Elghaba, R., Vautrelle, N. and Bracci, E. (2016) Mutual Control of Cholinergic and Low-Threshold Spike Interneurons in the Striatum. Frontiers in Cellular Neuroscience, 10. 111. ISSN 1662-5102
Abstract
The striatum is the largest nucleus of the basal ganglia and is crucially involved in action selection and reward processing. Cortical and thalamic inputs to the striatum are processed by local networks in which several classes of interneurons play an important, but still poorly understood role. Here we investigated the interactions between cholinergic and low-threshold spike (LTS) interneurons. LTS interneurons were hyperpolarized by co-application of muscarinic and nicotinic receptor antagonists (atropine and mecamylamine, respectively). Mecamylamine alone also caused hyperpolarizations, while atropine alone caused depolarizations and increased firing. LTS interneurons were also under control of tonic GABA, as application of the GABAA receptor antagonist picrotoxin caused depolarizations and increased firing. Frequency of spontaneous GABAergic events in LTS interneurons was increased by co-application of atropine and mecamylamine or by atropine alone, but reduced by mecamylamine alone. In the presence of picrotoxin and tetrodotoxin (TTX), atropine and mecamylamine depolarized the LTS interneurons. We concluded that part of the excitatory effects of tonic acetylcholine (ACh) on LTS interneurons were due to cholinergic modulation of tonic GABA. We then studied the influence of LTS interneurons on cholinergic interneurons. Application of antagonists of somatostatin or neuropeptide Y (NPY) receptors or of an inhibitor of nitric oxide synthase (L-NAME) did not cause detectable effects in cholinergic interneurons. However, prolonged synchronized depolarizations of LTS interneurons (elicited with optogenetics tools) caused slow-onset depolarizations in cholinergic interneurons, which were often accompanied by strong action potential firing and were fully abolished by L-NAME. Thus, a mutual excitatory influence exists between LTS and cholinergic interneurons in the striatum, providing an opportunity for sustained activation of the two cell types. This activation may endow the striatal microcircuits with the ability to enter a high ACh/high nitric oxide regime when adequately triggered by external excitatory stimuli to these interneurons.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2016 Elghaba, Vautrelle and Bracci. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | GABA; acetylcholine; interneuron; mutual excitation; nitric oxide; striatum |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL MR/K022512/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Jun 2016 09:57 |
Last Modified: | 23 Jun 2023 22:05 |
Published Version: | http://dx.doi.org/10.3389/fncel.2016.00111 |
Status: | Published |
Publisher: | Frontiers |
Refereed: | Yes |
Identification Number: | 10.3389/fncel.2016.00111 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:99561 |