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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.

Author information

1
Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA 02215.
2
Department of Medicine, Harvard Medical School, Boston, MA 02215.
3
Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA 02215; c.ronald.kahn@joslin.harvard.edu.

Abstract

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.

KEYWORDS:

amygdala; cognition; hippocampus; insulin; metabolism

PMID:
30765523
PMCID:
PMC6442573
DOI:
10.1073/pnas.1817391116
[Indexed for MEDLINE]
Free PMC Article

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