We extended Izhikevich's reduced model of the striatal medium spiny neuron (MSN) to account for dopaminergic modulation of its intrinsic ion channels and synaptic inputs. We tuned our D1 and D2 receptor MSN models using data from a recent (Moyer et al, 2007) large-scale compartmental model. Our new models capture the input-output relationships for both current injection and spiking input with remarkable accuracy, despite the order of magnitude decrease in system size. They also capture the paired pulse facilitation shown by MSNs. Our dopamine models predict that synaptic effects dominate intrinsic effects for all levels of D1 and D2 receptor activation. Our analytical work on these models predicts that the MSN is never bistable. Nonetheless, these MSN models can produce a spontaneously bimodal membrane potential similar to that recently observed in vitro following application of NMDA agonists. We demonstrate that this bimodality is created by modelling the agonist effects as slow, irregular and massive jumps in NMDA conductance and, rather than a form of bistability, is due to the voltage-dependent blockade of NMDA receptors
Model Type: Neuron or other electrically excitable cell
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell
Receptors: D1; D2; GabaA; AMPA; NMDA
Transmitters: Dopamine
Model Concept(s): Action Potential Initiation; Parameter Fitting; Simplified Models; Parkinson's; Bifurcation
Simulation Environment: MATLAB
Implementer(s): Humphries, Mark D [m.d.humphries at shef.ac.uk]
References:
Humphries MD, Lepora N, Wood R, Gurney K. (2009). Capturing dopaminergic modulation and bimodal membrane behaviour of striatal medium spiny neurons in accurate, reduced models. Frontiers in computational neuroscience. 3 [PubMed]