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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 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]
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Maphis, N., Xu, G., Kokiko-Cochran, O. N., Jiang, S., Cardona, A., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Brain · doi:10.1093/brain/awv081 · Cited by 595
Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K., & Tremblay, M. (2017) · The Journal of Physiology · doi:10.1113/jp272134 · Cited by 562
Hoshiko, M., Arnoux, I., Avignone, E., Yamamoto, N., & Audinat, E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1167-12.2012 · Cited by 384
“Several studies on adult rodents have reported that CX3CL1/R1 signaling, probably by controlling the activation state of MGCs, has an impact on functional properties and plasticity of hippocampal glutamate synapses (Ragozzino et al., 2006; Maggi et al., 2011; Rogers et al., 2011).”
BackgroundBeumer, W., Gibney, S. M., Drexhage, R. C., Pont-Lezica, L., Doorduin, J., Klein, H. C., Steiner, J., Connor, T. J., Harkin, A., Versnel, M. A., et al. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0212100 · Cited by 347
Neuron–glia crosstalk in health and disease: fractalkine and CX 3 CR1 take centre stage
Sheridan, G. K., & Murphy, K. J. (2013) · Open Biology · doi:10.1098/rsob.130181 · Cited by 358
Metadata
- 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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