Homeostatic signaling systems are believed to interface with the mechanisms of learning-related plasticity to achieve stable, yet flexible, neural function and animal behavior. The loss or disruption of homeostatic signaling is believed to participate in the cause or progression of many neurological diseases including autism spectrum disorders and epilepsy. Ultimately, clear links between homeostatic signaling and disease will require a detailed molecular understanding of homeostatic signaling systems. Here we identify several novel homeostatic plasticity genes that dramatically extend our understanding of how homeostatic signaling systems stabilize neural function.

Public Health Relevance

Homeostatic signaling systems are believed to interface with the mechanisms of learning-related neural plasticity to achieve stable, yet flexible, neural function and animal behavior. Recently, homeostatic signaling systems are being invoked as contributing to the cause or progression of diverse neurological diseases including Alzheimer's, epilepsy and autisms spectrum disorders. However, the molecular basis for the homeostatic regulation of neural function remains largely unknown. Ultimately, clear links between homeostatic signaling and disease will require a detailed molecular understanding of homeostatic signaling in the nervous system. We have a proven ability to identify new homeostatic signaling genes. Here we propose to characterize three novel, highly conserved homeostatic plasticity genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS039313-14
Application #
8438208
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Talley, Edmund M
Project Start
2000-02-01
Project End
2017-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
14
Fiscal Year
2013
Total Cost
$407,623
Indirect Cost
$132,653
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Müller, Martin; Genç, Özgür; Davis, Graeme W (2015) RIM-binding protein links synaptic homeostasis to the stabilization and replenishment of high release probability vesicles. Neuron 85:1056-69
Ford, Kevin J; Davis, Graeme W (2014) Archaerhodopsin voltage imaging: synaptic calcium and BK channels stabilize action potential repolarization at the Drosophila neuromuscular junction. J Neurosci 34:14517-25
Parrish, Jay Z; Kim, Charles C; Tang, Lamont et al. (2014) Krüppel mediates the selective rebalancing of ion channel expression. Neuron 82:537-44
Wang, Tingting; Hauswirth, Anna G; Tong, Amy et al. (2014) Endostatin is a trans-synaptic signal for homeostatic synaptic plasticity. Neuron 83:616-29
Davis, Graeme W (2013) Homeostatic signaling and the stabilization of neural function. Neuron 80:718-28
Younger, Meg A; Müller, Martin; Tong, Amy et al. (2013) A presynaptic ENaC channel drives homeostatic plasticity. Neuron 79:1183-96
Dickman, Dion K; Tong, Amy; Davis, Graeme W (2012) Snapin is critical for presynaptic homeostatic plasticity. J Neurosci 32:8716-24
Müller, Martin; Davis, Graeme W (2012) Transsynaptic control of presynaptic Ca²⁺ influx achieves homeostatic potentiation of neurotransmitter release. Curr Biol 22:1102-8
Muller, Martin; Liu, Karen Suk Yin; Sigrist, Stephan J et al. (2012) RIM controls homeostatic plasticity through modulation of the readily-releasable vesicle pool. J Neurosci 32:16574-85
Muller, Martin; Pym, Edward C G; Tong, Amy et al. (2011) Rab3-GAP controls the progression of synaptic homeostasis at a late stage of vesicle release. Neuron 69:749-62

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