Astrocytes are the predominate cell type in brain, closely associate with all other neural cell types, exhibit a wide array of neurotransmitter receptors, respond to neuronal activity, and release neuroactive molecules;in spite of this, we know very little about the role of these cells in physiology, behavior, or disease. A major limitation in this area is the lack of models that permit the study of astrocyte function in neural systems following sensory stimulation in living animals. To date, nearly all studies of astrocytic function have relied on pharmacological approaches to activate or inactivate signaling in these cells and to record the effects of their activity on surrounding cells in vitro or in situ. It is our view that progress in this area requires a model system where: 1) sensory input in living animals can be used to activate astrocytic signaling and, 2) behavioral readouts are available for determining the functional outcome of astrocytic signaling in vivo. To this end, we propose to use the mouse central visual pathway to investigate the role of astrocytic signaling cascades in synaptic transmission and plasticity as well as in vision.
In Specific Aim 1 we will use well-characterized slices of primary visual cortex to examine the pathways and mechanisms regulating astrocytic signaling in situ.
In Specific Aim 2 we will use in vivo imaging to determine if astrocytic calcium responses are spatially-restricted and important in the local control of vascular tone.
In Specific Aim 3 we will use in vivo imaging and genetically- modified mice to investigate the role of astrocytes in visual plasticity. Finally, in Specific Aim 4 we will genet- ically engineered mice to investigate the role of astrocytes in vision, a behavioral readout of sensory input into the visual cortex. Overall, the results of these studies should clarify the conditions where sensory input leads to the activation of astrocytic signaling and the role of astrocytic signaling in synaptic transmission and vision.

Public Health Relevance

Astrocytes are the predominate cell type in brain, closely associate with all other neural cell types, exhibit a wide array of neurotransmitter receptors, respond to neuronal activity, and release neuroactive molecules;in spite of this, we know very little about the role of these cells in physiology, behavior, or disease. Understanding the role that astrocytes play in the visual cortex could lead to new therapeutic treatments of visual disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY021190-02
Application #
8206491
Study Section
Cellular and Molecular Biology of Glia Study Section (CMBG)
Program Officer
Steinmetz, Michael A
Project Start
2011-01-01
Project End
2015-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$451,304
Indirect Cost
$144,613
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599