F4TGLUT · Food for thought: monitoring the effects of drugs and diet on neuronal glutamate release using nanoelectrodes

Glutamate is the primary activating neurotransmitter in the brain. It modulates synaptic plasticity of neurons, which underlies memory formation. However, it also plays a fundamental role in pathological processes, such as those related to Alzheimer’s disease. This essential role and future development of therapeutic agents urge the development of a highly-sensitive analytical method for determining glutamate levels at a cellular level. In this project I will create a miniaturized, in vitro system that will allow this. To develop it, my expertise in microfluidics and pharmacy will be supplemented by the host’s extensive experience with cell analysis and nanoelectrodes.When glutamate-type neurons in the brain are innervated, glutamate release into the synapse between adjacent neurons occurs. This triggers chemical signal transmission. Nanoelectrodes are uniquely equipped to monitor this neurotransmitter release with unprecedented spatiotemporal resolution. The combination with microfluidics will allow control of fluids and experiments at the nanoliter scale. Furthermore, through precisely fabricated microstructures, guidance of cell growth and precise placement of the nanoelectrodes in the device will be achieved.Glutamate modulates synaptic plasticity, a phenomenon understood to underlie memory formation. Furthermore, dietary compounds and drugs can influence glutamate neurotransmission. The proposed system enables selective exposure of individual neurons cultured in the microfluidic device to such compounds. Using the integrated nanoelectrodes, direct monitoring of their effects on chemical signaling between cells will be possible. The results will significantly contribute to our understanding of glutamate neurotransmission, and how drugs and diet can influence it. Additionally, the system combines cell culture, selective exposure and analyses at the cellular level using sensors and imaging, making it an ideal platform for future drug development research.