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Tacr1 marks a population of long-range inhibitory neurons that regulate neurovascular coupling

Ruff, Catherine (2021) Tacr1 marks a population of long-range inhibitory neurons that regulate neurovascular coupling. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The brain is a metabolically expensive organ consuming 20% of the body’s energy at rest yet lacks energy reserves. To meet the high energy demands of active neurons blood flow parallels changes in brain activity by a mechanism known as neurovascular coupling (NVC). Although this mechanism is critical to normal brain function and the basis of functional brain imaging, a standard modality for measuring neural activity in health and disease, NVC is incredibly complex and the process remains poorly understood. Here, we identify a unique population of cortical GABAergic that express a G-protein coupled receptor, tachykinin receptor 1 (Tacr1), in mouse and humans. Whole-tissue clearing experiments reveal that these Tacr1 neurons extend local and long-range projections across functionally connected cortical regions. Through two-photon microscopy and calcium imaging, we show that whisker stimulation drives activity in Tacr1 neurons in the barrel cortex. Tacr1 neurons receive direct excitatory drive from both glutamatergic thalamocortical and corticocortical neurons shown by subcellular ChR2-assisted circuit mapping. Optogenetic activation of Tacr1 neurons in vivo is sufficient for vasodilation, whereas ArchT-mediated inhibition of these cells significantly reduces the whisker-evoked hemodynamic response. Furthermore, vasodilation mediated by Tacr1 neurons is initiated by capillary pericytes. Finally, by electron microscopy we see that Tacr1 presynaptic terminals and postsynaptic densities contact astrocytes. These findings identify a neural correlate that integrates cortical activity to modulate cerebral blood flow.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ruff, Catherinecar147@pitt.educar147
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorRoss, Sarahsaross@pitt.edusaross
Committee ChairVazquez, Albertoalv15@pitt.edualv15
Committee MemberFish, KennethKennethFish@pitt.eduKennethFish
Committee MemberHooks, Bryanhooksm@pitt.eduhooksm
Committee MemberRunyan, Carolinerunyan@pitt.edurunyan
Date: 15 September 2021
Date Type: Publication
Defense Date: 30 March 2021
Approval Date: 15 September 2021
Submission Date: 11 May 2021
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 74
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: neurovascular coupling, cerebral blood flow, tachykinin receptor 1, inhibitory neurons, pericytes
Date Deposited: 16 Sep 2021 01:39
Last Modified: 16 Sep 2021 01:39
URI: http://d-scholarship.pitt.edu/id/eprint/41066

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