INCREASED NOREPINEPHRINE LEVELS IMPAIR NEUROVASCULAR COUPLING RESPONSES DURING ACTIVE SENSING

Neurovascular coupling (NVC) ensures sufficient and targeted blood flow during increased neuronal activity. While the phenomenon of neurovascular coupling is well-established, the role of norepinephrine (NE) in NVC remains elusive. The variable levels of NE depend on arousal and thus the emotional context in which NVC responses occur. We used 2-photon microscopy to measure astrocytic Ca2+ levels and blood vessel dynamics in the whisker barrel cortex of awake head-fixed animals. We employed the selective NE reuptake inhibitor (NRI) reboxetine to elevate NE levels by blocking the norepinephrine transporter (NET). Furthermore, considering the astrocyte sensitivity to NE and their role in the tripartite synapse, we utilized astrocytic Gi-DREADD (hM4Di) expression to selectively modify astrocytic calcium signaling in barrel cortex. We demonstrate that in-vivo elevation of NE levels significantly attenuates the dilation of both penetrating arteries and capillaries associated with volitional whisking activity. Notably, this inhibitory effect of NE reuptake blockade was not observed when the whisker deflections were experimentally evoked. Our findings reveal that NVC during active sensing is highly sensitive to the homeostatic balance of norepinephrine. Moreover, NE and astrocytic Ca2+ pathways interact to gate metabolic support in the somatosensory cortex. These results reveal that the level of arousal influence the metabolic supply during active sensing.