Michael HeienAssistant Professor
Building: CSML 220
Education and Appointments
Chemical measurements of synapse formation
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.
Omiatek DM, Dong Y, Heien ML, Ewing AG. Only a Fraction of Quantal Content is Released During Exocytosis as Revealed by Electrochemical Cytometry of Vesicles. ACS Chemical Neuroscience. 2010 1, 234-245. doi: 10.1021/cn900040e
Makos MA, Kim YC, Han KA, Heien ML, Ewing AG. Using in vivo electrochemistry to study the physiological effects of cocaine and other stimulants on the Drosophila melanogaster dopamine transporter. ACS Chemical Neuroscience. 2010 1, 74-83. doi: 10.1021/cn900017w
Piehowski PD, Davey AM, Kurczy ME, Sheets ED, Winograd N, Ewing AG, Heien ML. ToF-SIMS imaging of sub-cellular lipid heterogeneity: Poisson counting and spatial resolution. Analytical Chemistry. 2009 81(14), 5593-5602. doi: 10.1021/ac901065s
Zhang B, Adams KL, Luber SJ, Eves DJ, Heien ML, Ewing AG. Spatially and temporally resolved single-cell exocytosis utilizing individually addressable carbon microelectrode arrays. Analytical Chemistry. 2008 80(5), 1394-1400. doi: 10.1021/ac702409s
Heien, ML, Khan AS, Ariansen JL, Cheer JF, Phillips PEM, Wassum KM, Wightman RM. Real-time measurement of dopamine fluctuations after cocaine in the brain of behaving rats. Proceedings of the National Academy of Sciences USA. 2005 102(29) 10023-10028. doi: 10.1073/pnas.0504657102