Uncoupling the roles of firing rates and spike bursts in shaping the STN-GPe beta band oscillations

Abstract

12The excess of 15-30 Hz (β-band) oscillations in the basal ganglia is one of the key 13 signatures of Parkinson's disease (PD). The STN-GPe network is integral to generation 14 and modulation of β band oscillations in basal ganglia. However, the role of changes in 15 the firing rates and spike bursting of STN and GPe neurons in shaping these oscillations 16 has remained unclear. In order to uncouple their effects, we studied the dynamics of 17 STN-GPe network using numerical simulations. In particular, we used a neuron model, 18 in which firing rates and spike bursting can be independently controlled. Using this 19 model, we found that while STN firing rate is predictive of oscillations but GPe firing 20 rate is not. The effect of spike bursting in STN and GPe neurons was state-dependent . 21 That is, only when the network was operating in a state close to the border of 22 oscillatory and non-oscillatory regimes, spike bursting had a qualitative effect on the β 23 band oscillations. In these network states, an increase in GPe bursting enhanced the 24 oscillations whereas an equivalent proportion of spike bursting in STN suppressed the 25 oscillations. These results provide new insights into the mechanisms underlying the 26 transient β bursts and how duration and power of β band oscillations may be controlled 27 by an interplay of GPe and STN firing rates and spike bursts. 28Author summary 29The STN-GPe network undergoes a change in firing rates as well as increased bursting 30 during excessive β band oscillations during Parkinson's disease. In this work we 31 uncouple their effects by using a novel neuron model and show that presence of 32 oscillations is contingent on the increase in STN firing rates, however the effect of spike 33 bursting on oscillations depends on the network state. In a network state on the border 34 of oscillatory and non-oscillatory regime, GPe spike bursting strengthens oscillations. 35The effect of spike bursting in the STN depends on the proportion of GPe neurons 36 bursting. These results suggest a mechanism underlying a transient β band oscillation 37 bursts often seen in experimental data. 38 Introduction 39Parkinson's disease (PD) is a progressive neurodegenerative brain disease caused by the 40 depletion of dopamine neurons in the substantia nigra pars compacta (SNc) [1]. Loss of 41 March 4, 2020 1/36 dopamine causes a host of cognitive and motor impairments. The dopaminergic cells 42 death can be attributed many causes e.g. genetic mutations [1], pathogen that affects 43 the gut microbome and travels to the central nervous systems [2, 3], excitotoxicity [4], 44 and mitichondrial dysfunction [5] etc. [6]. While the etiology of PD is still debated, the 45 behavioral symptoms of PD are accompanied by various changes in the neuronal 46 activity in Basal Ganglia (BG): e.g, increased firing rate of D2 type dopamine receptors 47 expressing striatal neurons [7-9]; increase in spike bursts in striatum, globus pallidus 48 externa (GPe), globus pallidus interna (GPi) and subthalamic nucle...