Glutamate (Glu), a major excitatory neurotransmitter in brain, plays many critical roles in brain functions including learning, memory formation, and mood control. Furthermore, abnormalities in glutamatergic signaling is implicated in various neurological disorders such as epileptic seizure. Although Glu is primarily transmitted synaptically, recent findings reveal that extra-synaptic Glu transmission, due to its 'spillover' from the synaptic cleft and reaching to other cells in the vicinity through bulk diffusion, plays a greater role in the overall glutamatergic signaling than previously had been acknowledged. Therefore, accurate monitoring of extra-synaptic Glu with high spatial and temporal resolution is critical in understanding the mechanisms of bulk Glu spillover and how it impacts our brain health. Currently, there are limitations in the technology to reliably track the spatiotemporal dynamics of extra-synaptic Glu transmission with the needed resolution. The overall objective of this project is to demonstrate the feasibility of monitoring extracellular Glu continuously in real-time from mice brain slices using the proposed Glu sensor. The Pl has been developing an innovative polymer-based Glu receptor that can be used to create a rapid responsive and microscale electrochemical sensor. Preliminary data shows that the sensor is chemically selective to Glu and exhibits time resolution of a few seconds.
