Localized Neuronal Outgrowth Induced by Long-Term Sensitization Training in Aplysia
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Biophysical, biochemical, and morphological studies have implicated sensory neurons as key sites of plasticity in the formation and retention of the memory of long-term sensitization in Aplysia californica. This study examined the effects of different sensitization training protocols on the structure of sensory neurons mediating the tail-siphon withdrawal reflex. A 4 d training period produced a robust localized outgrowth in these sensory neurons observed 24 hr after the end of training. These changes are consistent with previous results in siphon sensory neurons (Bailey and Chen, 1988a). In contrast, 1 d of sensitization training, which has been shown to effectively induce long-term behavioral sensitization and synaptic facilitation (Frost et al., 1985; Cleary et al., 1998), is not associated with morphological changes in tail sensory neurons at either 24 hr or 4 d after training. Similarly, a single treatment with the growth factor TGF-β, which also induced facilitation, did not alter sensory neuron morphology. The different effectiveness of the two protocols was not simply a reflection of the number of stimuli presented, because a 1 d massed training protocol did not produce sensitization 24 hr after training, nor did it induce neuronal outgrowth. These results suggest that extensive sensitization training is required to induce neuronal outgrowth in tail sensory neurons, indicating that the memory of long-term sensitization induced by 1 d of training is mechanistically different from that induced by 4 d of training. Moreover, the induction of a form of long-term sensitization associated with neuronal outgrowth does not appear to be a function of the amount of stimulation but does appear to be dependent on the temporal spacing of the stimulation over multiple days.
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Spaced training leads to improved memory in invertebrates such as Aplysia californica, Drosophila melanogaster and bees, and in rodents and non-human primates.
“Spaced training also leads to improved memory in invertebrates, such as the mollusk Aplysia californica11–14, Drosophila melanogaster15,16 and bees17, and in rodents18,19 and non-human primates20,21.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [13]
LTF at Aplysia californica sensorimotor synapses is associated with long-term sensitization (LTS) of withdrawal reflexes.
“LTF at these sensorimotor synapses is associated with a simple form of learning, long-term sensitization (LTS) of withdrawal reflexes.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [13]
In vivo, four spaced electrical stimuli with 30-minute intervals yielded LTS lasting more than 24 hours, with weak residual LTS detectable at 4 days, and repetition once per day for 4 days yielded much stronger LTS lasting more than 1 week.
“In vivo, four spaced electrical stimuli (with 30 minutes intervals between the stimuli) yielded LTS that lasted for more than 24 hours, with weak residual LTS being detectable at 4 days post-training, and repetition of this spaced protocol once per day for 4 days yielded much stronger LTS that lasted for more than 1 week13,57,58.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [13]
An effective protocol for LTS training in Aplysia californica is four trials with an inter-trial interval of 30 minutes, repeated four times with a 1-day inter-trial interval.
“Indeed, an effective protocol for LTS training in A. californica is the use of four trials with an inter-trial interval of 30 minutes, repeated four times with a 1-day inter-trial interval13.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [13]
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- Authors
- Wainwright, M. L., Zhang, H., Byrne, J. H., & Cleary, L. J.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-05-15
- Volume
- 22
- Issue
- 10
- Pages
- 4132-4141
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757634
- OpenAlex
- W1536186648
- Cited by
- 78
- References
- 52
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 4
- FWCI
- 1.28
- 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
- National Institutes of Health (5r01ns038100-03, NS07373, NS019895)
- National Institute of Mental Health (F31MH012176)
- National Institute of Neurological Disorders and Stroke (R01NS019895, T32NS007373)
- 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
- long-term sensitization, neurite outgrowth, sensory neurons, Aplysia californica, TGF-beta, synaptic facilitation, memory retention, neuroplasticity
- MeSH terms
- Animals, Aplysia, Behavior, Animal, Conditioning, Psychological, Electric Stimulation, Neuronal Plasticity, Neurons, Afferent, Reflex, Sensory Thresholds, Tail, Time Factors, Transforming Growth Factor beta, Neurites, Long-Term Potentiation, Ganglia, Invertebrate, In Vitro Techniques
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