Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions
Abstract The hippocampus is a plastic brain area that shows functional segregation along its longitudinal axis, reflected by a higher level of long-term potentiation (LTP) in the CA1 region of the dorsal hippocampus (DH) compared to the ventral hippocampus (VH), but the mechanisms underlying this di...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02655-z |
| _version_ | 1811302359842684928 |
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| author | E. De Felice E. Gonçalves de Andrade M. T. Golia F. González Ibáñez M. Khakpour M. A. Di Castro S. Garofalo E. Di Pietro C. Benatti N. Brunello F. Tascedda B. Kaminska C. Limatola D. Ragozzino M. E. Tremblay S. Alboni L. Maggi |
| author_facet | E. De Felice E. Gonçalves de Andrade M. T. Golia F. González Ibáñez M. Khakpour M. A. Di Castro S. Garofalo E. Di Pietro C. Benatti N. Brunello F. Tascedda B. Kaminska C. Limatola D. Ragozzino M. E. Tremblay S. Alboni L. Maggi |
| author_sort | E. De Felice |
| collection | DOAJ |
| description | Abstract The hippocampus is a plastic brain area that shows functional segregation along its longitudinal axis, reflected by a higher level of long-term potentiation (LTP) in the CA1 region of the dorsal hippocampus (DH) compared to the ventral hippocampus (VH), but the mechanisms underlying this difference remain elusive. Numerous studies have highlighted the importance of microglia–neuronal communication in modulating synaptic transmission and hippocampal plasticity, although its role in physiological contexts is still largely unknown. We characterized in depth the features of microglia in the two hippocampal poles and investigated their contribution to CA1 plasticity under physiological conditions. We unveiled the influence of microglia in differentially modulating the amplitude of LTP in the DH and VH, showing that minocycline or PLX5622 treatment reduced LTP amplitude in the DH, while increasing it in the VH. This was recapitulated in Cx3cr1 knockout mice, indicating that microglia have a key role in setting the conditions for plasticity processes in a region-specific manner, and that the CX3CL1–CX3CR1 pathway is a key element in determining the basal level of CA1 LTP in the two regions. The observed LTP differences at the two poles were associated with transcriptional changes in the expression of genes encoding for Il-1, Tnf-α, Il-6, and Bdnf, essential players of neuronal plasticity. Furthermore, microglia in the CA1 SR region showed an increase in soma and a more extensive arborization, an increased prevalence of immature lysosomes accompanied by an elevation in mRNA expression of phagocytic markers Mertk and Cd68 and a surge in the expression of microglial outward K+ currents in the VH compared to DH, suggesting a distinct basal phenotypic state of microglia across the two hippocampal poles. Overall, we characterized the molecular, morphological, ultrastructural, and functional profile of microglia at the two poles, suggesting that modifications in hippocampal subregions related to different microglial statuses can contribute to dissect the phenotypical aspects of many diseases in which microglia are known to be involved. |
| first_indexed | 2024-04-13T07:26:40Z |
| format | Article |
| id | doaj.art-2e491deb8b694fdb90895be825c05662 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T07:26:40Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-2e491deb8b694fdb90895be825c056622022-12-22T02:56:27ZengBMCJournal of Neuroinflammation1742-20942022-12-0119112310.1186/s12974-022-02655-zMicroglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditionsE. De Felice0E. Gonçalves de Andrade1M. T. Golia2F. González Ibáñez3M. Khakpour4M. A. Di Castro5S. Garofalo6E. Di Pietro7C. Benatti8N. Brunello9F. Tascedda10B. Kaminska11C. Limatola12D. Ragozzino13M. E. Tremblay14S. Alboni15L. Maggi16Department of Physiology and Pharmacology, Sapienza University of RomeDivision of Medical Sciences, University of VictoriaDepartment of Physiology and Pharmacology, Sapienza University of RomeDivision of Medical Sciences, University of VictoriaDivision of Medical Sciences, University of VictoriaDepartment of Physiology and Pharmacology, Sapienza University of RomeDepartment of Physiology and Pharmacology, Sapienza University of RomeDepartment of Physiology and Pharmacology, Sapienza University of RomeDepartment of Life Sciences, University of Modena and Reggio EmiliaDepartment of Life Sciences, University of Modena and Reggio EmiliaDepartment of Life Sciences, University of Modena and Reggio EmiliaLaboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology of the Polish Academy of SciencesIRCCS NeuromedDepartment of Physiology and Pharmacology, Sapienza University of RomeDivision of Medical Sciences, University of VictoriaDepartment of Life Sciences, University of Modena and Reggio EmiliaDepartment of Physiology and Pharmacology, Sapienza University of RomeAbstract The hippocampus is a plastic brain area that shows functional segregation along its longitudinal axis, reflected by a higher level of long-term potentiation (LTP) in the CA1 region of the dorsal hippocampus (DH) compared to the ventral hippocampus (VH), but the mechanisms underlying this difference remain elusive. Numerous studies have highlighted the importance of microglia–neuronal communication in modulating synaptic transmission and hippocampal plasticity, although its role in physiological contexts is still largely unknown. We characterized in depth the features of microglia in the two hippocampal poles and investigated their contribution to CA1 plasticity under physiological conditions. We unveiled the influence of microglia in differentially modulating the amplitude of LTP in the DH and VH, showing that minocycline or PLX5622 treatment reduced LTP amplitude in the DH, while increasing it in the VH. This was recapitulated in Cx3cr1 knockout mice, indicating that microglia have a key role in setting the conditions for plasticity processes in a region-specific manner, and that the CX3CL1–CX3CR1 pathway is a key element in determining the basal level of CA1 LTP in the two regions. The observed LTP differences at the two poles were associated with transcriptional changes in the expression of genes encoding for Il-1, Tnf-α, Il-6, and Bdnf, essential players of neuronal plasticity. Furthermore, microglia in the CA1 SR region showed an increase in soma and a more extensive arborization, an increased prevalence of immature lysosomes accompanied by an elevation in mRNA expression of phagocytic markers Mertk and Cd68 and a surge in the expression of microglial outward K+ currents in the VH compared to DH, suggesting a distinct basal phenotypic state of microglia across the two hippocampal poles. Overall, we characterized the molecular, morphological, ultrastructural, and functional profile of microglia at the two poles, suggesting that modifications in hippocampal subregions related to different microglial statuses can contribute to dissect the phenotypical aspects of many diseases in which microglia are known to be involved.https://doi.org/10.1186/s12974-022-02655-zLTPDorsal hippocampusVentral hippocampusMicroglial morphologyMicroglial ultrastructureCX3CL1–CX3CR1 signaling |
| spellingShingle | E. De Felice E. Gonçalves de Andrade M. T. Golia F. González Ibáñez M. Khakpour M. A. Di Castro S. Garofalo E. Di Pietro C. Benatti N. Brunello F. Tascedda B. Kaminska C. Limatola D. Ragozzino M. E. Tremblay S. Alboni L. Maggi Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions Journal of Neuroinflammation LTP Dorsal hippocampus Ventral hippocampus Microglial morphology Microglial ultrastructure CX3CL1–CX3CR1 signaling |
| title | Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions |
| title_full | Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions |
| title_fullStr | Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions |
| title_full_unstemmed | Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions |
| title_short | Microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions |
| title_sort | microglial diversity along the hippocampal longitudinal axis impacts synaptic plasticity in adult male mice under homeostatic conditions |
| topic | LTP Dorsal hippocampus Ventral hippocampus Microglial morphology Microglial ultrastructure CX3CL1–CX3CR1 signaling |
| url | https://doi.org/10.1186/s12974-022-02655-z |
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