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

• Published in: bioRxiv
• Main Authors: Olivares, Erick, Wilson, Charles J, Goldberg, Joshua A
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 20.02.2024
• Subjects: Basal ganglia; Central nervous system diseases; Connectivity; Firing pattern; Globus pallidus; Movement disorders; Neural networks; Neurodegenerative diseases; Neurons; Parkinson's disease
• DOI: 10.1101/2024.02.19.580929

A 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 considered an indication of the collapse of the normally segregated information channels traversing the BG, and 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 correlations measured from independent neurons in the mouse external GP (GPe) subjected to an identical 1-100 Hz sinusoidal drive. We find that spectral modes of a GPe neurons 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 fires when it is not. We show, mathematically, that the spike cross-intensity function (CIF) is the cross-correlation function of the spike phase distributions of a neuronal pair. Moreover, the distribution of GPe CIF 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 CIF phase delays. Thus, common oscillatory drive gives rise to GPe correlations whose diverse structure and pairwise phase delays reflect their intrinsic properties as captured by their iPRCs.Competing Interest StatementThe authors have declared no competing interest.