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.

Hair Cell Mechanotransduction Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the Auditory System

“…In the auditory system, brain stem circuitry shows sensory-input independent activity coincident with structural and functional maturation (Kandler et al, 2009; Kandler and Gillespie, 2005; Tritsch and Bergles, 2010; Tritsch et al, 2007; Wang et al, 2015). Despite the immaturity of ribbon synapses at early postnatal stages, IHCs excite SGNs through activation of their glutamate receptors (Beutner and Moser, 2001; Glowatzki and Fuchs, 2002; Johnson et al, 2005; Robertson and Paki, 2002; Tritsch and Bergles, 2010; Wang and Bergles, 2015). Inner supporting cells are implicated in the generation of spontaneous activity in the cochlea (Tritsch et al, 2007; Wang et al, 2015), but the involvement of IHC in this process are less well understood.…”

Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea

“…The timing of the switch is concurrent with a transformation in the IHC voltage signals, from all-or-nothing action potentials to graded receptor potentials. In the neonate, IHCs exhibit Ca 2+ -dependent action potentials that drive spontaneous firing in the auditory nerve; these signals may contribute to the refinement and maintenance of tonotopic maps in the auditory brainstem (288) (296). The action potentials disappear in the adult, when sound-evoked receptor potentials that are graded with stimulus intensity first appear (186).…”

Spontaneous Activity of Cochlear Hair Cells Triggered by Fluid Secretion Mechanism in Adjacent Support Cells

“…In the developing auditory system, neurons exhibit periodic bursts of action potentials prior to hearing onset, a phenomenon that is conserved from birds to mammals (Wang and Bergles, 2015). Prior studies have shown that ablation of the cochlea or peripheral block of action potentials in the auditory nerve abolishes burst firing in central auditory centers (Lippe, 1994; Tritsch et al, 2010a), indicating that spontaneous activity originates within the developing cochlea.…”