%Id: README,v 1.0 2002/10/16 21:01 yoyo Exp %



=== About ===

Long-term depression (LTD) in cerebellar Purkinje cells (PCs) is a
candidate mechanism for the molecular and cellular basis of motor
learning and motor coordination (Ito, 1989).

To build a computational model of LTD, we first constructed a kinetic
simulation model using GENESIS/kinetikit (Kuroda et al., 2001). LTD at
parallel fiber (PF)-PCs synapses is induced by a conjunctive
stimulation of PF and climbing fiber (CF) synapses.

Since the main final step in the induction is considered to be the
long-term stable phosphorylation of the AMPA receptor, the final
output of the simulation was set as the phosphorylation state of the
AMPA receptor. We reproduced Kuroda's result in our E-Cell system.

The essential initial step in the LTD induction is the overlapping of
the large elevation in intracellular calcium concentration caused by
CF input-evoked depolarization, and the activation of postsynaptic
glutamate receptors at PF synapses.

However, in our improved simulation using the E-Cell system, we
suceeded in constructing a model of AMPA receptor phosphorylation,
where the AMPA receptor is stimulated by CF synapses only. A large
elevation in calcium concentration caused by influx induces the
activation of neuronal nitric oxide (NO) synthetase, and activated
NO/cGMP pathways give rise to the stable phosphorylation of AMPA
receptors through protein kinase G. Stable activation of this signal
cascade, evoked by the stimulation of only CF synapses, may
phosphorylate AMPA receptors.



=== Files and directories ===

README:     This file
LTD.em:     Model file(em file) for this model
*.cpp:      Process files(cpp files) for this model


=== Running this model ===

1. (If necessary) Convert the .em file to .eml file.

   % ecell3-em2eml LTD.em
   % ls LTD.eml
   LTD.eml


2. Compile .cpp files.

   Run ecell3-dmc for each .cpp file.

   % ecell3-dmc *.cpp

3. Run gecell, File->loadModel and load the LTD.eml file.


