Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation.

Neuron
Yan-Feng ZhangStephanie J Cragg

Abstract

Cholinergic interneurons (ChIs) of the striatum pause their firing in response to salient stimuli and conditioned stimuli after learning. Several different mechanisms for pause generation have been proposed, but a unifying basis has not previously emerged. Here, using in vivo and ex vivo recordings in rat and mouse brain and a computational model, we show that ChI pauses are driven by withdrawal of excitatory inputs to striatum and result from a delayed rectifier potassium current (IKr) in concert with local neuromodulation. The IKr is sensitive to Kv7.2/7.3 blocker XE-991 and enables ChIs to report changes in input, to pause on excitatory input recession, and to scale pauses with input strength, in keeping with pause acquisition during learning. We also show that although dopamine can hyperpolarize ChIs directly, its augmentation of pauses is best explained by strengthening excitatory inputs. These findings provide a basis to understand pause generation in striatal ChIs. VIDEO ABSTRACT.

Citations

Apr 18, 2020·The European Journal of Neuroscience·Cecilia Tubert, Mario Gustavo Murer
Jan 11, 2020·Frontiers in Pharmacology·Nicolas MalletCorinne Beurrier
Mar 7, 2020·Acta Pharmacologica Sinica·Changliang Liu
Sep 26, 2019·Frontiers in Molecular Neuroscience·Noorya Yasmin AhmedNathalie Dehorter
May 29, 2021·Neuroscience·Rodrigo Manuel Paz, Mario Gustavo Murer

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Methods Mentioned

BETA
dissection

Software Mentioned

MathWorks
pCLAMP
SPIKE2
MATLAB
NEURON
Spike2 CED
Clampfit
Clampex

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