Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks.
The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with μPET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach.
Michael
M
Michaelides
Sarah Ann R
SA
Anderson
Mala
M
Ananth
Denis
D
Smirnov
Panayotis K
PK
Thanos
John F
JF
Neumaier
Gene-Jack
GJ
Wang
Nora D
ND
Volkow
Yasmin L
YL
Hurd
D000200:Action Potentials; D000818:Animals; D001921:Brain / Q000033:anatomy & histology*; D001931:Brain Mapping / Q000379:methods*; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D015198:Designer Drugs; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D008297:Male; D009043:Motor Activity; D009415:Nerve Net / Q000033:anatomy & histology* / Q000737:chemistry / Q000000981:diagnostic imaging; D009434:Neural Pathways; D059906:Neuroimaging / Q000379:methods*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009714:Nucleus Accumbens / Q000737:chemistry / Q000166:cytology* / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013003:Somatosensory Cortex / Q000033:anatomy & histology; D013997:Time Factors; D014738:Vibrissae / Q000294:innervation; D014851:Wakefulness
D015198:Designer Drugs; D004745:Enkephalins; D005462:Fluorine Radioisotopes; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C029992:proenkephalin; D019788:Fluorodeoxyglucose F18; C033660:preproenkephalin; D003024:Clozapine; C079149:clozapine N-oxide