The progesterone-induced enhancement of object recognition memory consolidation involves activation of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) pathways in the dorsal hippocampus. Horm Behav 2012 Apr;61(4):487-95
Date
01/24/2012Pubmed ID
22265866Pubmed Central ID
PMC3401043DOI
10.1016/j.yhbeh.2012.01.004Scopus ID
2-s2.0-84859100570 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
Although much recent work has elucidated the biochemical mechanisms underlying the modulation of memory by 17β-estradiol, little is known about the signaling events through which progesterone (P) regulates memory. We recently demonstrated that immediate post-training infusion of P into the dorsal hippocampus enhances object recognition memory consolidation in young ovariectomized female mice (Orr et al., 2009). The goal of the present study was to identify the biochemical alterations that might underlie this mnemonic enhancement. We hypothesized that the P-induced enhancement of object recognition would be dependent on activation of the ERK and mTOR pathways. In young ovariectomized mice, we found that bilateral dorsal hippocampal infusion of P significantly increased levels of phospho-p42 ERK and the mTOR substrate S6K in the dorsal hippocampus 5 min after infusion. Phospho-p42 ERK levels were downregulated 15 min after infusion and returned to baseline 30 min after infusion, suggesting a biphasic effect of P on ERK activation. Dorsal hippocampal ERK and mTOR activation were necessary for P to facilitate memory consolidation, as suggested by the fact that inhibitors of both pathways infused into the dorsal hippocampus immediately after training blocked the P-induced enhancement of object recognition. Collectively, these data provide the first demonstration that the ability of P to enhance memory consolidation depends on the rapid activation of cell signaling and protein synthesis pathways in the dorsal hippocampus.
Author List
Orr PT, Rubin AJ, Fan L, Kent BA, Frick KMAuthor
Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
Butadienes
Data Interpretation, Statistical
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases
Female
Hippocampus
Memory
Mice
Mice, Inbred C57BL
Microinjections
Mitogen-Activated Protein Kinase Kinases
Nitriles
Ovariectomy
Phosphorylation
Progesterone
Protein Kinase Inhibitors
Ribosomal Protein S6 Kinases, 90-kDa
Signal Transduction
TOR Serine-Threonine Kinases
