B.), NCRR-BIRN (R.E.J.) and the Pew Fellow Program and The American Parkinson Disease Association (T.L.F).
Accepted Version - nihms-29710.pdf