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

doi:10.7554/eLife.19358

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

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 language	English (US)
Article number	e19358
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.19358
State	Published - Jan 4 2017

ASJC Scopus subject areas

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

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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.",

author = "Yu, {Xiao Wen} and Curlik, {Daniel M.} and Oh, {M. Matthew} and Yin, {Jerry C.P.} and Disterhoft, {John F.}",

note = "Funding Information: American Federation for Aging Research Glenn/AFAR Scholarship for Research in the Biology of Aging Xiao-Wen Yu National Institutes of Health T32 AG020506 Xiao-Wen Yu Daniel M Curlik II National Institutes of Health P30 AG13854 Daniel M Curlik II National Institutes of Health R01 NS063245 Jerry CP Yin National Institutes of Health R37 AG008796 John F Disterhoft National Institutes of Health RF1 AG017139 John F Disterhoft The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} Yu et al.",

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AU - Disterhoft, John F.

N1 - Funding Information: American Federation for Aging Research Glenn/AFAR Scholarship for Research in the Biology of Aging Xiao-Wen Yu National Institutes of Health T32 AG020506 Xiao-Wen Yu Daniel M Curlik II National Institutes of Health P30 AG13854 Daniel M Curlik II National Institutes of Health R01 NS063245 Jerry CP Yin National Institutes of Health R37 AG008796 John F Disterhoft National Institutes of Health RF1 AG017139 John F Disterhoft The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: © Yu et al.

PY - 2017/1/4

Y1 - 2017/1/4

N2 - 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

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