Format

Send to

Choose Destination
Cell Metab. 2015 Apr 7;21(4):628-36. doi: 10.1016/j.cmet.2015.03.004.

Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism.

Author information

1
Center for Mitochondrial and Epigenomic Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: lpei@mail.med.upenn.edu.
2
Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
4
Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
5
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
6
Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead, New South Wales 2145, Australia.
7
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
8
Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu.

Abstract

Neurons utilize mitochondrial oxidative phosphorylation (OxPhos) to generate energy essential for survival, function, and behavioral output. Unlike most cells that burn both fat and sugar, neurons only burn sugar. Despite its importance, how neurons meet the increased energy demands of complex behaviors such as learning and memory is poorly understood. Here we show that the estrogen-related receptor gamma (ERRγ) orchestrates the expression of a distinct neural gene network promoting mitochondrial oxidative metabolism that reflects the extraordinary neuronal dependence on glucose. ERRγ(-/-) neurons exhibit decreased metabolic capacity. Impairment of long-term potentiation (LTP) in ERRγ(-/-) hippocampal slices can be fully rescued by the mitochondrial OxPhos substrate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ in cerebral cortex and hippocampus exhibit defects in spatial learning and memory. These findings implicate neuronal ERRγ in the metabolic adaptations required for memory formation.

PMID:
25863252
PMCID:
PMC4393848
DOI:
10.1016/j.cmet.2015.03.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center