Patterning of spontaneous action potentials in immature inner hair cells varies with cochlear location and is dependent on acetylcholine

Patterned spontaneous action potential (AP) activity occurs during critical periods of mammalian sensory system development and is hypothesized to drive the refinement of synaptic connections before the onset of sensory-induced activity (Katz, Shatz 1996 Science 274: 1133-8). Position dependent patterning of AP activity has been observed prior to the onset of hearing in chick auditory brainstem neurones (Lippe 1995 Brain Res 703: 205-13). It is likely that such activity is driven by AP firing in cochlear inner hair cells (IHCs) (Kros et al 1998 Nature 394: 281-4). It remains uncertain whether IHC AP activity is intrinsically generated or initiated by waves of ATP released from nearby supporting cells (Tritsch et al 2007Nature 450: 50-5). AP activity was investigated in IHCs of altricious rodents maintained at 35-37°C in perilymph-like extracellular solution using whole-cell current clamp and cell-attached voltage clamp recordings. We show that during the first postnatal week, AP activity is intrinsically generated by IHCs and its frequency and pattern differ as a function of position along the cochlea, with apical IHCs exhibiting bursting as opposed to more sustained firing in basal cells. The difference in pattern is likely to be determined by the efferent neurotransmitter ACh, which by fine-tuning the IHC’s resting membrane potential (Vm) is crucial for the bursting pattern present in apical IHCs. Endogenous extracellular ATP also contributes to maintaining the required Vm of both apical and basal IHCs via the activation of SK2 channels. We hypothesize that the difference in IHC firing pattern along the cochlea during the first postnatal week guides the functional differentiation of IHCs along the tonotopic axis (Johnson et al 2008 J Neurosci 28: 7670-8) and refines tonotopic maps along the auditory pathway before the onset of sensory experience (Kandler et al 2009 Nat Neurosci 12: 711-7).