Estradiol and raloxifene modulate hippocampal gamma oscillations during a spatial memory task.
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.
The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia.
Anna
A
Schroeder
Department of Medicine (RMH), University of Melbourne, Melbourne, Australia.
Matthew
M
Hudson
Department of Psychiatry, Monash University, Melbourne, Australia.
Xin
X
Du
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yee Wen Candace
YWC
Wu
Department of Psychiatry, Monash University, Melbourne, Australia.
Jay
J
Nakamura
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.
Maarten
M
van den Buuse
Department of Medicine (RMH), University of Melbourne, Melbourne, Australia.
Nigel C
NC
Jones
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.
Rachel A
RA
Hill
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D065818:Gamma Rhythm / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol
Estradiol; Gamma oscillations; Hippocampus; Memory; Mice; Raloxifene