Requirement of a Critical Period of Transcription for Induction of a Late Phase of LTP
Abstract
Repeated high-frequency trains of stimuli induce long-term potentiation (LTP) in the CA1 region that persists for up to 8 hours in hippocampal slices and for days in intact animals. This long time course has made LTP an attractive model for certain forms of long-term memory in the mammalian brain. A hallmark of long-term memory in the intact animal is a requirement for transcription, and thus whether the late phase of LTP (L-LTP) requires transcription was investigated here. With the use of different inhibitors, it was found in rat hippocampal slices that the induction of L-LTP [produced either by tetanic stimulation or by application of the cyclic adenosine monophosphate (cAMP) analog Sp-cAMPS (Sp-cyclic adenosine 3′,5′-monophosphorothioate)] was selectively prevented when transcription was blocked immediately after tetanization or during application of cAMP. As with behavioral memory, this requirement for transcription had a critical time window. Thus, the late phase of LTP in the CA1 region requires transcription during a critical period, perhaps because cAMP-inducible genes must be expressed during this period.
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LTP that persists for several hours or more requires translation and transcription, which is reliant on transcription factors such as CREB.
“LTP that persists for several hours or more requires translation and transcription50,51, which is reliant on key transcription factors such as cyclic AMP-responsive element (CRE)-binding protein (CREB)52.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [50]
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- Authors
- Nguyen, P. V., Abel, T., & Kandel, E. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Columbia University Irving Medical Center (US)
- Venue
- Science
- Published
- 1994-08-19
- Volume
- 265
- Issue
- 5175
- Pages
- 1104-1107
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2005744880
- Cited by
- 888
- References
- 43
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 12 · 2023: 6 · 2022: 10 · 2021: 11 · 2020: 18 · 2019: 18 · 2018: 24 · 2017: 23 · 2016: 22 · 2015: 22 · 2014: 27 · 2013: 36 · 2012: 34
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01gm032099-14)
- National Institute of General Medical Sciences (GM 32099)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- long-term potentiation, transcription, CA1 region, hippocampus, cyclic AMP, tetanic stimulation, critical period, long-term memory, gene expression, memory consolidation
- MeSH terms
- Cyclic AMP, Animals, Dactinomycin, Dichlororibofuranosylbenzimidazole, Electric Stimulation, Evoked Potentials, Hippocampus, Male, Synaptic Transmission, Thionucleotides, Transcription, Genetic, Rats, Sprague-Dawley, Long-Term Potentiation, Pyramidal Cells, Rats, In Vitro Techniques
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