Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
Fernanda Juarez Anaya
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
Samuel J. Dienel
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Adiya Rakymzhan
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
Alain Altamirano-Espinoza
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
Jay Couey
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
Mitsuhiro Fukuda
Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA
Alan M. Watson
Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA, USA
Aihua Su
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
Kenneth N. Fish
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Maria E. Rubio
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
Bryan M. Hooks
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
Sarah E. Ross
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA; Corresponding author
Alberto L. Vazquez
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA; Corresponding author
Summary: To meet the high energy demands of brain function, cerebral blood flow (CBF) parallels changes in neuronal activity by a mechanism known as neurovascular coupling (NVC). However, which neurons play a role in mediating NVC is not well understood. Here, we identify in mice and humans a specific population of cortical GABAergic neurons that co-express neuronal nitric oxide synthase and tachykinin receptor 1 (Tacr1). Through whole-tissue clearing, we demonstrate that Tacr1 neurons extend local and long-range projections across functionally connected cortical areas. We show that whisker stimulation elicited Tacr1 neuron activity in the barrel cortex through feedforward excitatory pathways. Additionally, through optogenetic experiments, we demonstrate that Tacr1 neurons are instrumental in mediating CBF through the relaxation of mural cells in a similar fashion to whisker stimulation. Finally, by electron microscopy, we observe that Tacr1 processes contact astrocytic endfeet. These findings suggest that Tacr1 neurons integrate cortical activity to mediate NVC.
