The brain is the source of thoughts, perceptions, emotions, memories and actions. Neural signaling, the foundation of brain activity, must be precisely regulated to prevent neuronal disorders that may cause Parkinson's disease, schizophrenia, compulsive behaviors and addiction. Such a precise regulation is achieved by key signaling proteins, voltage-gated sodium and potassium channels for electrical signaling and calcium - bound synaptotagmin for chemical signaling. Here, innovations in computer simulation techniques will be used to investigate the molecular mechanism of neural firing induced by voltage-gated sodium and potassium channels and membrane fusion triggered by synaptotagmin.
Neurons in the brain form a closely knit communication network with other
neurons. Each neuron sends messages through up to thousands of cell-cell communication
channels, so-called synapses. To avoid communication chaos, the messages of each neuron
are chemically encoded as if neurons speak English to some neurons and French
to others. The neurons employ an extremely efficient
encoding system, packaging chemical message molecules, so-called neurotransmitters,
in spherical vesicles encapsulated by a lipid membrane just like the whole neuron is
encapsulated by a membrane. The vesicles aggregate near the presynaptic site of the membrane,
ready to release their neurotransmitters into the space between neurons at the synapse,
the so-called synaptic cleft. When a sender neuron becomes electrically active, as it
wants to "speak",
the electrical activity releases
Calcium ions at the pre-synaptic cell that trigger merging
(fusion) of vesicles with
the sender neuron's membrane.
At this point the neurotransmitter molecules flow into the synaptic cleft.
The receiver neuron "hears" the signal by receiving the neurotransmitter
molecules on receptors in the postsynaptic membrane, inducing as a result an electrical
signal in the receiver neuron.
involves a group of proteins that make vesicles ready for the release and
proteins that execute the Calcium-triggered step, among the latter
synaptotagmin I. As reported recently, researchers have proposed
with the help of computer simulations using NAMD how
synaptotagmin I acts.
The simulations suggest that the experimentally observed structure of synaptotagmin
I measured in vitro in a crystal/NMR form of the protein differs from the
active, in situ form of synaptotagmin I.
The finding, if true, will be a dramatic example for the role of computing in biology
where the computer often complements observation studying, as in the present case,
biomolecules in situ, namely their natural environment, rather than in vitro,
namely in an artificial environment.
Please read more on our neuron transmission website.
Biological visuo-motor control of a pneumatic robot arm.
Michael Zeller, K. R. Wallace, and Klaus Schulten. In Dagli et al., editors, Intelligent Engineering Systems Through Artificial Neural Networks, volume 5, pp. 645-650, New York, 1995. American Society of Mechanical Engineers.
A "neural gas" network learns topologies.
Thomas Martinetz and Klaus Schulten. In Teuvo Kohonen, Kai Mäkisara, Olli Simula, and Jari Kangas, editors, Artificial Neural Networks, pp. 397-402. Elsevier, Amsterdam, 1991.