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Neuron. 2018 Jun 6;98(5):918-925.e3. doi: 10.1016/j.neuron.2018.04.027. Epub 2018 May 10.

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

Author information

1
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK; Oxford Parkinson's Disease Centre, Oxford OX1 3PT, UK; Department of Anatomy and the Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin 9054, NZ.
2
Department of Anatomy and the Brain Health Research Centre, Brain Research New Zealand, University of Otago, Dunedin 9054, NZ.
3
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK; Oxford Parkinson's Disease Centre, Oxford OX1 3PT, UK. Electronic address: stephanie.cragg@dpag.ox.ac.uk.

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.

KEYWORDS:

basal ganglia; cholinergic interneuron; corticostriatal; delayed rectification; dopamine; excitatory input; nigrostriatal; pause response; striatum; thalamostriatal

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