Central amygdala PKC-δ^+ neurons mediate the influence of multiple anorexigenic signals
Feeding can be inhibited by multiple cues, including those associated with satiety, sickness or unpalatable food. How such anorexigenic signals inhibit feeding at the neural circuit level is not completely understood. Although some inhibitory circuits have been identified, it is not yet clear whether distinct anorexigenic influences are processed in a convergent or parallel manner. The amygdala central nucleus (CEA) has been implicated in feeding control, but its role is controversial. The lateral subdivision of CEA (CEl) contains a subpopulation of GABAergic neurons that are marked by protein kinase C-δ (PKC-δ). We found that CEl PKC-δ^+ neurons in mice were activated by diverse anorexigenic signals in vivo, were required for the inhibition of feeding by such signals and strongly suppressed food intake when activated. They received presynaptic inputs from anatomically distributed neurons activated by different anorexigenic agents. Our data suggest that CEl PKC-δ^+ neurons constitute an important node that mediates the influence of multiple anorexigenic signals.
© 2014 Nature America, Inc. Received 31 March 2014. Accepted 22 June 2014. Published online 27 July 2014. We thank B. Lowell (Beth Israel Deaconess Medical Center) for providing Cre-dependent DREADD constructs and viruses for pilot experiments, C. Saper (Beth Israel Deaconess Medical Center) for providing the original hrGFP construct, Z.J. Huang (Cold Spring Harbor Laboratory) for CRF-Cre mice, the Allen Institute for Brain Science for Tac2-Cre mice, C. Xiao and H. Lester for electrophysiology training and advice, and K. Deisseroth (Stanford University) for providing viruses for optogenetics. We thank J.S. Chang, C. Chiu and A. Chang for technical assistance on histology and behavior scoring, M. Martinez and M. McCardle for tail genotyping, G. Mosconi and C. Chiu for lab management, and G. Mancuso for administrative support. This work was supported by US National Institutes of Health grants R01MH085082 and MH070053, and a grant from the Klarman Foundation to D.J.A. H.C. is supported by a postdoctoral fellowship of the Hilda and Preston Davis Foundation and a NARSAD Young Investigator Award. D.J.A. receives funding from the Howard Hughes Medical Institute. Author Contributions: H.C. designed and performed the experiments and wrote the manuscript. W.H. generated BAC constructs for PKC-δ+ transgenic mice. T.E.A. made the virus constructs for Cre-out ChR2 and Cre-out eNpHR. D.J.A. contributed to experimental design and wrote the manuscript.
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