A spiking computational model for striatal cholinergic interneurons.

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.