Purinergic Signaling Controls Spontaneous Activity in the Auditory System throughout Early Development

BABOLA, TRAVIS A.; LI, SALLY; WANG, ZHIRONG; KERSBERGEN, CALVIN J.; ELGOYHEN, ANA BELÉN; COATE, THOMAS M.; BERGLES, DWIGHT E.

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Lugar: Washington; Año: 2021 vol. 41 p. 594 - 612

0270-6474

Spontaneous bursts of electrical activity in the developing auditory system arise within the44 cochlea prior to hearing onset and propagate through future sound processing circuits of the45 brain to promote maturation of auditory neurons. Studies in isolated cochleae revealed that this46 intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs),resulting in activation of purinergic autoreceptors, K+ 47 efflux and subsequent depolarization of48 inner hair cells (IHCs). However, it is unknown when this activity emerges or whether different49 mechanisms induce activity during distinct stages of development. Here we show that50 spontaneous electrical activity in mouse cochlea from both sexes emerges within ISCs during51 the late embryonic period, preceding the onset of spontaneous correlated activity in IHCs and52 spiral ganglion neurons (SGNs), which begins at birth and follows a base to apex developmental53 gradient. At all developmental ages, pharmacological inhibition of P2Y1 purinergic receptors54 dramatically reduced spontaneous activity in these three cell types. Moreover, in vivo imaging55 within the inferior colliculus revealed that auditory neurons within future isofrequency zones56 exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased57 progressively during the postnatal prehearing period, yet remained dependent on P2RY1.58 Analysis of mice with disrupted cholinergic signaling in the cochlea indicate that this efferent59 input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the60 auditory system uses a consistent mechanism involving ATP release from ISCs and activation61 of P2RY1 autoreceptors to elicit coordinated excitation of neurons that will process similar62 frequencies of sound