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Neurosci."],"accepted":{"date-parts":[[2026,7,12]]},"published-print":{"date-parts":[[2026,8,19]]},"abstract":"<jats:p>The locus ceruleus (LC) provides widespread noradrenergic (NAergic) modulation throughout the brain to influence a wide range of functions, including breathing. Although both anatomical and physiological evidence supports the involvement of the LC in both the upstream integration and the downstream modulation of breathing, the circuitry behind the latter is unknown. Here, we show that LC neurons in adult male and female mice send projections to the K\u00f6lliker\u2013Fuse nucleus (KF), a critical site in the control of breathing. Long duration activation of LC neuron terminals in pontine slices induces persistent inhibitory and excitatory NA currents or increases firing rate in postsynaptic KF neurons. Short stimulation on the other hand leads to VGluT2-dependent rapid release of glutamate that may co-occur with slower NAergic transmission in a monosynaptic circuit. Together these results demonstrate that LC neurons can exert flexible, opposing effects on different timescales via glutamatergic and NAergic signaling onto a key respiratory brainstem nucleus.<\/jats:p>","DOI":"10.1523\/jneurosci.2199-25.2026","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:55:16Z","timestamp":1785261316000},"page":"e2199252026","update-policy":"https:\/\/doi.org\/10.1523\/jneurosci.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Opposing Control of the Respiratory Brainstem on Multiple Timescales Achieved by Noradrenaline and Glutamate Release from the Locus Ceruleus"],"prefix":"10.1523","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-638X","authenticated-orcid":false,"given":"Adrienn G.","family":"Varga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon T.","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian N.","family":"Maletz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Dossat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica S.","family":"Levitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026102706102427000_46.33.e2199252026.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(00)01078-7"},{"key":"2026102706102427000_46.33.e2199252026.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.038"},{"key":"2026102706102427000_46.33.e2199252026.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5196-09.2010"},{"key":"2026102706102427000_46.33.e2199252026.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-090121-014424"},{"key":"2026102706102427000_46.33.e2199252026.5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.28.061604.135709"},{"key":"2026102706102427000_46.33.e2199252026.6","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.81119"},{"key":"2026102706102427000_46.33.e2199252026.7","doi-asserted-by":"crossref","first-page":"100081","DOI":"10.1016\/j.pharmr.2025.100081","article-title":"Neuropeptides as transmitters and regulators of the locus coeruleus noradrenergic system","volume":"77","author":"Becker","year":"2025","journal-title":"Pharmacol Rev"},{"key":"2026102706102427000_46.33.e2199252026.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0582-9"},{"key":"2026102706102427000_46.33.e2199252026.9","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0338-8"},{"key":"2026102706102427000_46.33.e2199252026.10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.biopsycho.2010.01.002","article-title":"Respiratory, autonomic, and experiential responses to repeated inhalations of 20% CO\u2082 enriched air in panic disorder, social phobia, and healthy controls","volume":"84","author":"Blechert","year":"2010","journal-title":"Biol Psychol"},{"key":"2026102706102427000_46.33.e2199252026.11","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00933.2009"},{"key":"2026102706102427000_46.33.e2199252026.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2008.04.002"},{"key":"2026102706102427000_46.33.e2199252026.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-11-06500.1994"},{"key":"2026102706102427000_46.33.e2199252026.14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1164-19.2019"},{"key":"2026102706102427000_46.33.e2199252026.15","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.88673"},{"key":"2026102706102427000_46.33.e2199252026.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.08.057"},{"key":"2026102706102427000_46.33.e2199252026.17","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1993.75.1.5"},{"key":"2026102706102427000_46.33.e2199252026.18","doi-asserted-by":"crossref","unstructured":"De Carvalho D , Patrone LGA , Taxini CL , Biancardi V , Vicente MC , Gargaglioni LH , Kline DD (2014) Neurochemical and electrical modulation of the locus coeruleus: contribution to CO 2 drive to breathe. 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