Hemodynamic changes are encoded into distinct astrocyte and neuronal responses highlighting the importance of bidirectional communication at the neurovascular unit

Abstract

To gain insights into the dynamic signaling events at the neurovascular unit, we evaluated if hemodynamic changes within parenchymal arterioles altered glial and/or neuronal activity in cortical brain slices. We hypothesize that astrocytes monitor brain hemodynamics and that changes in pressure and/or flow are rapidly sensed by these cells and tranduced to neighboring neurons adjusting, in this way, activity to blood flow supply. We used a novel in vitro approach which included pressure/flow changes in parenchymal arterioles while simultaneously measuring Ca2+ activity in perivascular astrocytes and firing activity from pyramidal or cortical interneurons. Our findings show that astrocytes rapidly sense increases in pressure (from 40 to 80 mmHg) resulting in a 124% increased in Ca2+ oscillation frequency. Moreover, an 80% reduction in neuronal firing activity was observed in the presence of the hymodynamic stimulus. A detailed characterization of astrocytic responses revealed the presence of multiple response patterns to the hemodynamic stimulus including: transient activation (21%), tonic/oscillatory activity (26%) and inhibition (52%). The present study support a complex form of vascular‐to‐glial‐to‐neuronal communication in which hemodynamic changes are encoded into distinct astrocyte/neuronal responses.