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

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

Yan-Feng Zhang, John N J Reynolds, Stephanie J Cragg

Neuron. 2018 Jun 6;98(5):918-925.e3.

PMID: 29754751

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP122955424	XE-991		122955-42-4	Price

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