A neurocomputational model of tonic and phasic dopamine in action selection: a comparison with cognitive deficits in Parkinson's disease.
The striatal dopamine signal has multiple facets; tonic level, phasic rise and fall, and variation of the phasic rise/fall depending on the expectation of reward/punishment. We have developed a network model of the striatal direct pathway using an ionic current level model of the medium spiny neuron that incorporates currents sensitive to changes in the tonic level of dopamine. The model neurons in the network learn action selection based on a novel set of mathematical rules that incorporate the phasic change in the dopamine signal. This network model is capable of learning to perform a sequence learning task that in humans is thought to be dependent on the basal ganglia. When both tonic and phasic levels of dopamine are decreased, as would be expected in unmedicated Parkinson's disease (PD), the model reproduces the deficits seen in a human PD group off medication. When the tonic level is increased to normal, but with reduced phasic increases and decreases in response to reward and punishment, respectively, as would be expected in PD medicated with L-Dopa, the model again reproduces the human data. These findings support the view that the cognitive dysfunctions seen in Parkinson's disease are not solely either due to the decreased tonic level of dopamine or to the decreased responsiveness of the phasic dopamine signal to reward and punishment, but to a combination of the two factors that varies dependent on disease stage and medication status.
Guthrie
M
M
Center for Neuroscience, Rutgers University, 197 University Avenue, Suite 209, Newark, NJ 07102, USA. martin.guthrie@u-bordeaux2.fr
Myers
C E
CE
Gluck
M A
MA
D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D003198:Computer Simulation; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008959:Models, Neurological; D016571:Neural Networks, Computer; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D012201:Reward
D000978:Antiparkinson Agents; D007980:Levodopa; D004298:Dopamine