Spontaneous activity in the developing auditory system

Abstract

Spontaneous electrical activity is a common feature of sensory systems during early development. This sensory-independent neuronal activity has been implicated in promoting their survival and maturation, as well as growth and refinement of their projections to yield circuits that can rapidly extract information about the external world. Periodic bursts of action potentials occur in auditory neurons of mammals before hearing onset. This activity is induced by inner hair cells (IHCs) within the developing cochlea, which establish functional connections with spiral ganglion neurons (SGNs) several weeks before they are capable of detecting external sounds. During this pre-hearing period, IHCs fire periodic bursts of Ca(2+) action potentials that excite SGNs, triggering brief but intense periods of activity that pass through auditory centers of the brain. Although spontaneous activity requires input from IHCs, there is ongoing debate about whether IHCs are intrinsically active and their firing periodically interrupted by external inhibitory input (IHC-inhibition model), or are intrinsically silent and their firing periodically promoted by an external excitatory stimulus (IHC-excitation model). There is accumulating evidence that inner supporting cells in Kölliker's organ spontaneously release ATP during this time, which can induce bursts of Ca(2+) spikes in IHCs that recapitulate many features of auditory neuron activity observed in vivo. Nevertheless, the role of supporting cells in this process remains to be established in vivo. A greater understanding of the molecular mechanisms responsible for generating IHC activity in the developing cochlea will help reveal how these events contribute to the maturation of nascent auditory circuits.

Fig. 1

Two models to explain how spontaneous bursts of activity could be induced in IHCs before hearing onset. The “IHC-inhibition” model (at left) proposes that IHCs are depolarized and therefore tend to fire Ca²⁺ spikes continuously. Periodic inhibition of IHCs by an external modulator such as acetylcholine (ACh) or adenosine triphosphate (ATP) would interrupt this firing, transforming continuous activity into burst firing. The “IHC-excitation” model (at right) proposes that IHCs are hyperpolarized and thus predominantly silent in the absence of an external stimulation. When ATP (* or another excitatory modulator) is spontaneously released from ISCs, IHCs are slowly depolarized, triggering a brief train of Ca²⁺ spikes. In both scenarios, the bursts of IHC Ca²⁺ spikes induce glutamate release and bursts of action potentials in SGNs that are subsequently carried to the auditory brainstem via the eighth nerve