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                                             BIOINFORMATICS COLLOQUIUM
						College of Science
                                              George Mason University
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			           Molecular Information Processing in the Brain
						 
                                                   Lukas K. Tamm

              				       University of Virginia

Abstract:
Neurons are connected to one another via synapses. Synapses are
cellular junctions composed of the presynaptic membrane of the sending
cell, a synaptic cleft, and the postsynaptic membrane of the receiving
cell. How are signals transmitted through synapses? How do they jump
two membranes and the synaptic cleft? – In this lecture, I will
explain the molecular interactions that take place in synaptic
transmission, which occurs in a matter of milliseconds!

When an electrical signal arrives at the terminal of the sending
neuron, calcium channels open. The sudden increase in local Ca
concentration in the cell is sensed by a molecule called syaptotagmin,
which decorates the surface of tiny membrane vesicles that are filled
with neurotransmitter (e.g. acetylcholine, serotinin, glycine, GABA).
These so-called synaptic vesicles also display on their surface
another protein, synaptobrevin. Synaptobrevin is like Velcro: it can
stick to another Velcro protein called syntaxin/SNAP25 on the inner
surface of the presynaptic plasma membrane. Together they form
complex, i.e. the SNARE complex, which is a four-helix bundle. When
attaching and activated by Ca-activated synaptotagmin, the SNARE
bundle zippers all the way down to the point where synaptobrevin and
syntaxin are anchored in their respective membranes. This fast
molecular zippering joins the two membranes by membrane fusion. A pore
opens at that fusion site and the neurotransmitter is spilled out into
the synaptic cleft.

The neurotransmitter is then sensed by specific receptors on the
postsynaptic receiving neuron. The structures of these receptors look
like closed irises in the membrane. When the neurotransmitters bind to
the binding sites on these receptors, the irises open and let
potassium and sodium into the cell. This in turn activates other ion
channels along the body of the neuron and generates currents and an
action potential that can propagate along the axon all the way to the
next synapse.

These fascinating molecular pictures of what happens in synaptic
transmission come from a convergence of structural biology (the
science of discovering and rendering macromolecular structures),
electrophysiology (the science of recording tiny electrical currents
from cells), and fast optical imaging techniques often using
high-power multi-color fluorescence microscopy.