Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Cell Rep. 2024 Apr 23;43(4):113970. doi: 10.1016/j.celrep.2024.113970. Epub 2024 Mar 19.
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.
为了满足大脑功能的高能量需求，脑血流（CBF）通过一种被称为神经血管耦合（NVC）的机制与神经元活动的变化平行。然而，哪些神经元在介导 NVC 中发挥作用尚不清楚。在这里，我们在小鼠和人类中鉴定出一种特定的皮质 GABA 能神经元群体，它们共同表达神经元型一氧化氮合酶和速激肽受体 1（Tacr1）。通过全组织清除，我们证明 Tacr1 神经元在功能连接的皮质区域之间延伸局部和长程投射。我们表明，胡须刺激通过前馈兴奋性通路在桶状皮层中引起 Tacr1 神经元的活动。此外，通过光遗传学实验，我们证明 Tacr1 神经元通过类似于胡须刺激的方式通过松弛壁细胞在介导 CBF 中起作用。最后，通过电子显微镜，我们观察到 Tacr1 过程接触星形胶质细胞终足。这些发现表明 Tacr1 神经元整合皮质活动来介导 NVC。
