The goal of this project is to quantify how natural behaviors modulate hemodynamic signals in the cortex, and to measure their coupling to neural activity. We will concurrently measure neural activity and hemodynamic signals, using electrophysiology, intrinsic optical signal imaging and two-photon laser scanning microscopy, in the cortex of awake, head-fixed mice. Mice will be free to alternate between running, grooming or quiescent behaviors on top of a spherical treadmill. We will use pharmacology to dissect the relative contributions of central neural and peripheral cardiovascular mechanisms in controlling cerebral blood flow. The neurovascular impulse response function, which defines the relationship between neural activity and blood flow, will be quantified across behaviors to test the constancy of neurovascular coupling. Lastly, we will test whether functional networks, areas with correlated blood flow during rest, are similarly correlated during locomotion. Understanding if, and how, the behavioral state modulates the cortical hemodynamic response, the coupling of blood flow to neural activity, and functional connectivity, are all critical for the interpretationof hemodynamic signals.
Changes in cerebral blood flow are coupled to neural activity, and are extensively used to assay brain activity non-invasively. This proposal seeks to understand how these blood flow changes are related to neural activity and behavioral state, which we hope will aid in the diagnosis and treatment of cerebrovascular and cognitive disorders.
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|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; 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|
|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|
|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; Drew, Patrick J (2014) Determination of vessel cross-sectional area by thresholding in Radon space. J Cereb Blood Flow Metab 34:1180-7|
|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|
|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:|