Serotonin Induces Temporally and Mechanistically Distinct Phases of Persistent PKA Activity in Aplysia Sensory Neurons
Open accessAbstract
The cAMP signaling cascade has been implicated in several stages of memory formation. We have examined activation of this cascade by serotonin (5-HT) in the sensory neurons of Aplysia. We find that different patterns of 5-HT exposure induce three distinct modes of PKA activation. First, a single 5 min pulse induces transient (5 min) PKA activation that requires neither transcription nor translation. Second, 4-5 pulses induce intermediate-term persistent activation (3 hr duration) that requires translation but not transcription. Third, 5 pulses of 5-HT, as well as continuous (90 min) exposure, induce long-term persistent activation 20 hr later, which requires both transcription and translation. Thus, in the sensory neurons, different patterns of 5-HT give rise to three independent phases of PKA activation that differ in their induction requirements, their temporal profiles, and their molecular mechanisms.
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LTF and LTP both rely on PKA and ERK activation.
“For example, LTF and LTP both rely on PKA and ERK activation12,92,98”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [92]
MAPK activity rises and decays more slowly, not peaking until ~45 minutes after a pulse.
“MAPK activity rises and decays more slowly, not peaking until ~45 minutes after a pulse.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [92]
In response to each 5-HT pulse, PKA activity increases rapidly and decays rapidly.
“In response to each 5-HT pulse, PKA activity increases rapidly and decays rapidly (FIG. 4c).”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [92]
The PKA and ERK cascades are necessary to induce long-term synaptic facilitation (LTF) in Aplysia.
“Two biochemical cascades required for LTF are those that mediate activation of protein kinase A (PKA)12–15 and the MAP kinase isoform termed extracellular signal-regulated kinase (ERK)16–18.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [13]
Following a single 5-HT stimulus, PKA is activated rapidly but transiently, returning to near basal levels within 15 min.
“Following a single 5-HT stimulus, PKA is activated rapidly but transiently, with activity returning to near basal levels within 15 min13.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [13]
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References 57 · Cited by 128
- Authors
- Müller, U., & Carew, T. J.
- Affiliations
- Freie Universität Berlin (DE)
- Yale University (US)
- Corresponding author
- Carew, Thomas J
- ORCID
- Carew, Thomas J
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1998-12
- Volume
- 21
- Issue
- 6
- Pages
- 1423-1434
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1979412265
- Cited by
- 128
- References
- 57
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 5
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01 MH-141083)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- serotonin, protein kinase A, cAMP signaling, memory formation, transcription, translation (biology), synaptic plasticity
- MeSH terms
- Cyclic AMP, Animals, Aplysia, Enzyme Activation, Kinetics, Memory, Neurons, Afferent, Phosphorylation, Serotonin, Time Factors, Transcription, Genetic, Protein Biosynthesis, Signal Transduction, Gene Expression Regulation, Enzymologic, Cyclic AMP-Dependent Protein Kinases, Ganglia, Invertebrate, In Vitro Techniques
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