Cellular Interrogation of Neurovascular Coupling: The Role of Cortical Inhibitory Interneurons

Neurovascular coupling (NVC) ensures that cerebral blood flow (CBF) is precisely matched to local neuronal activity, supporting the brain’s high metabolic demand. While excitatory neurons have long been the focus of NVC research, inhibitory cortical interneurons (INs) have emerged as important, and underexplored, contributors to the regulation of cerebral haemodynamics. This thesis investigates the cellular mechanisms through which two populations of INs, somatostatin-expressing (SST) and neuronal nitric oxide synthase-expressing (nNOS), contribute to NVC, using a cell-type-specific optogenetic stimulation with high-resolution measurements of vascular and neuronal responses, and pharmacological agents.
I demonstrated that both SST and nNOS-IN activation drive an increase in cerebral blood volume (CBV), and that while the nNOS-IN driven increase in CBV was dependent on nitric oxide (NO), the initial sensory-evoked NVC response was not.
Together, these studies provide novel insights into the contributions of subpopulations of INs to NVC, highlighting the diversity of mechanisms by which they influence cerebrovascular dynamics. These findings advance our understanding of the neurovascular unit and lay the groundwork for more precise models of NVC in health and disease.