Neurons are highly compartmentalized cells that require unique mechanisms for trafficking proteins and organelles to their specific compartments. Mitochondria are vital organelles that regulate the levels of ATP, calcium homeostasis and apoptosis. Many neurodegenerative diseases including ALS, Huntington's, Parkinson's and Alzhemier's show a disruption of mitochondrial transport in the axon suggesting that mitochondrial localization and function must be highly regulated for the neuron to function properly. This study will develop an in vivo method for the live imaging of sparsely labeled layer 2/3 cortical neurons via 2-photon microscopy. This method will then be used to quantitate mitochondrial dynamics and presynaptic capture along axons in vivo. The role of neuronal activity will also be interrogated to determine the effect it has on mitochondrial dynamics, presynaptic capture and function. Finally, this study will develop a method for the unbiased identification of proteins unique or abundant in axonal mitochondria as compared to somato-dendritic mitochondria. The results of this study will provide new insights into the in vivo mechanisms of mitochondrial dynamics and how activity regulates their presynaptic capture and function.

Public Health Relevance

Proper mitochondrial function is required for neuronal viability. Many neurodegenerative diseases including ALS, Huntington's, Parkinson's and Alzheimer's show a disruption of mitochondrial transport. Therefore, it is imperative to understand the dynamics of mitochondrial trafficking in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Career Transition Award (K99)
Project #
1K99NS091526-01
Application #
8869236
Study Section
NST-2 Subcommittee (NST)
Program Officer
Riddle, Robert D
Project Start
2015-07-15
Project End
2017-06-30
Budget Start
2015-07-15
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurosciences
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
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