[HTML][HTML] Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

M Michaelides, SAR Anderson… - The Journal of …, 2013 - Am Soc Clin Investig
The Journal of clinical investigation, 2013Am Soc Clin Investig
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 d esigner r eceptor e xclusively a ctivated by d esigner d
rug (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 DRE ADD-a ssisted m etabolic m …
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.
The Journal of Clinical Investigation