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We are principally interested in mechanisms of short-term synaptic plasticity and the impact of that plasticity on function in the nervous system.

For our research we use two model vertebrate systems. A simple vertebrate model that affords us some fundamental advantages in this research is the lamprey central nervous system. The lamprey has a central nervous system that is very simple for a vertebrate and which may be kept alive, isolated but otherwise intact, for a number of days. Additionally, a group of axons in the spinal cord are very large and contain presynaptic structures that are exceptionally accessible to the experimentalist. This combination of features enables us to investigate synaptic plasticity at great detail and to determine its role in motor control. We have focused on the means by which G protein coupled receptors mediate enhancement and inhibition of glutamate release. We have identified a direct target for Gbg on the SNARE complex, the machinery for fusion of synaptic vesicles

More recently we have utilized the rat hippocampus to determine whether similar mechanisms of synaptic plasticity are present in the mammalian brain. We have begun to focus on the role of kinase activation and short-term modification of transmitter release, in addition to how these modifications can alter the formation of memory during induction phases of long-term plasticity.

The movie shows a 3 dimensional reconstruction of a fluorescently labeled pair of neurons recorded simultaneously in the spinal cord of the lamprey. The presynaptic terminal is labeled in green with fluorescently tagged phalloidin injected through a microelectrode in to the axon. Phalloidin is a toxin that binds to actin and thus labels synaptic vesicle clusters. The post synaptic neuron is labeled with a red fluorescent dye that was contained in the patch clamp electrode used to record from the cell. The large jet-like red object is the image of this recording electrode.

The cell clearly makes contact with synaptic zones on the axon with spine-like projections.

Some Relevant Publications

Blackmer T, Larsen EC, Bartleson C, Kowalchyk JA, Yoon E-J, Preininger AM, Alford S, Hamm HE, Martin TFJ. (2005) G protein βγ directly regulates SNARE protein fusion machinery for secretory granule exocytosis. Nature Neuroscience 8: 421-425 pubmed

Gerachshenko T, Blackmer T, Yoon EJ, Bartleson C, Hamm HE, Alford S. (2005) Gβγ acts at the C terminus of SNAP-25 to mediate presynaptic inhibition. Nature Neuroscience 8: 597-605. pubmed

Photowala H, Freed R, Alford S. (2005) Location and function of vesicle clusters, active zones and Ca2+ channels in the lamprey presynaptic terminal. J Physiol. 2005 569:119-135. pubmed

Photowala H, Blackmer T, Schwartz E, Hamm HE, Alford S (2006) G protein βγ-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties.Proc Natl Acad Sci U S A. 103:4281-4286. pubmed

Smetana RW, Alford S, Dubuc R (2007) Muscarinic receptor activation elicits sustained recurring depolarizations in reticulospinal neurons. J Neurophysiol. 97:3181-3192 pubmed

Schwartz EJ, Blackmer T, Gerachshenko T, Alford S. (2007) Presynaptic G protein-coupled receptors regulate synaptic cleft glutamate via transient vesicle fusion. J. Neuroscience 27:5857-5868 pubmed

YoonYoon E-J, Gerachshenko T, Spiegelberg BD, Alford S, & Hamm HE. (2007) Gβγ regulates exocytosis by interfering with Ca2+-dependent binding of synaptotagmin to the SNARE complex. Molecular Pharmacology 72:1210-1219 pubmed

Gerachshenko T, Schwartz E, Bleckert A, Photowala H, Seymour A and Alford S (2009) Presynaptic G protein-coupled receptors dynamically modify vesicle fusion, synaptic cleft glutamate concentrations and motor behavior. Journal of Neuroscience 29(33):10221-33. pubmed

 

Neuroscience is an area of study and research that is rapidly expanding at the national and local levels. The University is actively involved in teaching and research in the Neurosciences at Undergraduate and Graduate levels.

Undegraduate students may chose to major in Neuroscience in a joint program between the departments of Biology, Psychology, Chemistry and Philosophy. This program is coordinated through the Laboratory in Neurobiology.

At the Graduate level, Neuroscience education is coordinated through the Graduate Program in Neuroscience. This program actively recruits graduate students as do a number of member departments including the Department of Biological Sciences.

Other Neuroscience links at the University of Illinois at Chicago