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dc.contributor.authorChung, Leeyup
dc.contributor.authorJing, Miao
dc.contributor.authorLi, Yulong
dc.contributor.authorTapper, Andrew R
dc.date.accessioned2023-10-30T14:00:54Z
dc.date.available2023-10-30T14:00:54Z
dc.date.issued2023-08-10
dc.identifier.citationChung L, Jing M, Li Y, Tapper AR. Feed-forward Activation of Habenula Cholinergic Neurons by Local Acetylcholine. Neuroscience. 2023 Oct 1;529:172-182. doi: 10.1016/j.neuroscience.2023.07.030. Epub 2023 Aug 10. PMID: 37572877.en_US
dc.identifier.eissn1873-7544
dc.identifier.doi10.1016/j.neuroscience.2023.07.030en_US
dc.identifier.pmid37572877
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52662
dc.description.abstractWhile the functional and behavioral role of the medial habenula (MHb) is still emerging, recent data indicate an involvement of this nuclei in regulating mood, aversion, and addiction. Unique to the MHb is a large cluster of cholinergic neurons that project to the interpeduncular nucleus and densely express acetylcholine receptors (AChRs) suggesting that the activity of these cholinergic neurons may be regulated by ACh itself. Whether endogenous ACh from within the habenula regulates cholinergic neuron activity has not been demonstrated. Supporting a role for ACh in modulating MHb activity, acetylcholinesterase inhibitors increased the firing rate of MHb cholinergic neurons in mouse habenula slices, an effect blocked by AChR antagonists and mediated by ACh which was detected via expressing fluorescent ACh sensors in MHb in vivo. To test if cholinergic afferents innervate MHb cholinergic neurons, we used anterograde and retrograde viral tracing to identify cholinergic inputs. Surprisingly, tracing experiments failed to detect cholinergic inputs into the MHb, including from the septum, suggesting that MHb cholinergic neurons may release ACh within the MHb to drive cholinergic activity. To test this hypothesis, we expressed channelrhodopsin in a portion of MHb cholinergic neurons while recording from non-opsin-expressing neurons. Light pulses progressively increased activity of MHb cholinergic neurons indicating feed-forward activation driven by MHb ACh release. These data indicate MHb cholinergic neurons may utilize a unique feed-forward mechanism to synchronize and increase activity by releasing local ACh.en_US
dc.language.isoenen_US
dc.relation.ispartofNeuroscienceen_US
dc.relation.urlhttps://doi.org/10.1016/j.neuroscience.2023.07.030en_US
dc.rightsCopyright 2023 The Author(s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectacetylcholineen_US
dc.subjectfeed forward activationen_US
dc.subjectmedial habenulaen_US
dc.subjectseptumen_US
dc.titleFeed-forward Activation of Habenula Cholinergic Neurons by Local Acetylcholineen_US
dc.typeJournal Articleen_US
dc.source.journaltitleNeuroscience
dc.source.volume529
dc.source.beginpage172
dc.source.endpage182
dc.source.countryUnited States
dc.identifier.journalNeuroscience
refterms.dateFOA2023-10-30T14:00:55Z
dc.contributor.departmentBrudnick Neuropsychiatric Research Instituteen_US
dc.contributor.departmentNeurobiologyen_US
dc.contributor.departmentTapper Lab


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Copyright 2023 The Author(s). Published by Elsevier Ltd on behalf of IBRO.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2023 The Author(s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).