Catalyzing Inquiry at the Interface of Computing and Biology

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COMPUTATIONAL MODELING AND SIMULATION AS ENABLERS FOR BIOLOGICAL DISCOVERY 185

FIGURE 5.17 Constructing the geometry of a chick ciliary ganglion (CG) somatic spine mat model. A serial EM
tomogram of a CG spine mat was obtained at ~4 nm per voxel resolution. The serial tomogram encompassed a
volume of ~27 mm^3 (~3 μm × 3 μm × 3 μm).
(A) A typical slice through the tomographic volume together with hand-traced contours of the pre- and postsynap-
tic membranes. Tracing and segmentation of presynaptic (cyan) and postsynaptic (red) membrane contours gener-
ated using Xvoxtrace.
(B) Three-dimensional reconstruction of pre- and postsynaptic membrane surfaces as triangle meshes—view look-
ing down onto intracellular face of presynaptic membrane (visualized using DReAMM). The presynaptic mesh is
composed of 100,000 triangles and the postsynaptic mesh is composed of 300,000 triangles.
(C) Postsynaptic membrane surface—view of extracellular face of membrane (presynaptic membrane invisible).
(D) Completed model including postsynaptic membrane subdivided into distinct spines, PSD areas (black regions
with yellow borders), receptor molecules (tiny blue particles on membrane surface), and several neurotransmitter
release sites (red spheres). The membrane was subsequently populated with the desired distributions and densi-
ties of nicotinic acetylcholine receptor (nAChR) types and acetylcholine esterase (AChE) enzyme. Also visible in
(D) are several acetylcholine (ACh) vesicular release sites whose locations are most clearly illustrated in Figure
5.18A.
(E) Magnified view of the state of a simulation of synaptic transmission model as simulated by MCell. State of
system 300 ms after release of 5,000 molecules of acetylcholine (small green ellipsoids) is shown. α7 nAChR types
are shown in blue, and α3* nAChR types are shown in yellow (inactive receptors are semitransparent, and open
receptors are opaque).
SOURCE: Courtesy of Tom Bartol, Salk Institute, San Diego, California.

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