Effects of Glutamate Receptor Activation on Local Oxygen Changes

Glutamate is ubiquitous throughout the brain and serves as the primary excitatory neurotransmitter. Neurons require energy to fire, and energetic substrates (i.e., O₂, glucose) are renewed via cerebral blood flow (CBF) to maintain metabolic homeostasis. Magnetic resonance brain functionality studies rely on the assumption that CBF and neuronal activity are coupled consistently throughout the brain; however, the origin of neuronal activity does not always coincide with signals indicative of energy consumption (e.g., O₂ decreases) at high spatial resolutions. Therefore, relationships between excitatory neurotransmission and energy use must be evaluated at higher resolutions. In this study, we showed that both endogenously released and exogenously ejected glutamate decrease local tissue O₂ concentrations, but whether hyperemic O₂ restoration followed depended on the stimulus method. Electrically stimulating the glutamatergic corticostriatal pathway evoked biphasic O₂ responses at striatal terminals: first O₂ decreased, then concentrations increased above baseline. Using iontophoresis to locally eject ionotropic glutamate receptor antagonists revealed that these receptors only influenced the O₂ decrease. We compared electrical stimulation to iontophoretic glutamate stimulation, and measured concurrent single-unit activity and O₂ to limit both stimulation and recordings to <50 μm radius from our sensor. Similarly, iontophoretic glutamate delivery elicited monophasic O₂ decreases without subsequent increases.