Abstract

Axon regeneration is a fundamental and conserved property of nervous systems. But axon regeneration often fails to restore function after nerve injury. Thus, a key question in the field is to discover what determines the capacity of injured neurons to rebuild functional circuits. This proposal investigates new mechanisms that function in the injured neuron and that help determine whether or not effective regeneration occurs. The long-term goal is to gain a comprehensive understanding of the cellular functions that link neuronal injury to successful functional regeneration. The specific goal of this project is to analyze the process of synapse regeneration. The project uses a combination of in vivo approaches aimed at understanding how synapse regeneration works, why it fails to restore normal function, and how it can be improved. Completion of these Aims will describe fundamental cellular mechanisms that mediate functional axon regeneration after nerve injury.

Public Health Relevance

The proposed research investigates novel mechanisms in axon regeneration, a critical process that can restore function after nerve injury. Failure of neurons to regenerate and rebuild circuits after injury results in permanent functional loss and is a significant burden on public health. The research proposed here is expected to result in fundamental knowledge that suggests ways to promote functional recovery after nerve injury.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS094219-06
Application #
10211489
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Bambrick, Linda Louise
Project Start
2015-08-15
Project End
2026-02-28
Budget Start
2021-03-15
Budget End
2022-02-28
Support Year
6
Fiscal Year
2021
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Genetics
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Kurshan, Peri T; Merrill, Sean A; Dong, Yongming et al. (2018) ?-Neurexin and Frizzled Mediate Parallel Synapse Assembly Pathways Antagonized by Receptor Endocytosis. Neuron 100:150-166.e4
Byrne, Alexandra B; Hammarlund, Marc (2017) Axon regeneration in C. elegans: Worming our way to mechanisms of axon regeneration. Exp Neurol 287:300-309
Han, Sung Min; Baig, Huma S; Hammarlund, Marc (2016) Mitochondria Localize to Injured Axons to Support Regeneration. Neuron 92:1308-1323
Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi et al. (2016) Inhibiting poly(ADP-ribosylation) improves axon regeneration. Elife 5:
Wang, Xingxing; Sekine, Yuichi; Byrne, Alexandra B et al. (2016) Inhibition of Poly-ADP-Ribosylation Fails to Increase Axonal Regeneration or Improve Functional Recovery after Adult Mammalian CNS Injury. eNeuro 3: