The Na+ leak channel NALCN controls spontaneous activity and mediates synaptic modulation by α2-adrenergic receptors in auditory neurons.
Elife
; 122024 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-38197879
ABSTRACT
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 α2-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 α2-adrenergic receptors inhibited both NALCN and spike generation, and this modulation was absent in the NALCN knockout. Moreover, α2-dependent enhancement of synaptic strength was also absent in the knockout. GABAB receptors mediated inhibition through NALCN as well, acting on the same population of channels as α2 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interneurônios
/
Neurônios
Limite:
Animals
Idioma:
En
Revista:
Elife
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos