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A spiking computational model for striatal cholinergic interneurons

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Abstract

Cholinergic interneurons in the striatum, also known as tonically active interneurons or TANs, are thought to have a strong effect on corticostriatal plasticity and on striatal activity and outputs, which in turn play a critical role in modulating downstream basal ganglia activity and movement. Striatal TANs can exhibit a variety of firing patterns and responses to synaptic inputs; furthermore, they have been found to display various surges and pauses in activity associated with sensory cues and reward delivery in learning as well as with motor tic production. To help explain the factors that contribute to TAN activity patterns and to provide a resource for future studies, we present a novel conductance-based computational model of a striatal TAN. We show that this model produces the various characteristic firing patterns observed in recordings of TANs. With a single baseline tuning associated with tonic firing, the model also captures a wide range of TAN behaviors found in previous experiments involving a variety of manipulations. In addition to demonstrating these results, we explain how various ionic currents in the model contribute to them. Finally, we use this model to explore the contributions of the acetylcholine released by TANs to the production of surges and pauses in TAN activity in response to strong excitatory inputs. These results provide predictions for future experimental testing that may help with efforts to advance our understanding of the role of TANs in reinforcement learning and in motor disorders such as Tourette’s syndrome.

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Funding

This work was partially supported by the NSF CRCNS under Award DMS 1724240 and the NSF under Award DMS 1951095. The authors thank Izhar Bar-Gad and Fred Hamker and their lab members for discussions related to this work.

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Authors and Affiliations

  1. Department of Mathematics, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Marcello G. Codianni & Jonathan E. Rubin

  2. Center for the Neural Basis of Cognition, Pittsburgh, PA, 15260, USA

    Jonathan E. Rubin

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  1. Marcello G. Codianni
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  2. Jonathan E. Rubin
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Correspondence to Jonathan E. Rubin.

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Data availability

No original experimental data were involved in this study. Codes used for model simulations will be made publicly available at ModelDB (https://senselab.med.yale.edu/ModelDB/) upon acceptance of this work for publication.

Conflict of interest

The authors declare no competing financial interests.

Significance statement

Despite a growing recognition that striatal cholinergic interneurons, also known as tonically active neurons (TANs), can significantly impact synaptic plasticity and firing patterns of projection neurons in the striatum, there has been relatively little computational work to simulate and analyze their properties. We address this gap by developing a computational model of TANs, fit to match a large collection of experimental results. Simulations of the computational model allow us to analyze the roles of various transmembrane currents in producing TAN responses and the contribution of acetylcholine released by TANs in sculpting their activity in response to excitatory inputs, which could have implications for reinforcement learning and for motor tics in conditions such as Tourette’s syndrome.

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Codianni, M.G., Rubin, J.E. A spiking computational model for striatal cholinergic interneurons. Brain Struct Funct 228, 589–611 (2023). https://doi.org/10.1007/s00429-022-02604-9

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