Semilunar nucleus neurons are highly excitable and potentiated by group I mGluRs to drive descending excitation to the mouse MNTB

Medial nucleus of the trapezoid body (MNTB) neurons receive one of the largest synapses in the mammalian brain, the calyx of Held; however, multiple studies reported additional non-calyceal excitatory inputs of largely unresolved origin to MNTB neurons. Most recently, the semilunar nucleus (SLN) was identified as a potential source of such non-calyceal input in the rat. To elucidate the function of this novel pathway, we investigated the connectivity and physiology of the mouse SLN, with particular focus on neuromodulation by group I metabotropic glutamate receptors (mGluRs). Viral tracing not only confirmed the SLN-MNTB pathway in mice, but also revealed that MNTB-projecting SLN neurons received their input from the ipsilateral auditory cortex. Physiological characterization of SLN neurons using whole-cell patch-clamp recordings showed that SLN neurons, unlike most other auditory brainstem neurons, were intrinsically highly excitable. Electrical stimulation of the fibre tracts located dorsal to the SLN, evoked small, slow AMPA receptor-mediated EPSCs in SLN neurons that readily summated temporally. Immunolabeling revealed a heterogeneous expression of mGluR1 and mGluR5 across SLN neurons. A subpopulation of SLN neurons exhibited spontaneous action potential firing at resting membrane potential. Pharmacological activation of group I mGluRs further increased spontaneous firing of SLN neurons. Probing for functional connectivity between SLN and the ipsilateral MNTB, fibre tracts dorsal and lateral to the MNTB were stimulated, eliciting primarily non-calyceal AMPA receptor-mediated EPSCs in MNTB neurons. These findings suggest that SLN output may provide a glutamatergic tonic drive to MNTB neurons, potentially modulating their temporal processing. KEY POINTS: MNTB receives a descending input from the ipsilateral auditory cortex via SLN. SLN neurons are highly excitable during development and into maturation, with a subset exhibiting spontaneous firing at resting membrane potential. Descending glutamatergic input to SLN is small and slow, and shows consistent temporal summation. Group I mGluRs further enhance spontaneous firing of SLN neurons and both mGluR1 and mGluR5 are expressed in the SLN. Descending ipsilateral projections to MNTB neurons primarily drive glutamatergic, non-calyceal inputs.