The oxygen initial dip in the brain of anesthetized and awake mice

Abstract

Significance Sensory stimulation generates a robust decrease in oxygen concentration (pO 2 initial dip) in brain tissue of anesthetized cats and rodents. This dip reports local activation of neurons much better than the delayed pO 2 increase associated with functional hyperemia. Here, we reinvestigated the issue in animals that recovered from acute surgery using two-photon lifetime microscopy. Targeting a distinct neuronal network that is the site of strong activation and energy consumption, we show that in anesthetized animals the pO 2 initial dip is present but extremely small in juxtasynaptic capillaries. In awake animals, it is no longer detectable in vessels or in the neuropil. This demonstrates that in healthy animals, neurovascular coupling is too fast and efficient to reveal a pO 2 initial dip.

Oxygen imaging of hypoxic pockets in the mouse cerebral cortex

“…Notably, the amplitude and the timing of BLI response differed between awake and KX-anesthetized mice (fig. S6), supporting the notion that anesthesia dampens tissue P o 2 and functional hyperemia dynamics ( 13 , 14 ).…”

Neurovascular coupling and briefCO2interrogate distinct vascular regulations

“…Here, we address the role of CO 2 produced by neuronal activation in generating NVC in layer 2/3 of the barrel cortex. All of our experiments were performed in chronic rather than acute preparations, as they preserve better brain metabolism 7 . We introduce briefCO 2 , a specific short and strong CO 2 stimulation that triggers sharp vascular and cellular responses in brain vessels and cells, and allows repetitive applications.…”

“…Initial measurements of partial pressure of oxygen (pO2) with Clark electrodes, performed in the brain parenchyma of anesthetized animals with acute craniotomies [3][4][5] , reported that sensory stimulation generated local pO2 dips, the timing of which was compatible with a triggering role in NVC 6 . This hypothesis was however recently questioned, as the pO2 dip disappeared in chronically-prepared awake mice, i.e., more akin to physiological conditions 7 . The triggering role of oxygen in NVC is therefore unlikely, even though one study reported that local application of O2 scavengers could generate a pO2 dip and an increase in blood flow 8 .…”

Electro-metabolic signaling

“…In the brain, state-of-the-art measurements of pO 2 have recently challenged the controversial view that hyperemia-induced increases in local pO 2 are preceded by an initial dip ( Kim et al, 2000 ; Logothetis, 2000 ; Buxton, 2001 ; Lindauer et al, 2001b ; Vanzetta and Grinvald, 2001 ; Thompson et al, 2003 , 2004 ; Kasischke et al, 2004 ; Dunn et al, 2005 ; Offenhauser et al, 2005 ; Sirotin et al, 2009 ; Hu and Yacoub, 2012 ; Ma et al, 2016 ; Aydin et al, 2022 ), which has been postulated to be driven by increased neuronal metabolism during activity. Instead, recent data support the view that O 2 tension is initially unchanged by the initiation of neuronal activity and is then followed by a large influx in O 2 during hyperemia ( Aydin et al, 2022 ).…”

“…In the brain, state-of-the-art measurements of pO 2 have recently challenged the controversial view that hyperemia-induced increases in local pO 2 are preceded by an initial dip ( Kim et al, 2000 ; Logothetis, 2000 ; Buxton, 2001 ; Lindauer et al, 2001b ; Vanzetta and Grinvald, 2001 ; Thompson et al, 2003 , 2004 ; Kasischke et al, 2004 ; Dunn et al, 2005 ; Offenhauser et al, 2005 ; Sirotin et al, 2009 ; Hu and Yacoub, 2012 ; Ma et al, 2016 ; Aydin et al, 2022 ), which has been postulated to be driven by increased neuronal metabolism during activity. Instead, recent data support the view that O 2 tension is initially unchanged by the initiation of neuronal activity and is then followed by a large influx in O 2 during hyperemia ( Aydin et al, 2022 ). Furthermore, classic positron-emission tomography experiments have convincingly demonstrated that activity-evoked increases in neuronal activity are not associated with significant increases in O 2 consumption but are accompanied by increased glucose utilization—leading to the hypothesis that aerobic glycolysis predominates as a mechanism to rapidly supply energy during sudden increases in brain activity ( Raichle and Mintun, 2006 ).…”