Regional and developmental differences in neurovascular coupling
Open Access
- Author:
- Gheres, Kyle
- Graduate Program:
- Molecular, Cellular, and Integrative Biosciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 29, 2021
- Committee Members:
- Patrick Drew, Chair & Major Field Represnt
Timothy Jegla, Committee Member & Major Field Represnt
Kevin Alloway, Committee Member & Major Field Represnt
Nanyin Zhang, Committee Member & Related Areas Repres
Santhosh Girirajan, Committee Member & Major Field Represnt
Melissa Rolls, Program Head/Chair - Keywords:
- Neurovascular Coupling
Blood Flow
Development - Abstract:
- In adult mammals, behavior evokes increased neural activity and blood volume in somatosensory cortex. This neurovascular coupling supplies active neurons with metabolites to sustain cognitive processes and is the underlying relationship used to infer neural activity from non-invasive imaging techniques such as fMRI. Canonically, changes in blood volume are driven through locally generated signaling mechanisms that are dependent on neural activity. However, previous studies have shown some brain regions have inverted or absent neurovascular coupling, and neurovascular coupling seems to be inverted in very young animals and humans. For my thesis, I investigated the mechanisms underlying the region- and age-dependence of neurovascular coupling. Previous experiments have identified nitric oxide (NO) as an important mediator of neurovascular coupling in somatosensory cortex. However, behavior evoked physiology of NO producing interneurons has never been recorded in vivo. I tested whether the activity of NO producing interneurons in somatosensory cortex increased during behavior and whether this activity was reflective of the local neural population. I then confirmed previous studies’ observations that locomotion fails to increase blood volume in frontal cortex and investigated whether the lack of behavior-evoked neurovascular coupling could be explained by differences in NO producing interneuron activity. Using fiber photometry to record intensity changes of genetically encoded calcium indicator GCaMP6s, I was able to demonstrate that locomotion increases intracellular calcium levels in NO producing neurons similar to nearby glutamatergic neurons in both somatosensory and frontal cortices. I additionally found that facial grooming evokes similar increases in neural activity and vasodilation in frontal cortex demonstrating behavior dependent neurovascular coupling in the region. These results show that NO producing neurons are modulated in a similar behavior evoked manner as other nearby neurons and that their increases alone are not sufficient to evoke vasodilation in frontal cortex. While functional neuroimaging studies have been used across the life span of mammalian subjects, previous experiments have called in to question the how accurately blood volume reflects local neural activity in the juvenile stage of life. I used head-fixed mice, optical imaging and in vivo electrophysiology to investigate how the whisker stimulus evoked hemodynamic response develops over the juvenile period. I then investigated how arousal state changes associated with the sleep wake cycle effect cortical blood volume and shape stimulus evoked hemodynamics. I was able to demonstrate that stimulus evoked hemodynamics are absent prior to eye opening and increase in amplitude during the third postnatal week. I then show that juvenile animals rapidly transition between sleep and wake states with significant increases in blood volume occurring during sleep and decreases upon awakening.