A balance of excitatory (E) and inhibitory (I) electrical signaling in local networks (E/I ratio) is observed in awake states and in sleep, with the exception of slow-wave sleep in humans and monkeys 7. Two important and ubiquitous neurotransmitters in the brain are l-glutamine (GLU) and γ-aminobutyric acid (GABA), which are the major excitatory and inhibitory neurotransmitters, respectively. Near real-time measurement of neurotransmitter levels in the brain is expected to reveal important clues to the underlying mechanisms of neurological disorders, such as epilepsy, addiction, motor control 1– 3, and secondary damage after stroke 4 and traumatic brain injury 5, 6. Additionally, we recorded from a freely moving rat over fourteen weeks, inserting fresh biosensors each time, thus demonstrating that the microwire biosensor overcomes the time limitation of permanently implanted biosensors and that the biosensors detect relevant changes in GLU and GABA levels that are consistent with various behaviors. We measured real-time dynamics of GLU and GABA in rat hippocampal slices and observed a significant, nonlinear shift in the E/I ratio from excitatory to inhibitory dominance as electrical stimulation frequency increased from 10 to 140 Hz, suggesting that GABA release is a component of a homeostatic mechanism in the hippocampus to prevent excitotoxic damage. In addition, the microwire biosensors were in the same geometric plane for the improved acquisition of signals in planar tissue including rodent brain slices, cultured cells, and brain regions with laminar structure. Biosensor coatings were based on our previously developed GLU and reagent-free GABA shank-type biosensor. To overcome the time limitation of permanently implanted microbiosensors, we created a microwire-based biosensor that can be periodically inserted into a permanently implanted cannula. Enzyme-based microelectrode array biosensors present the potential for improved biocompatibility, localized sample volumes, and much faster sampling rates over existing measurement methods. Dysregulation of the E/I ratio is associated with numerous neurological disorders.
Glutamate (GLU) and γ-aminobutyric acid (GABA) are the major excitatory (E) and inhibitory (I) neurotransmitters in the brain, respectively.
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