Phase delays between mouse globus pallidus neurons entrained by common oscillatory drive arise from their intrinsic properties, not their coupling

Author:

Olivares Erick,Wilson Charles J.,Goldberg Joshua A.ORCID

Abstract

AbstractA hallmark of Parkinson’s disease is the appearance of correlated oscillatory discharge throughout the cortico-basal ganglia (BG) circuits. In the primate globus pallidus (GP), where the discharge of GP neurons is normally uncorrelated, pairs of GP neurons exhibit oscillatory spike correlations with a broad distribution of pairwise phase delays in experimental parkinsonism. The transition to oscillatory correlations is thought to indicate the collapse of the normally segregated information channels traversing the BG. The large phase delays are thought to reflect pathological changes in synaptic connectivity in the BG. Here we study the structure and phase delays of spike correlations measured from neurons in the mouse external GP (GPe) subjected to identical 1-100 Hz sinusoidal drive but recorded in separate experiments. First, we find that spectral modes of a GPe neuron’s empirical instantaneous phase response curve (iPRC), elucidate at what phases of the oscillatory drive the GPe neuron locks when it is entrained, and the distribution of phases at which it spikes when it is not. Then, we show that in this case the pairwise spike cross-correlation equals the cross-correlation function of these spike phase distributions. Finally, we show that the distribution of GPe phase delays arises from the diversity of iPRCs, and is broadened when the neurons become entrained. Modeling GPe networks with realistic intranuclear connectivity demonstrates that the connectivity decorrelates GPe neurons without affecting phase delays. Thus, common oscillatory input gives rise to GPe correlations whose structure and pairwise phase delays reflect their intrinsic properties captured by their iPRCs.Significance StatementThe external globus pallidus (GPe) is a hub in the basal ganglia, whose neurons impose a barrage of inhibitory synaptic currents on neurons of the subthalamic nucleus, substantia nigra and internal globus pallidus. GPe neurons normally fire independently, but in experimental parkinsonism, they become correlated in the frequency range associated with the pathological rhythms seen in human Parkinson’s disease, raising the possibility that they may be generators of the pathological oscillation. We drove individual pallidal neurons with an oscillatory input over a wide range of frequencies. Cross-correlations of these neurons reproduced many of the features seen in parkinsonism, suggesting that their correlated oscillations might derive from a shared input rather than internal interconnections.

Publisher

Cold Spring Harbor Laboratory

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