CX3CR1 deficiency alters hippocampal-dependent plasticity phenomena blunting the effects of enriched environment
Open accessAbstract
In recent years several evidence demonstrated that some features of hippocampal biology, like neurogenesis, synaptic transmission, learning, and memory performances are deeply modulated by social, motor, and sensorial experiences. Fractalkine/CX(3)CL1 is a transmembrane chemokine abundantly expressed in the brain by neurons, where it modulates glutamatergic transmission and long-term plasticity processes regulating the intercellular communication between glia and neurons, being its specific receptor CX(3)CR1 expressed by microglia. In this paper we investigated the role of CX(3)CL1/CX(3)CR1 signaling on experience-dependent hippocampal plasticity processes. At this aim wt and CX(3)CR1(GFP/GFP) mice were exposed to long-lasting-enriched environment (EE) and the effects on hippocampal functions were studied by electrophysiological recordings of long-term potentiation of synaptic activity, behavioral tests of learning and memory in the Morris water maze paradigm and analysis of neurogenesis in the subgranular zone of the dentate gyrus (DG). We found that CX(3)CR1 deficiency increases hippocampal plasticity and spatial memory, blunting the potentiating effects of EE. In contrast, exposure to EE increased the number and migration of neural progenitors in the DG of both wt and CX(3)CR1(GFP/GFP) mice. These data indicate that CX(3)CL1/CX(3)CR1-mediated signaling is crucial for a normal experience-dependent modulation of hippocampal functions.
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Evidence suggests CX3CR1 plays an important role in the regulation of synaptic function, with CX3CR1 deficiency resulting in cognitive and LTP impairments indicative of altered synaptic plasticity.
“evidence suggests it plays an important role in the regulation of synaptic function, with CX3CR1 deficiency resulting in cognitive and LTP impairments indicative of altered synaptic plasticity [42, 43].”
From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [43]
The Discussion reports that under standard housing, CX3CR1-deficient mice had improved hippocampal LTP and spatial memory compared with wild-type mice, contrary to the claimed impairments. It also reports that deficiency blunted the additional benefits of an enriched environment, but that is not the same as impaired LTP and cognition at baseline. (LLM, conf=0.90)
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- Authors
- Maggi, L.
- Affiliations
- Istituto Pasteur (IT)
- Corresponding author
- Maggi, Laura
- ORCID
- Maggi, Laura
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2011
- Volume
- 5
- Pages
- 22-22
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC3198035
- OpenAlex
- W2005933589
- Cited by
- 149
- References
- 56
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 6 · 2022: 14 · 2021: 17 · 2020: 7 · 2019: 14 · 2018: 7 · 2017: 15 · 2016: 13 · 2015: 8 · 2014: 16 · 2013: 7 · 2012: 10
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Ministero della Salute
- Fondazione Pierfranco e Luisa Mariani
- Istituto Pasteur-Fondazione Cenci Bolognetti
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CX3CR1, fractalkine, microglia, environmental enrichment, hippocampal plasticity, long-term potentiation, spatial memory, dentate gyrus neurogenesis, experience-dependent plasticity, learning and memory
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