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Local inhibition in a model of the indirect pathway globus pallidus network slows and deregularizes background firing, but sharpens and synchronizes responses to striatal input

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Abstract

The external segment of globus pallidus (GPe) is a network of oscillatory neurons connected by inhibitory synapses. We studied the intrinsic dynamic and the response to a shared brief inhibitory stimulus in a model GPe network. Individual neurons were simulated using a phase resetting model based on measurements from mouse GPe neurons studied in slices. The neurons showed a broad heterogeneity in their firing rates and in the shapes and sizes of their phase resetting curves. Connectivity in the network was set to match experimental measurements. We generated statistically equivalent neuron heterogeneity in a small-world model, in which 99% of connections were made with near neighbors and 1% at random, and in a model with entirely random connectivity. In both networks, the resting activity was slowed and made more irregular by the local inhibition, but it did not show any periodic pattern. Cross-correlations among neuron pairs were limited to directly connected neurons. When stimulated by a shared inhibitory input, the individual neuron responses separated into two groups: one with a short and stereotyped period of inhibition followed by a transient increase in firing probability, and the other responding with a sustained inhibition. Despite differences in firing rate, the responses of the first group of neurons were of fixed duration and were synchronized across cells.

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Acknowledgements

Thanks to Dr. Hitoshi Kita for helpful advice and suggestions throughout the course of this study. Supported by NIH grant NS097185.

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From NIH/NINDS grant NS097185.

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Correspondence to Charles J. Wilson.

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Olivares, E., Higgs, M.H. & Wilson, C.J. Local inhibition in a model of the indirect pathway globus pallidus network slows and deregularizes background firing, but sharpens and synchronizes responses to striatal input. J Comput Neurosci 50, 251–272 (2022). https://doi.org/10.1007/s10827-022-00814-y

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