Engineering a memory with LTD and LTP
Open accessAbstract
It has been proposed that memories are encoded by modification of synaptic strengths through cellular mechanisms such as long-term potentiation (LTP) and long-term depression (LTD). However, the causal link between these synaptic processes and memory has been difficult to demonstrate. Here we show that fear conditioning, a type of associative memory, can be inactivated and reactivated by LTD and LTP, respectively. We began by conditioning an animal to associate a foot shock with optogenetic stimulation of auditory inputs targeting the amygdala, a brain region known to be essential for fear conditioning. Subsequent optogenetic delivery of LTD conditioning to the auditory input inactivates memory of the shock. Then subsequent optogenetic delivery of LTP conditioning to the auditory input reactivates memory of the shock. Thus, we have engineered inactivation and reactivation of a memory using LTD and LTP, supporting a causal link between these synaptic processes and memory.
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Fear memories can be inactivated and reactivated via induction of LTP and LTD in amygdalar microcircuits.
“fear memories can be inactivated and reactivated via induction of LTP and LTD in amygdalar microcircuits148.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [148]
Fear-conditioned memories can be alternately erased and reinstated by long-term depression (LTD) and long-term potentiation (LTP), respectively, of a defined synaptic pathway.
“For example, fear-conditioned memories can be alternately erased and reinstated by long-term depression (LTD) and long-term potentiation (LTP), respectively, of a defined synaptic pathway42.”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [42]
Learning is implemented, at least in part, by changes in synaptic strength (synaptic plasticity).
“There is now agreement that learning is implemented, at least in part, by changes in synaptic strength (synaptic plasticity).”
From The right time to learn: Mechanisms and optimization of spaced learning (2016) · cites this paper as [42]
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- Authors
- Nabavi, S., Fox, R., Proulx, C. D., Lin, J. Y., Tsien, R. Y., & Malinow, R.
- Affiliations
- University of California San Diego (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Malinow, Roberto
- Venue
- Nature
- Published
- 2014-06-01
- Volume
- 511
- Issue
- 7509
- Pages
- 348-352
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4210354
- OpenAlex
- W1982864908
- Cited by
- 980
- References
- 36
- Citations by year
- 2026: 39 · 2025: 68 · 2024: 78 · 2023: 67 · 2022: 79 · 2021: 90 · 2020: 113 · 2019: 80 · 2018: 89 · 2017: 88 · 2016: 86 · 2015: 79 · 2014: 24
- FWCI
- 51.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG032132)
- National Institute of Mental Health (R01MH091119, R01MH049159, R37MH049159, MH049159)
- National Institute of Neurological Disorders and Stroke (NS27177, R37NS027177, R01NS027177)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- long-term potentiation, long-term depression, synaptic plasticity, memory formation, fear conditioning, optogenetics, amygdala, memory reactivation, associative memory, auditory input
- MeSH terms
- Amygdala, Animals, Conditioning, Psychological, Electric Stimulation, Electrophysiology, Fear, Male, Memory, Synaptic Transmission, Synapses, Rats, Sprague-Dawley, Long-Term Potentiation, Long-Term Synaptic Depression, Rats, Optogenetics
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