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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Technical Advance

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 6

Unilateral inhibition of spatially overlapping Pdyn- and Penk-expressing neurons in NAcSh of freely moving rats leads to changes in distinct neural circuits.

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Unilateral inhibition of spatially overlapping Pdyn- and Penk-expressing...
(A) Pdyn-MSN inhibition (n = 6) increased FDG uptake in specific corticolimbic regions including the Ent, DI, CG, and MEA as well as VP/HDB as visualized in coronal, sagittal and horizontal planes and (B) as plotted as percentage change in signal response *P < 0.05; **P < 0.01. (C) Penk-MSN inhibition (n = 5) led to profound activation of the DI, medial orbital prefrontal cortices (mOR and mPFC), HP circuit, amygdala, VP, and decreased activity of SC, and Pir, and GP, as visualized in coronal, sagittal and horizontal planes and (D) as plotted as percentage change in signal response. *P < 0.05; **P < 0.01. Data represent mean ± SEM.