Molecule-to-Circuit Disease Mechanisms of a Synaptic SNAREopathy
Open accessAbstract
Alten et al. present a detailed investigation of disease-causing SNAP25 mutations based on structural analysis, neurotransmitter release, and emerging circuit properties. They show that structurally clustered mutations within the SNAP25 SNARE motif cause similar functional defects and predict that alterations of spontaneous release are a novel disease mechanism.
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Area 24 and its projection target region in the caudate nucleus in marmosets are implicated in the detection/expression of changes in action-outcome contingencies for reward.
“More recently, area 24 and projection target region in the caudate nucleus in marmosets have also been implicated in the detection/expression of changes in actionoutcome contingencies for reward [206].”
From Prefrontal cortex and depression (2022) · cites this paper as [206]
The cited paper’s passages on pp. 1–2 discuss SNAP25 mutations and neurotransmitter release, not reward-related action–outcome contingencies. Searches for area 24, the marmoset caudate nucleus, and reward contingencies found no passage in our copy addressing the claim. (LLM, conf=0.78)
Experimental — accuracy not yet measuredFailure to detect changes in action-outcome contingencies (associated with disrupted areas 32/24 in monkeys and PLc in rodents) could contribute to negative biases in approach-avoidance decision making and despair/helplessness.
“a failure to detect changes in the contingencies between one's actions and their outcome (associated with disrupted function in both areas 32 and 24 in monkeys [206] and PLc in rodents [205,250]) could contribute not only to negative biases in approach-avoidance decision making but also despair/helplessness [232].”
From Prefrontal cortex and depression (2022) · cites this paper as [206]
The cited paper’s discussion of SNAP25 mutations and neurotransmitter release (pp. 1–2) does not address the claim’s proposed link to despair or helplessness. Searches for action–outcome contingencies, approach–avoidance decisions, and areas 32/24 or PLc found no relevant passage in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measuredCentral OFC regions may contribute via updating predictive stimuli involved in Pavlovian-to-Instrumental transfer.
“Different again may be the contribution of regions within central OFC, with their links to the updating of predictive stimuli which may be involved in the mechanisms by which predictive stimuli can influence goal-directed actions, known as Pavlovian-to-Instrumental transfer [206,235].”
From Prefrontal cortex and depression (2022) · cites this paper as [206]
The cited paper’s discussion of SNAP25 mutations and synaptic transmission (Molecule-to-Circuit Disease Mechanisms of a Synaptic SNAREopathy, pp. 1–2) does not address central OFC, predictive-stimulus updating, or Pavlovian-to-instrumental transfer. Searches for those terms and for goal-directed actions found no relevant passage in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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Cites
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- Authors
- Praschberger, R., Jacquemyn, J., & Verstreken, P.
- Affiliations
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- Corresponding author
- Verstreken, Patrik
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 109
- Issue
- 1
- Pages
- 1-3
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W3119399676
- Cited by
- 7
- References
- 11
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 5
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- Funders
- Vlaams Instituut voor Biotechnologie
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- SNAP-25, SNARE proteins, neurotransmitter release, spontaneous release, synaptic transmission, disease mechanisms
- MeSH terms
- Brain Diseases, Humans, Membrane Fusion, Synaptic Transmission, Protein Binding, SNARE Proteins, Synaptosomal-Associated Protein 25
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