[notice]The most recent Heien Lab poster can be found here.[/notice]
Where two neurons meet, they can form a chemical synapse, a site where information is propagated from one neuron to the next. These regions are specialized to allow rapid (millisecond) communication. In response to an electrical impulse, the terminal of a presynaptic neuron releases neurotransmitters, which diffuse across the synaptic cleft to activate specific receptors on the postsynaptic neuron. These receptors cause an electrical discharge in the postsynaptic cell, thereby propagating the electrical signal. The formation and pruning of new synapses is a method the brain has for changing its architecture. For rapid communication, the presynaptic and postsynaptic elements of the synapse must be aligned, such that neurotransmitter release occurs at sites opposite receptors in the postsynaptic membrane. One assumption is that this alignment is achieved by adhesion molecules – specific cell-surface proteins located on both sides of the synapse that grip each other across the synaptic cleft and hold the presynaptic and postsynaptic apparatus in place. The synapse is central to processing of information and communication between neurons, and molecular imaging of the synapse can offer insight into the nature of the synapse and its formation.
- What molecules are involved in synapse formation?
- Once formed, what molecules maintain the structure of the synapse?
- In order to form synapses, this membrane region needs to be functionalized. What is the role of lipids in the formation of chemical synapses?
- How does this affect the neurotransmitter released?
Both electrochemical and mass spectrometric methods provide information regarding the chemical identity and concentration of molecules. These methods can also be combined with complimentary techniques such as electrophysiology and fluorescence imaging to provide insights into fundamental process at the cellular level. This research has the potential to have significant impact as these molecules can be used as pharmacological targets in various cognitive and psychiatric disorders and diseases.
Current Projects in the Heien Laboratory:
Polymer Micro and Nano Electrodes:
Richard’s project in my lab is the development of polymer electrodes for the detection of transmitter molecules like dopamine, norepinephrine, and seratonin in a variety of instrumental setups. This project is a collaboration with Dr. Rafael Taboryski at the Technical University of Denmark. These see application as end-column detectors for capillary electrophoresis or other separation techniques. Poly-ethylenedioxythiophene (PEDOT) is an optically transparent conductive polymer (represented in black in the image below). We have been using vapor-phase polymer synthesis techniques as well as photolithography to construct electrodes from PEDOT, and they have now been characterized electrochemically for the detection of several neurotransmitters. These electrodes are inexpensive, easy to fabricate in large quantities, and have reproducible electrochemical behavior. A current area of work with these electrodes is in performing high-speed transmitter detection using fast-scan cyclic voltammetry to resolve different transmitter molecules in solution.
Electrochemical detection of individual liposomes using a novel hybrid device:
Nick is focused on the development and high sensitivity electrochemical detectors for use in analytical separation and electrochemical cytometry. Capillary zone electrophoresis and micellar electrokinetic chromatography are utilized for the separation of trace amount of small molecule neurotransmitters. Conducting polymer electrodes composed of poly(3,4-ethylenedioxythiophene) or PEDOT are utilized as a new type of electrochemical detector that is easily interfaced with microfluidic systems. Individual lipid vesicles which encapsulate small amounts of drug or neurotransmitter compounds are studied on an individual basis using electrochemical cytometry which enables amperometric detection of zeptomoles of material encapsulated within each nanometer scale vesicle. Because lipid vesicles are both an excellent model system for synaptic vesicles and are finding an increasing role in therapeutics for diseases such as metastic breast cancer the study of these nanoparticle systems promises new insight into neuroscience and drug development.
Delayed timing fast scan cyclic voltammetry:
Chris’ project is pushing the detection limits of cyclic voltammetry for neurotransmitters. Background-subtracted fast-scan cyclic voltammetry at carbon-fiber microelectrodes is an excellent tool for monitoring real time neuronal chemical communication. We are currently working on a new software suite that has been designed to improve both data collection and analysis of experiments using fast-scan cyclic voltammetry. Additionally we are working on a project that combines a single electrode and a relay to switch between two waveforms at a on a microsecond timescale, which allows us to perform two types of experiments. The first is the determination of the equilibrium constant and kinetics of adsorption for neurotransmitters like serotonin and dopamine. The second experiment involves modifying the applied waveform, making it possible to determine tonic concentrations in situ, laying the foundation for experiments to determine the basal concentration of several analytes in vivo. Lastly we combine the experimental data with that predicted by models we have designed in Comsol Multiphysics® 4.0.