Changes in neural activity drive changes in local blood flow in the brain. These changes in cerebral hemodynamics are important for maintaining normal brain health, and are used for non-invasively inferring neural activity. However, hemodynamic signals can decouple from local neural activity, making the understanding of the mechanism of this decoupling critical for interpreting and decoding hemodynamic signals. We hypothesize that hemodynamic signals in a given brain area are controlled by both vasodilatory signals released by local neurons, and by vasoconstrictory neuromodulation, specifically noradrenaline, both of which will vary with behavioral state, such locomotion. We will mechanistically test this hypothesis using optical imaging (intrinsic optical signal imaging and 2-photon microscopy), local pharmacological infusions, chemogenetics, oxygen polarography, and electrophysiology in awake mice. These experiments will elucidate how noradrenergic modulation, which is involved in alertness and attention, interacts with local neural activity to generate changes in blood flow and oxygenation. The end result of these experiments will be a unified understanding of how neural activity and neuromodulation control hemodynamic signals during behavior. 1

Public Health Relevance

Cerebral blood flow is controlled by local neural activity and global neuromodulatory state. This proposal will determine how neural activity and neuromodulation combine to generate changes in hemodynamic signals and oxygenation, allowing a more accurate interpretation of hemodynamic signals. 1

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS078168-06
Application #
9661323
Study Section
Mechanisms of Sensory, Perceptual, and Cognitive Processes Study Section (SPC)
Program Officer
Babcock, Debra J
Project Start
2013-03-01
Project End
2024-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
Adams, Matthew D; Winder, Aaron T; Blinder, Pablo et al. (2018) The pial vasculature of the mouse develops according to a sensory-independent program. Sci Rep 8:9860
Winder, Aaron T; Echagarruga, Christina; Zhang, Qingguang et al. (2017) Weak correlations between hemodynamic signals and ongoing neural activity during the resting state. Nat Neurosci 20:1761-1769
Gao, Yu-Rong; Ma, Yuncong; Zhang, Qingguang et al. (2017) Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal. Neuroimage 153:382-398
Gao, Yu-Rong; Drew, Patrick J (2016) Effects of Voluntary Locomotion and Calcitonin Gene-Related Peptide on the Dynamics of Single Dural Vessels in Awake Mice. J Neurosci 36:2503-16
Shirey, Michael J; Smith, Jared B; Kudlik, D'Anne E et al. (2015) Brief anesthesia, but not voluntary locomotion, significantly alters cortical temperature. J Neurophysiol 114:309-22
Gao, Yu-Rong; Greene, Stephanie E; Drew, Patrick J (2015) Mechanical restriction of intracortical vessel dilation by brain tissue sculpts the hemodynamic response. Neuroimage 115:162-76
Huo, Bing-Xing; Gao, Yu-Rong; Drew, Patrick J (2015) Quantitative separation of arterial and venous cerebral blood volume increases during voluntary locomotion. Neuroimage 105:369-79
Huo, Bing-Xing; Greene, Stephanie E; Drew, Patrick J (2015) Venous cerebral blood volume increase during voluntary locomotion reflects cardiovascular changes. Neuroimage 118:301-12
Letourneur, Annelise; Chen, Victoria; Waterman, Gar et al. (2014) A method for longitudinal, transcranial imaging of blood flow and remodeling of the cerebral vasculature in postnatal mice. Physiol Rep 2:
Huo, Bing-Xing; Smith, Jared B; Drew, Patrick J (2014) Neurovascular coupling and decoupling in the cortex during voluntary locomotion. J Neurosci 34:10975-81

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