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Bi‐directional neurovascular communication in the brain

We previously showed that changes in the resting tone of intracortical arterioles results in opposite‐type vascular responses (dilations and constrictions). Such findings also suggest that in addition to the well‐studied flow of information characteristic of functional hyperemia, namely neuron‐to‐astrocyte‐to‐arteriole, stimulation in a reverse manner may uncover yet another important function associated to brain information processing and/or neuroprotection. Here we show that three different modes of stimulation (depolarization, endothelin‐1 and mechanical) which induced pial arteriolar constriction subsequently increased intracellular calcium in cortical astrocytes (P<0.0001, n=5). A potential mechanism leading to this event is the activation of mechanosensitive TRPV4 channels expressed in astrocytic endfeet processes. Attesting to the presence of these channels, bath applied 4 alpha‐phorbol 12,13‐didecanoate significantly (P<0.0001) increased calcium oscillations in astrocytes (0.008±0.002 to 0.026±0.004 Hz, n=4) with prominent changes occurring in perivascular processes. We propose that stretching of astrocytic endfeet membranes, following vessel diameter changes, unveils an important mode of communication between the vasculature and the brain. Ongoing studies aim to address whether neuronal and glial activity is indeed regulated by changes in blood flow.