Simon Alford


PhD, University of London

The Alford Laboratory

Receptor-mediated Control of Neurotransmitter Release

Fast synaptic transmission in the vertebrate central nervous system is mediated largely via the release of amino acid transmitters. This synaptic transmission is also subject to modulatory influences by myriad receptor subtypes including the amino acid receptors themselves. Such receptors are found on both pre- and post-synaptic elements of the synaptic junction and mediate changes in synaptic efficacy lasting from several milliseconds to several days. In most vertebrates, experimentalist access to the presynaptic terminal to the is limited because of its small size. The lamprey, however, does not possess myelin and as a consequence its axons are large in diameter and may be readily recorded with patch- or micropipettes. Additionally, the tissue of the lamprey central nervous system is optically clear and thin. Being thin it may be kept alive, in vitro but intact, for several days.

My research utilizes these features of this vertebrate preparation to investigate the mechanisms by which synaptic transmission is modulated on both pre- and postsynaptic elements of central nervous system synapses. We are particularly interested in the means by which presynaptic G proteins and presynaptic calcium concentrations modulate the release of neurotransmitter from the presynaptic terminal. Techniques of patch clamp, intracellular recording, and imaging microfluorimetry are utilized to investigate the cellular mechanisms of signal transmission in both the long and short term.

Representative Publications

  • 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. J Neurosci 29: 10221-10233.
  • Kositsky M, Chiappalone M, Alford ST and Mussa-Ivaldi, FA (2009) Brain-machine interactions for assessing the dynamics of neural systems. Front Neurobiotics 3: 1.

  • Yoon E-J, Gerachshenko T, Spiegelberg BD, Alford S and Hamm HE (2007) Gbg regulates exocytosis by interfering with Ca2+-dependent binding of synaptotagmin to the SNARE complex. Mol Pharmacol 72: 1210-1219.
  • Smetana RW, Alford S and Dubuc R (2007) Muscarinic receptor activation elicits sustained, recurring depolarizations in reticulospinal neurons. J Neurophysiol 97: 3181-3192.

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

  • Schwartz E, Gerachshenko T and Alford S (2005) 5-HT prolongs ventral root bursting via presynaptic inhibition of synaptic activity during fictive locomotion in lamprey. J Neurophysiol 93: 980-988.

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

Office: 578 CMET, MC 512