Unraveling the molecular players at the cholinergic efferent synapse of the zebrafish lateral line

FREIXAS, AGUSTÍN E. CARPANETO; SALATINO, LUCIA; GALLINO, SOFIA; PLAZAS, PAOLA V.; MOGLIE, MARCELO J.; DOMENE, SABINA; WEDEMEYER, CAROLINA; ELGOYHEN, ANA BELÉN; CASTAGNOLA, TAIS; MARCOVICH, IRINA; GOUTMAN, JUAN D.

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2021 vol. 41 p. 47 - 60

0270-6474

The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. LL responsiveness is modulated by efferent neurons that aid in distinguishing between external and self-generated stimuli, maintaining sensitivity to relevant cues. One component of the efferent system is cholinergic, the activation of which inhibits afferent activity. LL hair cells (HCs) share structural, functional, and molecular similarities with those of the cochlea, making them a popular model for studying human hearing and balance disorders. Because of these commonalities, one could propose that the receptor at the LL efferent synapse is a α9α10 nicotinic acetylcholine receptor (nAChR). However, the identities of the molecular players underlying ACh-mediated inhibition in the LL remain unknown. Surprisingly, through the analysis of single-cell expression studies and in situ hybridization, we describe that a9, but not the a10, subunits are enriched in zebrafish HCs. Moreover, the heterologous expression of zebrafish a9 subunits indicates that homomeric receptors are functional and exhibit robust AChgated currents blocked by a-bungarotoxin and strychnine. In addition, in vivo Ca2+ imaging on mechanically stimulated zebrafish LL HCs show that ACh elicits a decrease in evoked Ca2+ signals, regardless of HC polarity. This effect is blocked by both a-bungarotoxin and apamin, indicating coupling of ACh-mediated effects to small-conductance Ca2+-activated potassium (SKs) channels. Our results indicate that an α9-containing (α9∗) nAChR operates at the zebrafish LL efferent synapse. Moreover, the activation of α9∗ nAChRs most likely leads to LL HC hyperpolarization served by SK channels.