{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:32:21Z","timestamp":1790753541033,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,12,10]],"date-time":"2018-12-10T00:00:00Z","timestamp":1544400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007586","name":"Aix-Marseille Universit\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Medullo\u2010spinal CSF contacting neurones (CSF\u2010cNs) located around the central canal are conserved in all vertebrates and suggested to be a novel sensory system intrinsic to the CNS.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CSF\u2010cNs receive GABAergic inhibitory synaptic inputs involving ionotropic GABA<jats:sub>A<\/jats:sub> receptors, but the contribution of metabotropic GABA<jats:sub>B<\/jats:sub> receptors (GABA<jats:sub>B<\/jats:sub>\u2010Rs) has not yet been studied.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here, we indicate that CSF\u2010cNs express functional GABA<jats:sub>B<\/jats:sub>\u2010Rs that inhibit postsynaptic calcium channels but fail to activate inhibitory potassium channel of the Kir3\u2010type.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We further show that GABA<jats:sub>B<\/jats:sub>\u2010Rs localise presynaptically on GABAergic and glutamatergic synaptic inputs contacting CSF\u2010cNs, where they inhibit the release of GABA and glutamate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data are the first to address the function of GABA<jats:sub>B<\/jats:sub>\u2010Rs in CSF\u2010cNs and show that on the presynaptic side they exert a classical synaptic modulation whereas at the postsynaptic level they have an atypical action by modulating calcium signalling without inducing potassium\u2010dependent inhibition.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Medullo\u2010spinal neurones that contact the cerebrospinal fluid (CSF\u2010cNs) are a population of evolutionary conserved cells located around the central canal. CSF\u2010cN activity has been shown to be regulated by inhibitory synaptic inputs involving ionotropic GABA<jats:sub>A<\/jats:sub> receptors, but the contribution of the G\u2010protein coupled GABA<jats:sub>B<\/jats:sub> receptors has not yet been studied. Here, we used a combination of immunofluorescence, electrophysiology and calcium imaging to investigate the expression and function of GABA<jats:sub>B<\/jats:sub>\u2010Rs in CSF\u2010cNs of the mouse brainstem. We found that CSF\u2010cNs express GABA<jats:sub>B<\/jats:sub>\u2010Rs, but their selective activation failed to induce G protein\u2010coupled inwardly rectifying potassium (GIRK) currents. Instead, CSF\u2010cNs express primarily N\u2010type voltage\u2010gated calcium (Ca<jats:sub>V<\/jats:sub>2.2) channels, and GABA<jats:sub>B<\/jats:sub>\u2010Rs recruit G\u03b2\u03b3 subunits to inhibit Ca<jats:sub>V<\/jats:sub> channel activity induced by membrane voltage steps or under physiological conditions by action potentials. Moreover, using electrical stimulation, we indicate that GABAergic inhibitory (IPSCs) and excitatory glutamatergic (EPSCs) synaptic currents can be evoked in CSF\u2010cNs showing that mammalian CSF\u2010cNs are also under excitatory control by glutamatergic synaptic inputs. We further demonstrate that baclofen reversibly reduced the amplitudes of both IPSCs and EPSCs evoked in CSF\u2010cNs through a presynaptic mechanism of regulation. In summary, these results are the first to demonstrate the existence of functional postsynaptic GABA<jats:sub>B<\/jats:sub>\u2010Rs in medullar CSF\u2010cNs, as well as presynaptic GABA<jats:sub>B<\/jats:sub> auto\u2010 and heteroreceptors regulating the release of GABA and glutamate. Remarkably, postsynaptic GABA<jats:sub>B<\/jats:sub>\u2010Rs associate with Ca<jats:sub>V<\/jats:sub> but not GIRK channels, indicating that GABA<jats:sub>B<\/jats:sub>\u2010Rs function as a calcium signalling modulator without GIRK\u2010dependent inhibition in CSF\u2010cNs.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277172","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T16:14:55Z","timestamp":1542039295000},"page":"631-651","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["GABA<sub>B<\/sub> receptors modulate Ca<sup>2+<\/sup> but not G protein\u2010gated inwardly rectifying K<sup>+<\/sup> channels in cerebrospinal\u2010fluid contacting neurones of mouse brainstem"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5076-9753","authenticated-orcid":false,"given":"Nina","family":"Jur\u010di\u0107","sequence":"first","affiliation":[{"name":"Aix 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