Estradiol and raloxifene modulate hippocampal gamma oscillations during a spatial memory task

Anna Schroeder; Matthew Hudson; Xin Du; Yee Wen Candace Wu; Jay Nakamura; Maarten van den Buuse; Nigel C Jones; Rachel A Hill

doi:10.1016/j.psyneuen.2017.01.022

Estradiol and raloxifene modulate hippocampal gamma oscillations during a spatial memory task

Psychoneuroendocrinology. 2017 Apr:78:85-92. doi: 10.1016/j.psyneuen.2017.01.022. Epub 2017 Jan 23.

Authors

Anna Schroeder¹, Matthew Hudson², Xin Du³, Yee Wen Candace Wu⁴, Jay Nakamura³, Maarten van den Buuse⁵, Nigel C Jones², Rachel A Hill⁶

Affiliations

¹ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
² Department of Medicine (RMH), University of Melbourne, Melbourne, Australia.
³ Department of Psychiatry, Monash University, Melbourne, Australia.
⁴ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, Australia; Department of Pharmacology, University of Melbourne, Melbourne, Australia; The College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia; Department of Psychiatry, Monash University, Melbourne, Australia. Electronic address: rachel.hill@monash.edu.

PMID: 28183030
DOI: 10.1016/j.psyneuen.2017.01.022

Abstract

Previous work suggests that estradiol regulates the expression of hippocampal parvalbumin as well as hippocampus-dependent spatial memory in mice. Parvalbumin interneurons generate neuronal oscillatory activity in the gamma frequency range (30-80Hz) and gamma oscillations are closely linked with higher cognitive functions. Raloxifene, a selective estrogen receptor modulator, shows beneficial effects on human cognitive performance, and has few peripheral side effects unlike estradiol, but the biological mechanisms which underpin these benefits are not clear. This study aimed to investigate whether estradiol and raloxifene modulate hippocampal gamma-band oscillations during spatial memory performance. Prepubescent female mice were ovariectomized (OVX) and implanted with a subcutaneous pellet of either estradiol (E2), raloxifene or placebo. During adulthood, local field potentials were recorded from the dorsal hippocampus while mice were performing the Y-maze hippocampus-dependent spatial memory task. Ovariectomy caused deficits in spatial memory, accompanied by a significant reduction in hippocampal gamma oscillations, specifically during decision making. Estradiol as well as raloxifene rescued both behavioural and electrophysiological deficits. These data have significant implications for disorders of cognitive impairment where altered gamma oscillations are apparent, such as schizophrenia.

Keywords: Estradiol; Gamma oscillations; Hippocampus; Memory; Mice; Raloxifene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects*
Action Potentials / physiology
Animals
Estradiol / pharmacology*
Female
Gamma Rhythm / drug effects*
Gamma Rhythm / physiology
Hippocampus / drug effects*
Hippocampus / physiology
Mice
Ovariectomy
Raloxifene Hydrochloride / pharmacology*
Selective Estrogen Receptor Modulators / pharmacology*
Spatial Memory / drug effects*
Spatial Memory / physiology

Substances

Selective Estrogen Receptor Modulators
Raloxifene Hydrochloride
Estradiol