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Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6379-6384. doi: 10.1073/pnas.1817391116. Epub 2019 Feb 14.

Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior.

Soto M1,2, Cai W1,2, Konishi M1,2, Kahn CR3,2.

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Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA 02215.
Department of Medicine, Harvard Medical School, Boston, MA 02215.
Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA 02215;


Previous studies have shown that insulin and IGF-1 signaling in the brain, especially the hypothalamus, is important for regulation of systemic metabolism. Here, we develop mice in which we have specifically inactivated both insulin receptors (IRs) and IGF-1 receptors (IGF1Rs) in the hippocampus (Hippo-DKO) or central amygdala (CeA-DKO) by stereotaxic delivery of AAV-Cre into IRlox/lox/IGF1Rlox/lox mice. Consequently, both Hippo-DKO and CeA-DKO mice have decreased levels of the GluA1 subunit of glutamate AMPA receptor and display increased anxiety-like behavior, impaired cognition, and metabolic abnormalities, including glucose intolerance. Hippo-DKO mice also display abnormal spatial learning and memory whereas CeA-DKO mice have impaired cold-induced thermogenesis. Thus, insulin/IGF-1 signaling has common roles in the hippocampus and central amygdala, affecting synaptic function, systemic glucose homeostasis, behavior, and cognition. In addition, in the hippocampus, insulin/IGF-1 signaling is important for spatial learning and memory whereas insulin/IGF-1 signaling in the central amygdala controls thermogenesis via regulation of neural circuits innervating interscapular brown adipose tissue.


amygdala; cognition; hippocampus; insulin; metabolism

[Indexed for MEDLINE]
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