High-resolution functional magnetic resonance imaging (fMRI) is an essential tool to non-invasively study human brain function. To fully utilize high-resolution fMRI application, it is crucial to establish the detailed cellular and signaling pathways for neurovascular coupling. Although our understanding of the signaling pathways has been significantly improved over the last few years, the pathways responsible for producing fMRI signal changes have not been fully clarified yet. The objective in this particular application is to determine the roles of astrocytes, a strong candidate as a neurovascular mediator, to high-resolution fMRI signal evoked by excitatory and inhibitory neuronal activity. To attain this objective, we will apply well-established multimodal techniques, including electrophysiology and fMRI, to the in vivo olfactory bulb model. The olfactory bulb is ideal to address neurovascular coupling issues since each bulb layer contains distinctive neuronal types and specific synapses, and individual layers can be preferentially activated unlike other brain regions. Our results are expected to contribute to the neural-specific interpretation of fMRI maps by revealing the roles of astrocytes in excitatory and inhibitory neuronal activity in sensory stimulation-evoked fMRI responses. Such findings should also provide insight into how neurovascular coupling is impaired in pathological conditions. Since astrocyte functions are impaired in certain diseases, defects in blood flow control may be caused by abnormal astrocyte function rather than from malfunction in neurons and vessels.

Public Health Relevance

The proposed research is relevant to public health because the establishment of the underlying physiological mechanisms of the functional MRI signal is expected to advance the diagnosis and treatment planning of diseases that are associated with disorders like stroke, hypertension, and Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
2R01EB003324-14
Application #
9175435
Study Section
Neuroscience and Ophthalmic Imaging Technologies Study Section (NOIT)
Program Officer
Liu, Guoying
Project Start
2000-12-01
Project End
2020-08-31
Budget Start
2016-09-08
Budget End
2017-08-31
Support Year
14
Fiscal Year
2016
Total Cost
$329,548
Indirect Cost
$104,548
Name
University of Pittsburgh
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Iordanova, Bistra; Vazquez, Alberto; Kozai, Takashi Dy et al. (2018) Optogenetic investigation of the variable neurovascular coupling along the interhemispheric circuits. J Cereb Blood Flow Metab 38:627-640
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Jin, Tao; Wang, Ping; Hitchens, T Kevin et al. (2017) Enhancing sensitivity of pH-weighted MRI with combination of amide and guanidyl CEST. Neuroimage 157:341-350
Lohani, S; Poplawsky, A J; Kim, S-G et al. (2017) Unexpected global impact of VTA dopamine neuron activation as measured by opto-fMRI. Mol Psychiatry 22:585-594
Poplawsky, Alexander John; Fukuda, Mitsuhiro; Kim, Seong-Gi (2017) Foundations of layer-specific fMRI and investigations of neurophysiological activity in the laminarized neocortex and olfactory bulb of animal models. Neuroimage :
Vasireddi, Anil K; Vazquez, Alberto L; Whitney, David E et al. (2016) Functional Connectivity of Resting Hemodynamic Signals in Submillimeter Orientation Columns of the Visual Cortex. Brain Connect :
Murphy, Matthew C; Poplawsky, Alexander J; Vazquez, Alberto L et al. (2016) Improved spatial accuracy of functional maps in the rat olfactory bulb using supervised machine learning approach. Neuroimage 137:1-8

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