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Long-Range Connectivity Defines Behavioral Specificity of Amygdala Neurons
Open accessAbstract
Memories are acquired and encoded within large-scale neuronal networks spanning different brain areas. The anatomical and functional specificity of such long-range interactions and their role in learning is poorly understood. The amygdala and the medial prefrontal cortex (mPFC) are interconnected brain structures involved in the extinction of conditioned fear. Here, we show that a defined subpopulation of basal amygdala (BA) projection neurons targeting the prelimbic (PL) subdivision of mPFC is active during states of high fear, whereas BA neurons targeting the infralimbic (IL) subdivision are recruited, and exhibit cell-type-specific plasticity, during fear extinction. Pathway-specific optogenetic manipulations demonstrate that the activity balance between pathways is causally involved in fear extinction. Together, our findings demonstrate that, although intermingled locally, long-range connectivity defines distinct subpopulations of amygdala projection neurons and indicate that the formation of long-term extinction memories depends on the balance of activity between two defined amygdala-prefrontal pathways.
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“There is evidence to suggest that there is a dorso-ventral topographic segregation of BLA input to the mPFC; more dorsal projections (to PL) encode threat-stimulating information while more ventral projections (to IL) encode threat extinction-related information [51].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [51]
In the citing paper
“Moreover, optogenetic excitation of BLA→dmPFC PNs has been shown to increase conditioned fear after extinction (19).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [19]
In the citing paper
“By contrast, extinction of the learned fear association increases activity in basal amygdala neurons targeting the infralimbic cortex105.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [105]
In the citing paper
“During auditory fear conditioning, activity in basal amygdala neurons projecting to the prelimbic cortex is increased105”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [105]
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BackgroundSpontaneous Recovery of Fear Reverses Extinction-Induced Excitability of Infralimbic Neurons
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BackgroundLearning rules for aversive associative memory formation
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Astrocytes enable amygdala neural representations supporting memory
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“Specifically, chronic ethanol enhances excitability by reducing SK channel currents, SK-mediated mAHP amplitude, and SK3 subunit protein expression in NAC core MSNs (Hopf et al., 2010; Shan et al., 2019).”
BackgroundInfluentialTargeting drug or gene delivery to the phrenic motoneuron pool
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Enriched Environment Shortens the Duration of Action Potentials in Cerebellar Granule Cells
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“Therefore, the same neurons in themPFC could integrate spatial information provided by the hippocampus (Spellman et al. 2015) and emotional information from the amygdala (Senn et al. 2014) as competing inputs for subsequent cortical and subcortical processing.”
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Metadata
- Authors
- Senn, V., Wolff, S. B. E., Herry, C., Grenier, F., Ehrlich, I., Gründemann, J., Fadok, J. P., Müller, C., Letzkus, J. J., & Lüthi, A.
- Affiliations
- University of Basel (CH)
- Friedrich Miescher Institute (CH)
- Corresponding author
- Lüthi, Andreas
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 81
- Issue
- 2
- Pages
- 428-437
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1977502547
- Cited by
- 522
- References
- 38
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 35 · 2023: 35 · 2022: 40 · 2021: 55 · 2020: 45 · 2019: 52 · 2018: 55 · 2017: 47 · 2016: 30 · 2015: 49 · 2014: 34
- FWCI
- 29.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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
- amygdala, medial prefrontal cortex, fear extinction, long-range connectivity, prelimbic cortex, infralimbic cortex, memory extinction, optogenetic manipulation, fear conditioning
- MeSH terms
- Channelrhodopsins, Acoustic Stimulation, Action Potentials, Amygdala, Analysis of Variance, Animals, Bacterial Proteins, Biophysics, Cell Count, Conditioning, Classical, Elapid Venoms, Electric Stimulation, Extinction, Psychological, Fear, Hippocampus, Light, Luminescent Proteins, Male, Neural Pathways, Neurons, Peptides, Time Factors, Oncogene Proteins v-fos, Prefrontal Cortex, Herpesvirus 1, Human, Patch-Clamp Techniques, Mice, Biophysical Phenomena, Optogenetics, In Vitro Techniques
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