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

Xiao Wen Yu, Daniel M. Curlik, M Matthew Oh, Jerry C.P. Yin, John F Disterhoft*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere19358
JournaleLife
Volume6
DOIs
StatePublished - Jan 4 2017

Fingerprint

Cyclic AMP Response Element-Binding Protein
Long-Term Memory
Memory Disorders
Rats
Data storage equipment
Animals
Pyramidal Cells
Viruses
Cognition
Neurons
Young Adult
Rodentia
Hippocampus
Transcription Factors
Modulation
Water

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

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title = "CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats",
abstract = "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.",
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CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats. / Yu, Xiao Wen; Curlik, Daniel M.; Oh, M Matthew; Yin, Jerry C.P.; Disterhoft, John F.

In: eLife, Vol. 6, e19358, 04.01.2017.

Research output: Contribution to journalArticle

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AU - Yu, Xiao Wen

AU - Curlik, Daniel M.

AU - Oh, M Matthew

AU - Yin, Jerry C.P.

AU - Disterhoft, John F

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AB - 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.

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