John E. Downey1,2, Piotr Walczak3,4,
Suresh E. Joel1,2, Assaf A. Gilad3,4, Michael T.
McMahon1,2, Heechul Kim3,4, James J. Pekar1,2,
Galit Pelled, 2,5
1F.M. Kirby Research Center for
Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United
States; 2The Russell H. Morgan Department of Radiology and
Radiological Sciences , Johns Hopkins University School of Medicine,
Baltimore, MD, United States; 3The Russell H. Morgan Department of
Radiology and Radiological Sciences, Johns Hopkins University School of
Medicine, Baltimore, MD, United States; 4Cellular Imaging Section,
Vascular Biology Program, Institute for Cell Engineering , Johns Hopkins
University School of Medicine, Baltimore, MD, United States; 5F.M.
Kirby Research Center for Functional Brain Imaging, Kennedy Krieger
Institute , Baltimore, MD, United
States
Recent
developments in optical-genetic (optogenetics) approaches enable immediate
manipulations of neuronal firing rate by using light-induced activation of
light sensitive pumps. We have engineered the excitatory neurons in rat
somatosensory cortex to express halorhodopsin (light-sensitive chloride pump)
using direct neuronal infection with lentivirus. Thus, in the presence of
light, the chloride pumps open and trigger neuronal hyperpolarization i.e.
decreases in neuronal firing rate. Consistent with electrophysiology results,
light induced activation of halorhodopsin during forepaw stimulation,
decreased the amplitude and the extent of fMRI responses. These results
introduce an exciting and novel approach to study neuronal behavior in vivo.