Readme for model associated with the paper
Prescott SA, De Koninck Y. (2005) Integration time in a subset of
spinal lamina I neurons is lengthened by sodium and calcium currents
acting synergistically to prolong subthreshold depolarization.
J Neurosci. 25(19):4743-54.
Lamina I of the spinal dorsal horn plays an important role in
processing and relaying nociceptive information to the brain.
It comprises physiologically distinct cell types that process
information in fundamentally different ways: tonic neurons fire
repetitively during stimulation and display prolonged EPSPs,
suggesting operation as integrators, whereas single-spike neurons
act like coincidence detectors. Using whole-cell recordings from a
rat spinal slice preparation,weset out to determine the basis for
prolonged EPSPs in tonic cells and the implications for signal
processing. Kinetics of synaptic currents could not explain
differences in EPSP kinetics. Instead, tonic neurons were found to
express a persistent sodium current, INa,P , that amplified and
prolonged depolarization in response to brief stimulation. Tonic
neurons also expressed a persistent calcium current, ICa,P , that
contributed to prolongation but not to amplification. Simulations
using NEURON software demonstrated that INa,P was necessary and
sufficient to explain amplification, whereas INa,P and ICa,P acted
synergistically to prolong depolarization: initial activation of the
slower current (ICa,P) depended on the faster current (INa,P) but
maintained activation of the faster current likewise depended on the
slower current. Additional investigation revealed that INa,P and
ICa,P could dramatically increase integration time (>30X) and
thereby encourage temporal summation but at the expense of spike
time precision. Thus, by prolonging subthreshold depolarization,
intrinsic inward currents allow tonic neurons in spinal lamina I
to specialize as integrators that are optimally suited to encode
Model demonstrates mechanism whereby two kinetically distinct
inward currents act synergistically to prolong subthreshold
depolarization. The important currents are a persistent Na current
(with fast kinetics) and a persistent Ca current (with slower
kinetics). Model also includes a slow K current and transient Ca
current, in addition to standard HH currents. Model parameters are
set to values used in Fig. 8A. Simulation shows prolonged
depolarizations in response to two brief stimuli.
Auto-launch from ModelDB (unix and pc). Press init and run()
Alternatively download the zip archive. Then depending on your platform:
Expand the archive. Run mknrndll and traverse to the newly created
directory and click make the nrnmech.dll
Then double click the mosinit.hoc file in windows explorer.
Expand the archive with
Compile the NEURON mod files by running nrnivmodl in the newly created directory.
to start the simulation
mac OS X.
Drag and drop the zip file on the mos2nrn icon in the Neuron application folder.
The mod files are automatically compiled and the simulation starts automatically.
Note: The voltage-gated mechanisms have been revised to allow
adaptive integration, rather than fixed time step integration
with dt = 0.01 ms as was done in the paper. This allows the
simulation to run faster without loss of accuracy. Also, the
initial membrane potential has been changed from -63 to -62.65 mV,
which is the resting potential for this particular model