--- - |2+ Key points Medullo‐spinal CSF contacting neurones (CSF‐cNs) located around the central canal are conserved in all vertebrates and suggested to be a novel sensory system intrinsic to the CNS. CSF‐cNs receive GABAergic inhibitory synaptic inputs involving ionotropic GABAA receptors but the contribution of metabotropic GABAB receptors (GABAB‐Rs) was not studied yet. Here, we indicate that CSF‐cNs express functional GABAB‐Rs that inhibit postsynaptic calcium channels but fail to activate inhibitory potassium channel of the kir3‐type. We further show that GABAB‐Rs localize presynaptically on GABAergic and glutamatergic synaptic inputs contacting CSF‐cNs where they inhibit the release of GABA and glutamate. Our data are the first to address the function of GABAB‐Rs in CSF‐cNs 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‐dependent inhibition. Abstract Medullo‐spinal neurones that contact the cerebrospinal fluid (CSF‐cNs) are a population of evolutionary conserved cells located around the central canal. CSF‐cNs activity was shown to be regulated by inhibitory synaptic inputs involving ionotropic GABAA receptors, but the contribution of the G‐protein coupled GABAB receptors was not studied yet. Here, we used a combination of immunofluorescence, electrophysiology and calcium imaging to investigate the expression and function of GABAB‐Rs in CSF‐cNs of the mouse brainstem. We found that CSF‐cNs express GABAB‐Rs, but their selective activation failed to induce G protein‐coupled inwardly‐rectifying potassium (GIRK) currents. Instead, CSF‐cNs express primarily N‐type voltage‐gated calcium (CaV 2.2) channels and GABAB‐Rs recruit Gβγ subunits to inhibit Cav channels activity induced by membrane voltage steps or under physiological conditions by action potentials. Moreover, electrical stimulation evoked in CSF‐cNs GABAergic inhibitory (IPSCs) but also glutamatergic excitatory (EPSCs) synaptic currents, showing that mammalian CSF‐cNs 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‐cNs through a presynaptic mechanism of regulation. In summary, these results are the first to demonstrate the existence of functional postsynaptic GABAB‐Rs in medullar CSF‐cNs as well as presynaptic GABAB auto‐ and heteroreceptors regulating the release of GABA and glutamate. Remarkably, postsynaptic GABAB‐Rs associate with CaV but not GIRK channels indicating that GABAB‐Rs function as a calcium signalling modulator without GIRK‐dependent inhibition in CSF‐cNs. This article is protected by copyright. All rights reserved - 'The Journal of Physiology, Volume 0, Issue ja, -Not available-. '