A Critical Period for Macromolecular Synthesis in Long-Term Heterosynaptic Facilitation in Aplysia
Abstract
Both long-term and short-term sensitization of the gill and siphon withdrawal reflex in Aplysia involve facilitation of the monosynaptic connections between the sensory and motor neurons. To analyze the relationship between these two forms of synaptic facilitation at the cellular and molecular level, this monosynaptic sensorimotor component of the gill-withdrawal reflex of Aplysia can be reconstituted in dissociated cell culture. Whereas one brief application of 1 μ M serotonin produced short-term facilitation in the sensorimotor connection that lasted minutes, five applications over 1.5 hours resulted in long-term facilitation that lasted more than 24 hours. Inhibitors of protein synthesis or RNA synthesis selectively blocked long-term facilitation, but not short-term facilitation, indicating that long-term facilitation requires the expression of gene products not essential for short-term facilitation. Moreover, the inhibitors only blocked long-term facilitation when given during the serotonin applications; the inhibitors did not block the facilitation when given either before or after serotonin application. These results parallel those for behavioral performance in vertebrates and indicate that the critical time window characteristic of the requirement for macromolecular synthesis in long-term heterosynaptic facilitation is not a property of complex circuitry, but an intrinsic characteristic of specific nerve cells and synaptic connections involved in the long-term storage of information.
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Learning and long-term memory formation are improved by enhanced histone acetylation, which could be improved by HDAC inhibitors.
“The synthesis of new proteins is necessary for long-term changes in synaptic plasticity and learning (132–134). In this context, learning and long-term memory formation are improved by enhanced histone acetylation (135), which could be improved by HDAC inhibitors (HDACi).”
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The 'standard' protocol (five 5-minute pulses of 5-HT, with uniform inter-stimulus intervals of 20 minutes) has been commonly used to induce LTF in empirical studies for ~30 years.
“The protocol termed the ‘standard’ protocol (five 5-minute pulses of 5-HT, with uniform inter-stimulus intervals of 20 minutes) (FIG. 4b) has been commonly used to induce LTF in empirical studies for ~30 years91.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [91]
The Standard protocol, consisting of five 5-min pulses of 5-HT with uniform 20-min interstimulus intervals, has been widely used in experimental studies since 1986.
“This 'Standard' protocol has been widely used in experimental studies since its introduction in 198623.”
From Computational design of enhanced learning protocols (2012) · cites this paper as [23]
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- Authors
- Montarolo, P. G., Goelet, P., Castellucci, V. F., Morgan, J., Kandel, E. R., & Schacher, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Science
- Published
- 1986-12-05
- Volume
- 234
- Issue
- 4781
- Pages
- 1249-1254
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2080480553
- Cited by
- 769
- References
- 39
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 19 · 2023: 8 · 2022: 10 · 2021: 7 · 2020: 8 · 2019: 8 · 2018: 13 · 2017: 16 · 2016: 8 · 2015: 14 · 2014: 14 · 2013: 20 · 2012: 17
- FWCI
- 7.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS19595)
- 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 › Neurobiology and Insect Physiology Research
- Keywords
- heterosynaptic facilitation, Aplysia, gill-withdrawal reflex, serotonin, protein synthesis, RNA synthesis, critical period, short-term facilitation, long-term memory storage, dissociated cell culture, sensitization
- MeSH terms
- Amanitins, Anisomycin, Aplysia, Cells, Cultured, Memory, Memory, Short-Term, Motor Neurons, Neurons, Afferent, Reflex, RNA, Messenger, Serotonin, Protein Biosynthesis
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