CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats

• Published in: eLife Vol. 6
• Main Authors: Yu, Xiao-Wen, Curlik, Daniel M, Oh, M Matthew, Yin, Jerry Cp, Disterhoft, John F
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 04.01.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Age; Aging; Animal behavior; Animals; CA1 Region, Hippocampal - physiology; cognition; Cognitive ability; CREB; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - biosynthesis; Excitability; Gene Expression; Genetic aspects; Kinases; Long term memory; Memory; Memory, Long-Term; Molecular modelling; Neuroscience; Observations; Proteins; Pyramidal cells; Rats; Rodents; Statistical analysis; Vectors (Biology); Young adults; CREB; memory; aging; cognition; rat; neuroscience
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.19358

The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline.