Role of Ca2+‐stimulated adenylyl cyclases in LTP and memory formation
Abstract
Studies with invertebrates and vertebrates have strongly implicated the CREB/CRE transcriptional pathway in long‐term memory (LTM) and transcriptionally‐dependent L‐LTP. It is hypothesized that LTM and L‐LTP are both dependent upon a Ca 2+ signal generated through activation of NMDA receptors. This review discusses evidence that Ca 2+ signals generated through activation of NMDA receptors coactivate the Erk/MAP kinase and cAMP signal transduction pathways. It is hypothesized that activation of these two regulatory pathways increases the transcription of a family of genes through the CREB/CRE transcriptional pathway. Gene disruption studies have shown that Ca 2+ activated adenylyl cyclases play a critical role in generating the cAMP signal required for LTM and L‐LTP. Although cAMP may be required for several events in this complex signal transduction cascade, one of the major roles of cAMP may be to support nuclear translocation of Erk/MAP kinase in hippocampal neurons.
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This rapid influx of calcium would trigger the initiation of a cascade in the phosphorylation of molecules involved in synaptic plasticity and in the formation of memories of the events that had occurred in phase 1.
“This rapid influx of calcium would trigger the initiation of a cascade in the phosphorylation of molecules involved in synaptic plasticity and in the formation of memories of the events that had occurred in phase 1 (Blair et al. [259]; Poser and Storm [260]; Lisman et al. [261]; Rongo [262]; Suenaga et al. [263]).”
From The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes-Dodson Law (2007) · cites this paper as Poser and Storm [260]
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“Ca2+-sensitive adenylyl cyclases are critical for mossy fiber/CA3 LTP In contrast to the NMDA receptor-dependent LTP, which is dependent upon increased postsynaptic Ca2+, mossy fiber LTP requires an increase in presynaptic Ca2+ (Zalutsky and Nicoll, 1990; Johnston et al., 1992).”
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- Authors
- Poser, S., & Storm, D. R.
- Affiliations
- Department of Pharmacology University of Washington Health Sciences Building, Mail Box 357750 Seattle WA 98195‐7750 USA
- University of Washington (US)
- Corresponding author
- Storm, Daniel R.
- ORCID
- Storm, Daniel R.
- Venue
- International Journal of Developmental Neuroscience
- Publisher
- Wiley
- Published
- 2001-05-22
- Volume
- 19
- Issue
- 4
- Pages
- 387-394
- ISSN
- 0736-5748 (ISSN-L)
- 1873-474X
- OpenAlex
- W2042250385
- Cited by
- 128
- References
- 10
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 2 · 2022: 1 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (DC04156, NS357056)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- long-term potentiation, long-term memory, NMDA receptor activation, cAMP signaling, ERK MAP kinase, hippocampal neurons, gene transcription, nuclear translocation, gene disruption
- MeSH terms
- Cyclic AMP, Adenylyl Cyclases, Animals, Calcium, Circadian Rhythm, Enzyme Activation, Hippocampus, Humans, Memory, Nerve Tissue Proteins, Neurons, Regulatory Sequences, Nucleic Acid, Transcription Factors, Transcription, Genetic, Receptors, N-Methyl-D-Aspartate, Cyclic AMP Response Element-Binding Protein, Long-Term Potentiation, Gene Expression Regulation, Developmental, Mossy Fibers, Hippocampal, Calcium Signaling, MAP Kinase Signaling System, Active Transport, Cell Nucleus, Mice, Activating Transcription Factor 2
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