TY - JOUR T1 - Untangling basal ganglia network dynamics and function – role of dopamine depletion and inhibition investigated in a spiking network model JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0156-16.2016 SP - ENEURO.0156-16.2016 AU - Mikael Lindahl AU - Jeanette Hellgren Kotaleski Y1 - 2016/12/22 UR - http://www.eneuro.org/content/early/2016/12/22/ENEURO.0156-16.2016.abstract N2 - The basal ganglia are a crucial brain system for behavioral selection and the 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. Recording of the neuronal activity in the subthalamic nucleus (STN) and Type A (TA; arkypallidal) and type I (TI; prototypical) neurons in globus pallidus externa (GPe) are 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 cortico-striatal 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/or the 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 which could both improve action selection ability and at the same time reduce the oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding on the relation between network dynamics and network function.Significance Statement Basal ganglia (BG) are important for selection of behavior, and in Parkinsons’s disease (PD) dopamine deficiency causes BG to malfunction. Also the network dynamical behaviour changes, and oscillations and spike synchronization develop. We build a BG network model and use it to better understand how network parameters contribute to function as well as network dynamics, and how functionality can be recovered in the disease state. Our findings improve the general understanding of how BG function, which network parameters are associated with an impaired function vs when disease-associated parameter changes can be seen as compensatory. Our results may contribute to novel approaches for the treatment of PD. ER -