| First Author | Ngodup T | Year | 2024 |
| Journal | Elife | Volume | 12 |
| PubMed ID | 38197879 | Mgi Jnum | J:349019 |
| Mgi Id | MGI:7619170 | Doi | 10.7554/eLife.89520 |
| Citation | Ngodup T, et al. (2024) The Na(+) leak channel NALCN controls spontaneous activity and mediates synaptic modulation by alpha2-adrenergic receptors in auditory neurons. Elife 12 |
| abstractText | Cartwheel interneurons of the dorsal cochlear nucleus (DCN) potently suppress multisensory signals that converge with primary auditory afferent input, and thus regulate auditory processing. Noradrenergic fibers from locus coeruleus project to the DCN, and alpha2-adrenergic receptors inhibit spontaneous spike activity but simultaneously enhance synaptic strength in cartwheel cells, a dual effect leading to enhanced signal-to-noise for inhibition. However, the ionic mechanism of this striking modulation is unknown. We generated a glycinergic neuron-specific knockout of the Na(+) leak channel NALCN in mice and found that its presence was required for spontaneous firing in cartwheel cells. Activation of alpha2-adrenergic receptors inhibited both NALCN and spike generation, and this modulation was absent in the NALCN knockout. Moreover, alpha2-dependent enhancement of synaptic strength was also absent in the knockout. GABA(B) receptors mediated inhibition through NALCN as well, acting on the same population of channels as alpha2 receptors, suggesting close apposition of both receptor subtypes with NALCN. Thus, multiple neuromodulatory systems determine the impact of synaptic inhibition by suppressing the excitatory leak channel, NALCN. |
