5-Hydroxytryptamine induces a protein kinase A/mitogen-activated protein kinase-mediated and macromolecular synthesis-dependent late phase of long-term potentiation in the amygdala
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The amygdala is a critical site for the acquisition of learned fear memory in mammals, and the formation and long-term maintenance of fear memories are thought to be associated with changes of synaptic strength in the amygdala. Here we report that serotonin (5-hydroxytryptamine; 5-HT), a modulatory neurotransmitter known to be linked to learned fearful and emotional behavior, has dual effects on excitatory synaptic transmission in the basolateral amygdala. There is an early depression of synaptic transmission lasting 30–50 min, mediated by 5-HT 1A, and a late, long-lasting facilitation lasting >5 h in slice recordings, mediated by the 5-HT 4 receptor. 5-HT late phase long-term potentiation (L-LTP) is blocked by inhibitors of either protein kinase A (PKA) and/or mitogen-activated kinase (MAPK) and requires new protein synthesis and gene transcription. Moreover, the 5-HT-induced L-LTP in neurons of amygdala is blocked by the actin inhibitor cytochalasin D, suggesting that 5-HT stimulates a cytoskeletal rearrangement. These results show, for the first time, that 5-HT can produce long-lasting facilitation of synaptic transmission in the amygdala and provides evidence for the possible synaptic role of 5-HT in long-term memory for learned fear.
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5-HT1A receptors fine-tune LTP in the amygdala during fear conditioning.
“For example 5-HT 1A -receptors fine-tune LTP in the amygdala during fear conditioning (Huang and Kandel, 2007;Johansen et al., 2011).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Huang and Kandel, 2007
In the Results section ('5-HT has different short-term and long-term effects on synaptic plasticity in amygdala,' Fig. 2; page not specified), blocking 5-HT1A reduced early synaptic depression but did not affect late LTP; blocking 5-HT4 abolished the long-term facilitation. The Introduction links amygdala LTP to fear conditioning, but the paper does not show 5-HT1A receptors fine-tuning LTP during fear conditioning. (LLM, conf=0.88)
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References 86 · Cited by 99
Research works printed but not linked: 2
- Azmitia EC, Gannon PJ (1986) The primate serotonergic system: a review of human and animal studies and a report on Macaca fascicularis. Adv Neu- rol 43:407-468.
- Barnes NM, Sharp T (1999) A review of central 5-HT receptors and their function. Neuropharmacology 38:1083-1152.
- Authors
- Huang, Y.-Y., & Kandel, E. R.
- Affiliations
- Columbia University (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Kandel, Eric R.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-03-21
- Volume
- 27
- Issue
- 12
- Pages
- 3111-3119
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672482
- OpenAlex
- W2002457970
- Cited by
- 99
- References
- 86
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 10 · 2013: 5 · 2012: 3
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (MH50733)
- National Institutes of Health
- National Institute of Mental Health (P50MH050733, MH-50733)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- serotonin, long-term potentiation, amygdala, basolateral amygdala, 5-HT1A receptor, 5-HT4 receptor, protein kinase A, mitogen-activated protein kinase, synaptic transmission, fear memory, protein synthesis, actin cytoskeleton, cytochalasin D, gene transcription
- MeSH terms
- Amygdala, Animals, Learning, Mice, Inbred C57BL, Neuronal Plasticity, Serotonin, Long-Term Potentiation, Cyclic AMP-Dependent Protein Kinases, Mitogen-Activated Protein Kinases, Mice
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