Activity-induced tissue oxygenation changes in rat cerebellar cortex: Interplay of postsynaptic activity and cerebral blood flow

Abstract

Neuronal activity, cerebral blood flow, and oxygen consumption are all strongly coupled, although the mechanisms behind remain unclear. We examined this coupling in rat cerebellar cortex by simultaneously recording local field potentials, tissue oxygen partial pressure (tpO2), and CBF using laser-Doppler flowmetry. Stimulation of the monosynaptic, excitatory climbing fiber system evoked activity-dependent increases in synaptic activity and blood flow, and biphasic tissue pO2 responses. Relating parameters of the initial negative tpO2 response to changes in synaptic activity revealed that the disappearance rate of oxygen in the tissue varied as a linear function of synaptic activity, while the area of the negative tpO2 response saturated at high levels of synaptic activity. Following the initial oxygen dip, tpO2 increased as a non-linear function of synaptic activity, paralleling the steep rise in blood flow at high levels of synaptic activity. Attenuation of the activity-dependent rise in blood flow by nNOS inhibition enlarged the negative tpO2 response and decreased the positive tpO2 response. These findings imply that the activity-induced reduction in tpO2 is counteracted by an increase in oxygen supply due to the rise in CBF. They also support the hypothesis that the positive tpO2 response is an overshoot caused by the evoked increase in CBF. Blockade of glutamatergic AMPA receptors with CNQX abolished synaptic activity, and CBF and tpO2 responses. We suggest, that in the cerebellum activity-dependent increaes in oxygen consumption can be recorded as the disapperance rate of oxygen in the tissue, and that oxygen consumption increases as a linear function of activity in postsynaptic cellular elements without evidence for a threshold. Our results provide new fundamental insights into the regulation of oxygen consumption during activation, showing direct coupling of activity in postsynaptic AMPA receptors to oxygen consumption.