Dysregulation of Presynaptic Calcium and Synaptic Plasticity in a Mouse Model of 22q11 Deletion Syndrome
Open accessAbstract
The 22q11 deletion syndrome (22q11DS) is characterized by cognitive decline and increased risk of psychiatric disorders, mainly schizophrenia. The molecular mechanisms of neuronal dysfunction in cognitive symptoms of 22q11DS are poorly understood. Here, we report that a mouse model of 22q11DS, the Df(16)1/ + mouse, exhibits substantially enhanced short- and long-term synaptic plasticity at hippocampal CA3–CA1 synapses, which coincides with deficits in hippocampus-dependent spatial memory. These changes are evident in mature but not young animals. Electrophysiological, two-photon imaging and glutamate uncaging, and electron microscopic assays in acute brain slices showed that enhanced neurotransmitter release but not altered postsynaptic function or structure caused these changes. Enhanced neurotransmitter release in Df(16)1/ + mice coincided with altered calcium kinetics in CA3 presynaptic terminals and upregulated sarco(endo)plasmic reticulum calcium-ATPase type 2 (SERCA2). SERCA inhibitors rescued synaptic phenotypes of Df(16)1/ + mice. Thus, presynaptic SERCA2 upregulation may be a pathogenic event contributing to the cognitive symptoms of 22q11DS.
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In the Df(16)1/+ mouse model of the 22q11.2 deletion, dendritic complexity, spine length, spine width, spine density, and PSD length are unaffected in the hippocampal CA1.
“In the Df(16)1/+ mouse model of the 22q11.2 deletion, dendritic complexity, spine length, spine width, spine density and PSD length are unaffected in the hippocampal CA1 [92].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [92]
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- Authors
- Earls, L. R., Bayazitov, I. T., Fricke, R. G., Berry, R. B., Illingworth, E., Mittleman, G., & Zakharenko, S. S.
- Affiliations
- St. Jude Children's Research Hospital (US)
- University of Salerno (IT)
- University of Memphis (US)
- Corresponding author
- Zakharenko, Stanislav S.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-11-24
- Volume
- 30
- Issue
- 47
- Pages
- 15843-15855
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3073555
- OpenAlex
- W2001092440
- Cited by
- 79
- References
- 69
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 10 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 5 · 2012: 3
- FWCI
- 2.07
- 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
- Kinship Foundation
- American Lebanese Syrian Associated Charities
- Searle Scholars Program
- National Institute of Mental Health (R01MH079079)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- 22q11.2 deletion syndrome, presynaptic calcium, synaptic plasticity, hippocampal CA3-CA1 synapses, spatial memory impairment, neurotransmitter release, SERCA2, Ca2+-ATPase, schizophrenia, cognitive decline, presynaptic terminals
- MeSH terms
- Animals, Calcium, Disease Models, Animal, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Neuronal Plasticity, Presynaptic Terminals, Mice, 22q11 Deletion Syndrome
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