Komendantov AO, Komendantova OG, Johnson SW, Canavier CC (2004) A modeling study suggests complementary roles for GABAA and NMDA receptors and the SK channel in regulating the firing pattern in midbrain dopamine neurons. J Neurophysiol 91:346-57
Midbrain dopaminergic (DA) neurons in vivo exhibit two major firing patterns: single-spike firing and burst firing. The firing pattern expressed is dependent on both the intrinsic properties of the neurons and their excitatory and inhibitory synaptic inputs. Experimental data suggest that the activation of N-methyl-D-aspartate (NMDA) and GABAA receptors is a crucial contributor to the initiation and suppression of burst firing, respectively, and that blocking Ca(2+)-activated potassium SK channels can facilitate burst firing.
A multi-compartmental model of a DA neuron with a branching structure was developed and calibrated based on in vitro experimental data to explore the effects of different levels of activation of NMDA and GABAA receptors as well as the modulation of the SK current on the firing activity. The simulated tonic activation of GABAA receptors was calibrated by taking into account the difference in the electrotonic properties in vivo versus in vitro.
Although NMDA-evoked currents are required for burst generation in the model, currents evoked by GABAA-receptor activation can also regulate the firing pattern. For example, the model predicts that increasing the level of NMDA receptor activation can produce excessive depolarization that prevents burst firing, but a concurrent increase in the activation of GABAA receptors can restore burst firing. Another prediction of the model is that blocking the SK channel current in vivo will facilitate bursting, but not as robustly as blocking the GABAA receptors.
These model files were supplied by Anna Kuznetsova.
Auto-launch from ModelDB for a graphical interface to the model.
If you have installed NEURON with mpi on x86_64 systems you can double check that /usr/local/neuron/x86_64/bin is in your path.
To compile the code (under unix) type:
nrnivmodl
In order to run the code:
- If you want a graphical user interface, set
back = 0indamodel.hoc, then type:
x86_64/special damodel.hoc -
and hit the init and run button.
- To run simulations in the background set
back = 1and run:
mpirun -nolocal x86_64/special damodel.hoc >& myfile.dat &
(This prints soma and dendrite voltages and some currents to myfile.dat)
Run in the background generates state.new file. To restart from these last data, copy state.new over state.old and set restart = 1 in damodel.hoc. (This works both for GUI and background).
2025-05-27 – Standardized to Markdown.