title: Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model.
abstract: The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion-induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN-MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion-induced changes to CTX-MSN D1, CTX-MSN D2, TA-MSN, and MSN-MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function.
authors.affiliation: Science for Life Laboratory, School of Computer Science and Communication, KTH Royal Institute of Technology, Box 1031, 17121 Solna, Sweden; Stockholm Brain Institute, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Lindahl
authors.affiliation: Science for Life Laboratory, School of Computer Science and Communication, KTH Royal Institute of Technology, Box 1031, 17121 Solna, Sweden; Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden; Stockholm Brain Institute, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Jeanette
authors.identifier: 0000-0002-0550-0739
authors.initials: J
authors.lastname: Hellgren Kotaleski
mesh_terms: D000200:Action Potentials; D000818:Animals; D001479:Basal Ganglia / Q000502:physiology* / Q000503:physiopathology; D003198:Computer Simulation; D004298:Dopamine / Q000378:metabolism*; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000503:physiopathology; D051381:Rats; D020531:Subthalamic Nucleus / Q000502:physiology / Q000503:physiopathology
chemical_list: D016627:Oxidopamine; D004298:Dopamine
keywords: Parkinson’s disease; basal ganglia; dopamine; inhibition; network dynamics; spiking network model