(338d) Simulations of Electroenzymatic Glutamate Sensors in the Brain Reveal the Value of Finite Element Methods for Understanding Neurochemical Transmission
AIChE Annual Meeting
2021
2021 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Understanding the Rules of Life at the Micro- and Nano-Scale
Tuesday, November 9, 2021 - 1:24pm to 1:42pm
Simulations show that electroenzymatic glutamate sensor performance in vivo is complicated by both mass transfer resistances and clearance rates of glutamate (Glut) and H2O2 in the brain extracellular space, which is significantly different from the in vitro conditions where sensors are tested and calibrated. Through the use of 1-D model simulations, it is shown that sensor response in vivo has a much greater dependence on H2O2 mass transfer and clearance in the surrounding tissue than previously thought, potentially leading to sensor measurements more than double the expected value (based on prior sensor calibration in vitro) for glutamate release events close to the sensor surface. Sensor response in general is greatly affected by the distance between the sensor and location of glutamate release, with simulations showing that detection of glutamate released through neuronal signaling is limited to events within 30 µm of the sensor surface. Further simulations of more realistic neurotransmitter releases in 3 dimensions showed that excitation of thousands of synapses over the course of ~0.5 s is likely required for Glut detection; the magnitude of release required for detection suggests that even miniaturized sensors monitor the chemical activity of many neurons. Further modeling of chemical signaling processes in the brain with transport equations will be instrumental in the analysis of data collected by neurochemical sensors and in identifying the rates of fundamental neurochemical processes in various states of health, activity, and disease.