Journal article
Targeted activation of cholinergic interneurons accounts for the modulation of dopamine by striatal nicotinic receptors
- Abstract:
- Striatal dopamine (DA) is a major player in action selection and reinforcement. DA release is under strong local control by striatal ACh acting at axonal nicotinic ACh receptors (nAChRs) on DA axons. Striatal nAChRs have been shown to control how DA is released in response to ascending activity from DA neurons, and they also directly drive DA release following synchronized activity in a small local cholinergic network. The source of striatal ACh has been thought to arise solely from intrinsic cholinergic interneurons (ChIs), but recent findings have identified a source of cholinergic inputs to striatum from brainstem nuclei, the pedunculopontine nucleus (PPN) and laterodorsal tegmentum (LDT). Here, we used targeted optogenetic activation alongside DA detection with fast-scan cyclic voltammetry to test whether ChIs alone and/or brainstem afferents to the striatum can account for how ACh drives and modulates DA release in rat striatum. We demonstrate that targeted transient light activation of rat striatal ChIs drives striatal DA release, corroborating and extending previous observations in mouse to rat. However, the same light stimulation targeted to cholinergic brainstem afferents did not drive DA release, and nor did it modulate DA release activated subsequently by electrical stimulation, whereas targeted activation of ChIs did so. We were unable to obtain any evidence for DA modulation by PPN/LDT stimulation. By contrast, we could readily identify that striatal ChIs alone are sufficient to provide a source of ACh that powerfully regulates DA via nAChRs.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 891.3KB, Terms of use)
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- Publisher copy:
- 10.1523/ENEURO.0397-17.2018
Authors
- Publisher:
- Society for Neuroscience
- Journal:
- eNeuro More from this journal
- Volume:
- 5
- Issue:
- 5
- Article number:
- e0397
- Publication date:
- 2018-10-12
- Acceptance date:
- 2018-09-16
- DOI:
- EISSN:
-
2373-2822
- Keywords:
- Pubs id:
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pubs:924532
- UUID:
-
uuid:836a3380-7a54-4e5e-9736-83aa86ea47b1
- Local pid:
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pubs:924532
- Source identifiers:
-
924532
- Deposit date:
-
2018-10-08
Terms of use
- Copyright holder:
- Brimblecombe et al
- Copyright date:
- 2018
- Notes:
- © 2018 Brimblecombe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
- Licence:
- CC Attribution (CC BY)
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