Brain pericyte calcium signaling during vasomotion and neurovascular coupling in murine models.

Abstract

Pericytes, which are mural cells located on the external surface of blood vessels in the brain, play a role in various processes such as vasomotion and neurovascular coupling (NVC), which control the flow of blood to the brain. These cells possess contractile abilities, but recent research has identified different types of pericytes with varying morphology and protein expression, leading to a debate regarding their functional roles in regulating cerebral blood flow (CBF). The objective of this study is to examine the impact of different pericyte types on vasomotion and NVC by investigating specific calcium channels that could generate intracellular calcium events and influence their capacity to constrict or dilate. By utilizing in vivo two-photon microscopy, we assessed the calcium signaling of distinct pericyte populations—ensheathing pericytes (EP) and capillary pericytes (CP)—in transgenic mice expressing genetically encoded calcium indicators (RCaMP1.07 and GCaMP6s). Concurrently, we measured the hemodynamic properties of nearby blood vessels. We also studied the effects of calcium channel blockers, namely nimodipine and Pyr3, on pericyte calcium signals and vessel hemodynamics. Our findings revealed differential impacts of specific calcium pathways in brain pericytes on local hemodynamic behavior. Nimodipine and Pyr3 reduced calcium activity in both pericyte types, and this reduction was different in distinct pericyte sub-cellular compartments (somata vs. processes). Nimodipine increased the diameter of vessels covered by EP, reduced their CBF and diminished the response to NVC. Likewise, nimodipine reduced CBF and NVC response of blood vessels covered by CP. Interestingly, Pyr3 caused vasodilation in both EP and CP, and it solely decreased the response to NVC in EP. Our data provide fresh insights into the mechanisms of calcium signaling in brain pericytes, shedding light on the role of these cells in regulating CBF. This knowledge holds potential for advancing our understanding of cerebrovascular and neurodegenerative diseases, where the full understanding of their development is yet to be determined.