Opposite effects of fear conditioning and extinction on dendritic spine remodelling.
Abstract
It is generally believed that fear extinction is a form of new learning that inhibits rather than erases previously acquired fear memories. Although this view has gained much support from behavioural and electrophysiological studies, the hypothesis that extinction causes the partial erasure of fear memories remains viable. Using transcranial two-photon microscopy, we investigated how neural circuits are modified by fear learning and extinction by examining the formation and elimination of postsynaptic dendritic spines of layer-V pyramidal neurons in the mouse frontal association cortex. Here we show that fear conditioning by pairing an auditory cue with a footshock increases the rate of spine elimination. By contrast, fear extinction by repeated presentation of the same auditory cue without a footshock increases the rate of spine formation. The degrees of spine remodelling induced by fear conditioning and extinction strongly correlate with the expression and extinction of conditioned fear responses, respectively. Notably, spine elimination and formation induced by fear conditioning and extinction occur on the same dendritic branches in a cue- and location-specific manner: cue-specific extinction causes formation of dendritic spines within a distance of two micrometres from spines that were eliminated after fear conditioning. Furthermore, reconditioning preferentially induces elimination of dendritic spines that were formed after extinction. Thus, within vastly complex neuronal networks, fear conditioning, extinction and reconditioning lead to opposing changes at the level of individual synapses. These findings also suggest that fear memory traces are partially erased after extinction.
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A fear conditioning paradigm that pairs auditory cues with foot shocks has demonstrated opposite effects in auditory and frontal cortex.
“For example, a fear conditioning paradigm that pairs auditory cues with foot shocks has demonstrated opposite effects in auditory and frontal cortex.”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Lai et al., 2012
In the fear conditioning paradigm, a spine eliminated during fear conditioning is usually replaced by a spine in its vicinity (within 2 μm) during fear extinction.
“Similar spatial selectivity of spine dynamics has been observed in the fear conditioning paradigm: a spine eliminated during fear conditioning is usually replaced by a spine in its vicinity (within 2 μm) during fear extinction (Lai et al., 2012).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Lai et al., 2012
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Self-citation
- Authors
- Lai, C. S. W., Franke, T. F., & Gan, W.-B.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- Corresponding author
- Gan, Wen-Biao
- Venue
- Nature
- Published
- 2012-02-19
- Volume
- 483
- Issue
- 7387
- Pages
- 87-91
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1980452424
- Cited by
- 392
- References
- 24
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 16 · 2023: 20 · 2022: 16 · 2021: 26 · 2020: 26 · 2019: 28 · 2018: 27 · 2017: 36 · 2016: 38 · 2015: 35 · 2014: 30 · 2013: 42 · 2012: 23
- FWCI
- 21.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS047325, NS047325)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- fear conditioning, fear extinction, spine formation, fear memory, reconditioning, layer 5 pyramidal neurons, frontal association cortex, synaptic plasticity
- MeSH terms
- Acoustic Stimulation, Animals, Conditioning, Classical, Cues, Electric Stimulation, Extinction, Psychological, Extremities, Fear, Frontal Lobe, Male, Mice, Inbred C57BL, Mice, Transgenic, Models, Neurological, Neuronal Plasticity, Pyramidal Cells, Dendritic Spines, Mice
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