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Journal article
Regional Neurodegeneration in vitro: The Protective Role of Neural Activity
Frontiers in computational neuroscience, v 15, 580107
29 Mar 2021
PMID: 33854425
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Traumatic brain injury is a devastating public health problem, the eighth leading cause of death across the world. To improve our understanding of how injury at the cellular scale affects neural circuit function, we developed a protocol to precisely injure individual neurons within an in vitro neural network. We used high speed calcium imaging to estimate alterations in neural activity and connectivity that occur followed targeted microtrauma. Our studies show that mechanically injured neurons inactivate following microtrauma and eventually re-integrate into the network. Single neuron re-integration is dependent on its activity prior to injury and initial connections in the network: more active and integrated neurons are more resistant to microtrauma and more likely to re-integrate into the network. Micromechanical injury leads to neuronal death 6 h post-injury in a subset of both injured and uninjured neurons. Interestingly, neural activity and network participation after injury were associated with survival in linear discriminate analysis (77.3% correct prediction, Wilks' Lambda = 0.838). Based on this observation, we modulated neuronal activity to rescue neurons after microtrauma. Inhibition of neuronal activity provided much greater survivability than did activation of neurons (ANOVA, p < 0.01 with post-hoc Tukey HSD, p < 0.01). Rescue of neurons by blocking activity in the post-acute period is partially mediated by mitochondrial energetics, as we observed silencing neurons after micromechanical injury led to a significant reduction in mitochondrial calcium accumulation. Overall, the present study provides deeper insight into the propagation of injury within networks, demonstrating that together the initial activity, network structure, and post-injury activity levels contribute to the progressive changes in a neural circuit after mechanical trauma.
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Details
- Title
- Regional Neurodegeneration in vitro: The Protective Role of Neural Activity
- Creators
- Rosalind E. Mott - Cell Press, Cambridge, MA, United States.Catherine R. von Reyn - Drexel UniversityBonnie L. Firestein - Rutgers, The State University of New JerseyDavid F. Meaney (Corresponding Author) - University of Pennsylvania
- Publication Details
- Frontiers in computational neuroscience, v 15, 580107
- Publisher
- Frontiers Media Sa
- Number of pages
- 18
- Grant note
- Rutgers University Vice Chancellor for Research and Innovation Seed Fund Rutgers University Brain Health Institute Pilot Grant 12347 / Paul G. Allen Frontiers Group grant CBIR14IRG019; CBIR17IRG006; CBIR20IRG003 / New Jersey Commission on Brain Injury Research
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000639132400001
- Scopus ID
- 2-s2.0-85104037412
- Other Identifier
- 991019168585704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Mathematical & Computational Biology
- Neurosciences