A Singer, F Trigo, L Vinel, O Gruere, I Llano, Martin Oheim
{"title":"小鼠小脑法尼亚纳斯细胞的形态学和电生理学特征初探","authors":"A Singer, F Trigo, L Vinel, O Gruere, I Llano, Martin Oheim","doi":"10.1113/JP285949","DOIUrl":null,"url":null,"abstract":"<p><p>Fañanas cells (FCs) are cerebellar glia of unknown function. First described more than a century ago, they have been almost absent from the scientific literature ever since. Here, we combined whole-cell, patch clamp recordings, near-UV laser photolysis, dye-loading and confocal imaging for a first characterization of FCs in terms of their morphology, electrophysiology and glutamate-evoked currents. We identified FCs of the molecular layer in cerebellar slices by their stubby process and small cell bodies. Despite their more compact shape compared to Bergmann glia (BGs), FCs showed similar membrane resistances and basal currents, suggesting that these passive currents are partly a result of electrical coupling between neighbouring glia. Dye filling and pharmacological experiments confirmed both homo- and heterotypic gap-junction coupling among FCs and BGs. Parallel-fibre stimulation evoked TTX-sensitive slow inward currents in FCs that were partially blocked by NBQX but not APV. Occasionally, we observed superimposed fast (milliseconds) current transients. Near-UV flash photolysis of MNI-caged glutamate revealed rapid desensitization of these AMPA-receptor mediated currents, which fully recovered only for stimulation intervals >500 ms. We mapped the highest current densities in proximal processes. We conclude that FCs respond with fast AMPA currents to local glutamate release and they integrate ambient glutamate rises to a slow inward current. Interestingly, we found FCs to prevail throughout adulthood at stable but different densities among cerebellar lobules, with the highest cell densities in lobules I-II and X. Our results strongly suggest that FCs are not just displaced BGs, and that they may have lobule-specific functions - both locally and at the circuit level, yet to be uncovered. KEY POINTS: Using whole-cell recordings and near-UV laser photolyisis of caged glutamate, we provide a first characterization of cells of Fañanas (FCs) in mouse cerebellar slices. FCs are present from postnatal day 5 onward throughout adulthood and have a lobule- dependent density. Parallel-fibre stimulation generates biphasic, predominantly AMPA-mediated currents in FCs. Currents induced in FCs by parallel fibre stimulation are not NMDA receptor-dependent and are enhanced upon glutamate-transporter block with TBOA. Local near-UV glutamate uncaging indicates that FCs can detect fast glutamatergic inputs on the millisecond-time scale. FCs functionally integrate into the glial syncytium.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A first morphological and electrophysiological characterization of Fañanas cells of the mouse cerebellum.\",\"authors\":\"A Singer, F Trigo, L Vinel, O Gruere, I Llano, Martin Oheim\",\"doi\":\"10.1113/JP285949\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Fañanas cells (FCs) are cerebellar glia of unknown function. First described more than a century ago, they have been almost absent from the scientific literature ever since. Here, we combined whole-cell, patch clamp recordings, near-UV laser photolysis, dye-loading and confocal imaging for a first characterization of FCs in terms of their morphology, electrophysiology and glutamate-evoked currents. We identified FCs of the molecular layer in cerebellar slices by their stubby process and small cell bodies. Despite their more compact shape compared to Bergmann glia (BGs), FCs showed similar membrane resistances and basal currents, suggesting that these passive currents are partly a result of electrical coupling between neighbouring glia. Dye filling and pharmacological experiments confirmed both homo- and heterotypic gap-junction coupling among FCs and BGs. Parallel-fibre stimulation evoked TTX-sensitive slow inward currents in FCs that were partially blocked by NBQX but not APV. Occasionally, we observed superimposed fast (milliseconds) current transients. Near-UV flash photolysis of MNI-caged glutamate revealed rapid desensitization of these AMPA-receptor mediated currents, which fully recovered only for stimulation intervals >500 ms. We mapped the highest current densities in proximal processes. We conclude that FCs respond with fast AMPA currents to local glutamate release and they integrate ambient glutamate rises to a slow inward current. Interestingly, we found FCs to prevail throughout adulthood at stable but different densities among cerebellar lobules, with the highest cell densities in lobules I-II and X. Our results strongly suggest that FCs are not just displaced BGs, and that they may have lobule-specific functions - both locally and at the circuit level, yet to be uncovered. KEY POINTS: Using whole-cell recordings and near-UV laser photolyisis of caged glutamate, we provide a first characterization of cells of Fañanas (FCs) in mouse cerebellar slices. FCs are present from postnatal day 5 onward throughout adulthood and have a lobule- dependent density. Parallel-fibre stimulation generates biphasic, predominantly AMPA-mediated currents in FCs. Currents induced in FCs by parallel fibre stimulation are not NMDA receptor-dependent and are enhanced upon glutamate-transporter block with TBOA. Local near-UV glutamate uncaging indicates that FCs can detect fast glutamatergic inputs on the millisecond-time scale. FCs functionally integrate into the glial syncytium.</p>\",\"PeriodicalId\":50088,\"journal\":{\"name\":\"Journal of Physiology-London\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-01-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Physiology-London\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1113/JP285949\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Physiology-London","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1113/JP285949","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
A first morphological and electrophysiological characterization of Fañanas cells of the mouse cerebellum.
Fañanas cells (FCs) are cerebellar glia of unknown function. First described more than a century ago, they have been almost absent from the scientific literature ever since. Here, we combined whole-cell, patch clamp recordings, near-UV laser photolysis, dye-loading and confocal imaging for a first characterization of FCs in terms of their morphology, electrophysiology and glutamate-evoked currents. We identified FCs of the molecular layer in cerebellar slices by their stubby process and small cell bodies. Despite their more compact shape compared to Bergmann glia (BGs), FCs showed similar membrane resistances and basal currents, suggesting that these passive currents are partly a result of electrical coupling between neighbouring glia. Dye filling and pharmacological experiments confirmed both homo- and heterotypic gap-junction coupling among FCs and BGs. Parallel-fibre stimulation evoked TTX-sensitive slow inward currents in FCs that were partially blocked by NBQX but not APV. Occasionally, we observed superimposed fast (milliseconds) current transients. Near-UV flash photolysis of MNI-caged glutamate revealed rapid desensitization of these AMPA-receptor mediated currents, which fully recovered only for stimulation intervals >500 ms. We mapped the highest current densities in proximal processes. We conclude that FCs respond with fast AMPA currents to local glutamate release and they integrate ambient glutamate rises to a slow inward current. Interestingly, we found FCs to prevail throughout adulthood at stable but different densities among cerebellar lobules, with the highest cell densities in lobules I-II and X. Our results strongly suggest that FCs are not just displaced BGs, and that they may have lobule-specific functions - both locally and at the circuit level, yet to be uncovered. KEY POINTS: Using whole-cell recordings and near-UV laser photolyisis of caged glutamate, we provide a first characterization of cells of Fañanas (FCs) in mouse cerebellar slices. FCs are present from postnatal day 5 onward throughout adulthood and have a lobule- dependent density. Parallel-fibre stimulation generates biphasic, predominantly AMPA-mediated currents in FCs. Currents induced in FCs by parallel fibre stimulation are not NMDA receptor-dependent and are enhanced upon glutamate-transporter block with TBOA. Local near-UV glutamate uncaging indicates that FCs can detect fast glutamatergic inputs on the millisecond-time scale. FCs functionally integrate into the glial syncytium.
期刊介绍:
The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew.
The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.