Microelectrode array studies of basal and potassium‐evoked release of l‐glutamate in the anesthetized rat brain

l‐glutamate (Glu) is the predominant excitatory neurotransmitter in the mammalian central nervous system. It plays major roles in normal neurophysiology and many brain disorders by binding to membrane‐bound Glu receptors. To overcome the spatial and temporal limitations encountered in previous in vivo extracellular Glu studies, we employed enzyme‐coated microelectrode arrays to measure both basal and potassium‐evoked release of Glu in the anesthetized rat brain. We also addressed the question of signal identity, which is the predominant criticism of these recording technologies. In vivo self‐referencing recordings demonstrated that our Glu signals were both enzyme‐ and voltage‐dependent, supporting the identity of l‐glutamate. In addition, basal Glu was actively regulated, tetrodotoxin (TTX)‐dependent, and measured in the low micromolar range (approximately 2 µm) using multiple self‐referencing subtraction approaches for identification of Glu. Moreover, potassium‐evoked Glu release exhibited fast kinetics that were concentration‐dependent and reproducible. These data support the hypothesis that Glu release is highly regulated, requiring detection technologies that must be very close to the synapse and measure on a second‐by‐second basis to best characterize the dynamics of the Glu system.