Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks
Michael Michaelides, … , Nora D. Volkow, Yasmin L. Hurd
Michael Michaelides, … , Nora D. Volkow, Yasmin L. Hurd
Published November 15, 2013
Citation Information: J Clin Invest. 2013;123(12):5342-5350. https://doi.org/10.1172/JCI72117.
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Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

Abstract

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.

Authors

Michael Michaelides, Sarah Ann R. Anderson, Mala Ananth, Denis Smirnov, Panayotis K. Thanos, John F. Neumaier, Gene-Jack Wang, Nora D. Volkow, Yasmin L. Hurd

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Figure 4

Cell-type–specific, time-dependent control of local and long range signaling is detected using DREAMM in anesthetized rats.

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Cell-type–specific, time-dependent control of local and long range signa...
Time-dependent DREAMM responses after (A) Pdyn- and (B) Penk-expressing MSN inhibition (P = 0.05; relative increase [red] and decrease [blue] in FDG uptake) in sagittal planes and corresponding images from the Paxinos rat brain atlas. Individual subject voxel values in the VTA showing that Pdyn-MSN inhibition significantly increases FDG uptake at 1 minute (P = 0.002) and decreases FDG uptake at 30 minutes (P = 0.03) (C) in comparison with vehicle condition, while Penk-MSN inhibition does not (D). CB, cerebellum; IC, inferior colliculus; AOP, anterior olfactory nucleus; VLL, ventral nucleus of lateral lemniscus; PN, pontine nuclei; RN, reticular nuclei; VC, visual cortex; RS, retrosplenial cortex; CPu, caudate putamen; LPO, lateral preoptic area; LH, lateral hypothalamus; TH, thalamus; BN, brainstem nuclei. *P < 0.05; **P < 0.01.