Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry
Abstract Plasticity and homeostatic mechanisms allow neural networks to maintain proper function while responding to physiological challenges. Despite previous work investigating morphological and synaptic effects of brain-derived neurotrophic factor (BDNF), the most prevalent growth factor in the c...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05638-9 |
| _version_ | 1797376875153063936 |
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| author | Kate M. O’Neill Erin D. Anderson Shoutik Mukherjee Srinivasa Gandu Sara A. McEwan Anton Omelchenko Ana R. Rodriguez Wolfgang Losert David F. Meaney Behtash Babadi Bonnie L. Firestein |
| author_facet | Kate M. O’Neill Erin D. Anderson Shoutik Mukherjee Srinivasa Gandu Sara A. McEwan Anton Omelchenko Ana R. Rodriguez Wolfgang Losert David F. Meaney Behtash Babadi Bonnie L. Firestein |
| author_sort | Kate M. O’Neill |
| collection | DOAJ |
| description | Abstract Plasticity and homeostatic mechanisms allow neural networks to maintain proper function while responding to physiological challenges. Despite previous work investigating morphological and synaptic effects of brain-derived neurotrophic factor (BDNF), the most prevalent growth factor in the central nervous system, how exposure to BDNF manifests at the network level remains unknown. Here we report that BDNF treatment affects rodent hippocampal network dynamics during development and recovery from glutamate-induced excitotoxicity in culture. Importantly, these effects are not obvious when traditional activity metrics are used, so we delve more deeply into network organization, functional analyses, and in silico simulations. We demonstrate that BDNF partially restores homeostasis by promoting recovery of weak and medium connections after injury. Imaging and computational analyses suggest these effects are caused by changes to inhibitory neurons and connections. From our in silico simulations, we find that BDNF remodels the network by indirectly strengthening weak excitatory synapses after injury. Ultimately, our findings may explain the difficulties encountered in preclinical and clinical trials with BDNF and also offer information for future trials to consider. |
| first_indexed | 2024-03-08T19:44:53Z |
| format | Article |
| id | doaj.art-e1e5c43717a04baca95775a9fd22f1ed |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-08T19:44:53Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-e1e5c43717a04baca95775a9fd22f1ed2023-12-24T12:26:43ZengNature PortfolioCommunications Biology2399-36422023-12-016112610.1038/s42003-023-05638-9Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitryKate M. O’Neill0Erin D. Anderson1Shoutik Mukherjee2Srinivasa Gandu3Sara A. McEwan4Anton Omelchenko5Ana R. Rodriguez6Wolfgang Losert7David F. Meaney8Behtash Babadi9Bonnie L. Firestein10Department of Cell Biology and Neuroscience, Rutgers UniversityDepartment of Bioengineering, University of PennsylvaniaDepartment of Electrical and Computer Engineering, University of MarylandDepartment of Cell Biology and Neuroscience, Rutgers UniversityDepartment of Cell Biology and Neuroscience, Rutgers UniversityDepartment of Cell Biology and Neuroscience, Rutgers UniversityDepartment of Cell Biology and Neuroscience, Rutgers UniversityDepartment of Physics, University of MarylandDepartment of Bioengineering, University of PennsylvaniaDepartment of Electrical and Computer Engineering, University of MarylandDepartment of Cell Biology and Neuroscience, Rutgers UniversityAbstract Plasticity and homeostatic mechanisms allow neural networks to maintain proper function while responding to physiological challenges. Despite previous work investigating morphological and synaptic effects of brain-derived neurotrophic factor (BDNF), the most prevalent growth factor in the central nervous system, how exposure to BDNF manifests at the network level remains unknown. Here we report that BDNF treatment affects rodent hippocampal network dynamics during development and recovery from glutamate-induced excitotoxicity in culture. Importantly, these effects are not obvious when traditional activity metrics are used, so we delve more deeply into network organization, functional analyses, and in silico simulations. We demonstrate that BDNF partially restores homeostasis by promoting recovery of weak and medium connections after injury. Imaging and computational analyses suggest these effects are caused by changes to inhibitory neurons and connections. From our in silico simulations, we find that BDNF remodels the network by indirectly strengthening weak excitatory synapses after injury. Ultimately, our findings may explain the difficulties encountered in preclinical and clinical trials with BDNF and also offer information for future trials to consider.https://doi.org/10.1038/s42003-023-05638-9 |
| spellingShingle | Kate M. O’Neill Erin D. Anderson Shoutik Mukherjee Srinivasa Gandu Sara A. McEwan Anton Omelchenko Ana R. Rodriguez Wolfgang Losert David F. Meaney Behtash Babadi Bonnie L. Firestein Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry Communications Biology |
| title | Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry |
| title_full | Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry |
| title_fullStr | Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry |
| title_full_unstemmed | Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry |
| title_short | Time-dependent homeostatic mechanisms underlie brain-derived neurotrophic factor action on neural circuitry |
| title_sort | time dependent homeostatic mechanisms underlie brain derived neurotrophic factor action on neural circuitry |
| url | https://doi.org/10.1038/s42003-023-05638-9 |
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