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 1

Vibrissae stimulation leads to time-dependent brain activation in barrel field circuitry.

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Vibrissae stimulation leads to time-dependent brain activation in barrel...
(A) μPET imaging protocol. Rats were anesthetized with isoflurane (ISO) and placed on the scanner bed; unilateral vibrissae stimulation was initiated. Five minutes later, rats were injected i.v. with approximately 0.6 mCi of FDG and scanning commenced. Stimulation lasted for 15 minutes. (B) Time-dependent increases in contralateral FDG uptake in response to unilateral vibrissae stimulation; (C) afferent and efferent connectivity of the vibrissal MC. Par1, parietal cortex; S1bf, primary somatosensory cortex barrel field; RSA, agranular retrosplenial cortex; Po, posterolateral thalamus; CL, centrolateral thalamus; MDL, lateral part of mediodorsal thalamus; VPL, lateral part of ventroposterior thalamus; VM, ventromedial thalamus; PRh, perirhinal cortex. Adapted with permission from Experimental Brain Research (11).