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The Journal of Neuroscience, July 23, 2008, 28(30):7637-7647; doi:10.1523/JNEUROSCI.1488-08.2008

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Behavioral/Systems/Cognitive
Mapping Prefrontal Circuits In Vivo with Manganese-Enhanced Magnetic Resonance Imaging in Monkeys

Janine M. Simmons,¹ Ziad S. Saad,² Martin J. Lizak,³ Michael Ortiz,¹ Alan P. Koretsky,³ and Barry J. Richmond¹

¹Laboratory of Neuropsychology and ²Scientific and Statistical Computing Core, National Institute of Mental Health, and ³NMR Imaging Research Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-4415

Correspondence should be addressed to Barry J. Richmond, Building 49, Room 1B80, National Institute of Mental Health, Bethesda, MD 20892-4415. Email: bjr{at}ln.nimh.nih.gov

Manganese-enhanced magnetic resonance imaging (MEMRI) provides a powerful tool to study multisynaptic circuits in vivo and thereby to link information about neural structure and function within individual subjects. Making the best use of MEMRI in monkeys requires minimizing manganese-associated neurotoxicity, maintaining sensitivity to manganese-dependent signal changes and mapping transport throughout the brain without a priori anatomical hypotheses. Here, we performed intracortical injections of isotonic MnCl₂, comparisons of preinjection and postinjection scans, and voxelwise statistical mapping. Isotonic MnCl₂ did not cause cell death at the injection site, damage to downstream targets of manganese transport, behavioral deficits, or changes in neuronal responsiveness. We detected and mapped manganese transport throughout cortical–subcortical circuits by using voxelwise statistical comparisons of at least 10 preinjection and two postinjection scans. We were able to differentiate between focal and diffuse projection fields and to distinguish between the topography of striatal projections from orbitofrontal and anterior cingulate cortex in a single animal. This MEMRI approach provides a basis for combining circuit-based anatomical analyses with simultaneous single-unit recordings and/or functional magnetic resonance imaging in individual monkeys. Such studies will enhance our interpretations of functional data and our understanding of how neuronal activity is transformed as it propagates through a circuit.

Key words: orbitofrontal cortex; anterior cingulate cortex; striatum; neuroanatomy; tract tracing; nonhuman primate

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Received Feb. 28, 2008; revised May 29, 2008; accepted June 11, 2008.

Correspondence should be addressed to Barry J. Richmond, Building 49, Room 1B80, National Institute of Mental Health, Bethesda, MD 20892-4415. Email: bjr{at}ln.nimh.nih.gov

This article has been cited by other articles:

				S. Bouret and B. J. Richmond Relation of Locus Coeruleus Neurons in Monkeys to Pavlovian and Operant Behaviors J Neurophysiol, February 1, 2009; 101(2): 898 - 911. [Abstract] [Full Text] [PDF]

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