Basic Research – Chemistry

Most neuromodulators signal, at least in part, by volume transmission. That is, the signaling molecules are released at sites where there is no synapse, and/or they escape from synapses to diffuse through the tissue more widely. This diffusion through the extracellular space (ECS), away from sites of release is not well understood. Furthermore, it complicates using pre-synaptic activity in modulatory axons as a measure of modulatory signaling.

To address this complexity, we collaborate with computational and theoretical neuroscientists to develop models of ECS diffusion and modulator concentration, and then test those models using methods from neurochemistry.

In this branch of the lab, we currently make use of the following methods:

• Fast scan cyclic voltammetry and constant potential amperometry to measure levels of individual modulatory molecules in the ECS.
• Microdialysis to sample the ECS
• Liquid chromatography combined with electrochemical detection or mass spectrometry to quantify levels of multiple modulators from single samples

This is also the branch of the lab in which we currently do most of our new methods development. We are working on:

• Improved electrochemical electrodes for use in vivo
• Applying methods from proteomics and metabolomics to the study of neuromodulation
• Detecting neuropeptides
• Optical sensors
• Improving viral methods for cell access