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The Journal of Neuroscience, June 7, 2006, 26(23):6330-6336; doi:10.1523/JNEUROSCI.0626-06.2006
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Cellular/Molecular
Blood Oxygenation Level-Dependent Visualization of Synaptic Relay Stations of Sensory Pathways along the Neuroaxis in Response to Graded Sensory Stimulation of a Limb
Johan Lilja,1
Toshiki Endo,1
Christoph Hofstetter,1
Eric Westman,2
Jeremy Young,4
Lars Olson,1 and
Christian Spenger3
1Department of Neuroscience, 2Neurotec, and 3Clintec, Karolinska Institutet, S-171 76 Stockholm, Sweden, and 4 AstraZeneca R&D, 151 85 Södertälje, Sweden
Correspondence should be addressed to Christian Spenger, Clintec, Experimental MR Research Center, Karolinska University Hospital, S-171 76 Stockholm, Sweden. Email: Christian.spenger{at}ki.se
Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to test at which levels of the neuroaxis signals are elicited when different modalities of sensory information from the limbs ascend to cortex cerebri. We applied graded electric stimuli to the rat hindlimbs and used echo-planar imaging to monitor activity changes in the lumbar spinal cord and medulla oblongata, where primary afferents of painful and nonpainful sensation synapse, respectively. BOLD signals were detected in ipsilateral lumbar spinal cord gray matter using sufficiently strong stimuli. Using stimuli well below the threshold needed for signals to be elicited in the spinal cord, we found BOLD responses in dorsal medulla oblongata. The distribution of these signals is compatible with the neuroanatomy of the respective synaptic relay stations of the corresponding sensory pathways. Hence, the sensory pathways conducting painful and nonpainful information were successfully distinguished. The fMRI signals in the spinal cord were markedly decreased by morphine, and these effects were counteracted by naloxone. We conclude that fMRI can be used as a reliable and valid method to monitor neuronal activity in the rat spinal cord and medulla oblongata in response to sensory stimuli. Previously, we also documented BOLD signals from thalamus and cortex. Thus, BOLD responses can be elicited at all principal synaptic relay stations along the neuroaxis from lumbar spinal cord to sensory cortex. Rat spinal cord fMRI should become a useful tool in experimental spinal cord injury and pain research.
Key words: fMRI; rat; spinal cord; somatosensory; dorsal horn; medulla; pain; morphine; BOLD; EPI
Received Feb. 13, 2006;
revised May 2, 2006;
accepted May 2, 2006.
Correspondence should be addressed to Christian Spenger, Clintec, Experimental MR Research Center, Karolinska University Hospital, S-171 76 Stockholm, Sweden. Email: Christian.spenger{at}ki.se
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