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

Abstract:

: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.

journal_name

Neuron

journal_title

Neuron

authors

Tanimura A,Du Y,Kondapalli J,Wokosin DL,Surmeier DJ

doi

10.1016/j.neuron.2018.12.004

subject

Has Abstract

pub_date

2019-02-06 00:00:00

pages

444-458.e6

issue

3

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(18)31080-8

journal_volume

101

pub_type

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