title: Mapping brain metabolic connectivity in awake rats with μPET and optogenetic stimulation.
abstract: Positron emission tomography (PET) with [(18)F]2-fluoro-2-deoxy-D-glucose was used to measure changes in regional brain glucose metabolism (BGluM) in response to optogenetic stimulation (using the excitatory channelrhodopsin-2) of the nucleus accumbens (NAc) in awake rats. We demonstrated not only increases in BGluM that correlated with c-Fos expression in the region of stimulation, but also BGluM increases in the ipsilateral striatum, periaqueductal gray, and somatosensory cortex, and in contralateral amygdala, ventral pallidum, globus pallidus, and hippocampus, as well as decreases in BGluM in regions of the default mode network (retrosplenial cortex and cingulate gyrus) and secondary motor cortex. Additional exploration of c-Fos expression in regions found to be activated by PET results found corroborating evidence, with increased c-Fos expression in the ipsilateral somatosensory cortex, contralateral amygdala and globus pallidus, and bilateral periaqueductal gray. These findings are consistent with optogenetic excitation of the area of stimulation (NAc), as well as with stimulatory and inhibitory effects on downstream regions. They also confirm the utility of PET imaging to monitor connectivity in the awake rodent brain.
authors.affiliation: Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA.
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.forename: Lisa
authors.initials: L
authors.lastname: Robison
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
authors.forename: Ronald
authors.initials: R
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Michaelides
authors.forename: Mary-Kay
authors.initials: MK
authors.lastname: Lobo
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D001931:Brain Mapping / Q000379:methods / Q000523:psychology*; D000075402:Channelrhodopsins; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D062308:Optogenetics / Q000379:methods / Q000523:psychology*; D049268:Positron-Emission Tomography / Q000379:methods*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014851:Wakefulness
chemical_list: D000075402:Channelrhodopsins; D016760:Proto-Oncogene Proteins c-fos; D019788:Fluorodeoxyglucose F18; D005947:Glucose