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Cholinergic Interneurons Amplify Thalamostriatal Excitation of Striatal Indirect Pathway Neurons in Parkinson's Disease Models.

Asami Tanimura | Yijuan Du | Jyothisri Kondapalli | David L Wokosin | D James Surmeier
Neuron | 2019

The motor symptoms of Parkinson's disease (PD) are thought to stem from an imbalance in the activity of striatal direct- and indirect-pathway spiny projection neurons (SPNs). Disease-induced alterations in the activity of networks controlling SPNs could contribute to this imbalance. One of these networks is anchored by the parafascicular nucleus (PFn) of the thalamus. To determine the role of the PFn in striatal PD pathophysiology, optogenetic, chemogenetic, and electrophysiological tools were used in ex vivo slices from transgenic mice with region-specific Cre recombinase expression. These studies revealed that in parkinsonian mice, the functional connectivity of PFn neurons with indirect pathway SPNs (iSPNs) was selectively enhanced by cholinergic interneurons acting through presynaptic nicotinic acetylcholine receptors (nAChRs) on PFn terminals. Attenuating this network adaptation by chemogenetic or genetic strategies alleviated motor-learning deficits in parkinsonian mice, pointing to a potential new therapeutic strategy for PD patients.

Pubmed ID: 30658860

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This is a list of tools and resources that we have found mentioned in this publication.


NeuralEnsemble (tool)

RRID:SCR_001382

Community-based initiative to promote and co-ordinate open-source software development in neuroscience hosting a number of software projects for computational and systems neuroscience, including PyNN, NeuroTools, Brian, Neo, OpenElectrophy, libNeuroML and Sumatra. Some of the projects use their Trac installation, others are on GitHub. By grouping these projects together under the NeuralEnsemble umbrella, the aim is to maximize interoperability and build components that can easily be combined into powerful systems for brain simulations and advanced data analysis. An annual CodeJam workshop is organized, bringing together scientists, graduate students, and scientific programmers to share ideas, present their work, and write code together. These workshops have been hugely effective in catalyzing open-source neuroscience software development. There is a NeuralEnsemble Google group for discussion of collaborative neuroscience software development (mainly in Python, but users of other languages are welcome!) and to provide software support.

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RRID:SCR_011323

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RRID:SCR_003070

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RRID:IMSR_JAX:016204

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RRID:SCR_001622

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RRID:SCR_014198

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RRID:IMSR_JAX:000664

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RRID:IMSR_JAX:030255

Mus musculus with name B6;FVB-Tg(Drd2-EGFP/Rpl10a)CP101Htz/J from IMSR.

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Limelight (software resource)

RRID:SCR_014254

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Neo (software resource)

RRID:SCR_000634

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RRID:MMRRC_031125-UCD

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RRID:SCR_007370

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RRID:SCR_000325

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B6;129S6-Chattm2(cre)Lowl/J (organism)

RRID:IMSR_JAX:006410

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