Relationship between oxygen consumption and neuronal activity in a defined neural circuit

Neuronal computations related to sensory and motor activity along with the maintenance of spike discharge, synaptic transmission, and associated housekeeping are energetically demanding. The most efficient metabolic process to provide large amounts of energy equivalents is oxidative phosphorylation and thus dependent on O₂ consumption. Therefore, O₂ levels in the brain are a critical parameter that influences neuronal function. Measurements of O₂ consumption have been used to estimate the cost of neuronal activity; however, exploring these metabolic relationships in vivo and under defined experimental conditions has been limited by technical challenges.

We used isolated preparations of Xenopus laevis tadpoles to perform a quantitative analysis of O₂ levels in the brain under in vivo-like conditions. We measured O₂ concentrations in the hindbrain in relation to the spike discharge of the superior oblique eye muscle-innervating trochlear nerve as proxy for central nervous activity. In air-saturated bath Ringer solution, O₂ levels in the fourth ventricle and adjacent, functionally intact hindbrain were close to zero. Inhibition of mitochondrial activity with potassium cyanide or fixation of the tissue with ethanol raised the ventricular O₂ concentration to bath levels, indicating that the brain tissue consumed the available O₂. Gradually increasing oxygenation of the Ringer solution caused a concurrent increase of ventricular O₂ concentrations. Blocking spike discharge with the local anesthetics tricaine methanesulfonate diminished the O₂ consumption by ~ 50%, illustrating the substantial O₂ amount related to neuronal activity. In contrast, episodes of spontaneous trochlear nerve spike bursts were accompanied by transient increases of the O₂ consumption with parameters that correlated with burst magnitude and duration.

Controlled experimental manipulations of both the O₂ level as well as the neuronal activity under in vivo-like conditions allowed to quantitatively relate spike discharge magnitudes in a particular neuronal circuitry with the O₂ consumption in this area. Moreover, the possibility to distinctly manipulate various functional parameters will yield more insight in the coupling between metabolic and neuronal activity. Thus, apart from providing quantitative empiric evidence for the link between physiologically relevant spontaneous spike discharge in the brain and O₂-dependent metabolism, isolated amphibian preparations are promising model systems to further dissociate the O₂ dynamics in relation to neuronal computations.