Opposing Control of the Respiratory Brainstem on Multiple Timescales Achieved by Noradrenaline and Glutamate Release from the Locus Ceruleus.

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 Kölliker-Fuse 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.