Calcium action potentials in hair cells pattern auditory neuron activity before hearing onset

The shape of the presynaptic action potential (AP) has a strong impact on neurotransmitter release. Because of the small size of most terminals in the central nervous system, little is known about the regulation of their AP shape during natural firing patterns in vivo. The calyx of Held is a giant axosomatic terminal in the auditory brainstem, whose biophysical properties have been well studied in slices. Here, we made whole-cell recordings from calyceal terminals in newborn rat pups. The calyx showed a characteristic burst firing pattern, which has previously been shown to originate from the cochlea. Surprisingly, even for frequencies over 200 Hz, the AP showed little or no depression. Current injections showed that the rate of rise of the AP depended strongly on its onset potential, and that the membrane potential after the AP (V after ) was close to the value at which no depression would occur during high-frequency activity. Immunolabeling revealed that Na v 1.6 is already present at the calyx shortly after its formation, which was in line with the fast recovery from AP depression that we observed in slice recordings. Our findings thus indicate that fast recovery from depression and an inter-AP membrane potential that minimizes changes on the next AP in vivo, together enable high timing precision of the calyx of Held already shortly after its formation.A ction potentials (APs) are followed by a period of decreased excitability called the refractory period. High-frequency firing thus requires special adaptations to minimize this refractory period and maintain AP stability. The changes in the AP waveform that occur at high firing frequencies are especially relevant in presynaptic terminals, where the shape of the AP critically controls calcium influx via voltage-dependent calcium channels, and thus transmitter release (1, 2). Following the AP, the membrane potential during the recovery period has a large influence on the speed of the recovery from inactivation of voltage-dependent sodium channels and deactivation of voltagedependent potassium channels, which are two major determinants of the refractory period (2). In some terminals, the AP is followed by a depolarizing afterpotential (DAP) (3-9), whereas in others a hyperpolarizing afterpotential (HAP) has been observed (10-14). The sign of this afterpotential depends on the resting potential (6,7,15), suggesting that the membrane potential following the AP (V after ) might be more important than the sign of the afterpotential.The calyx of Held is a glutamatergic axosomatic terminal whose biophysical properties have been well studied (16). Its many release sites enable it to act as an inverting relay synapse within the auditory brainstem that reliably drives its postsynaptic partner, a principal neuron in the medial nucleus of the trapezoid body (MNTB), even at firing frequencies >200 Hz (17). Shortly after its formation, around postnatal day 2 (P2) in rodents (18)(19)(20), it already fires in characteristic high-frequency bursts in vivo (21,22). In slice studi...

Section: Resultssupporting

confidence: 84%

“…Fourth, the terminals showed a characteristic firing pattern, consisting of minibursts with high firing frequencies ( Fig. 1D) (22,25,26). Its interval distribution resembled auditory nerve activity at this age (Fig.…”

Section: Resultsmentioning

confidence: 79%

Resistance to action potential depression of a rat axon terminal in vivo

Sierksma

Borst

2017

“…Spontaneous activity has been proposed to strengthen synaptic connections (22)(23)(24) and shape the tonotopic map in higher auditory nuclei. Indeed, AP firing should lead to glutamate-filled synaptic vesicle exocytosis and therefore support the propagation of information along the auditory pathway (3,10,11). Neighboring IHCs show synchronized firing patterns, which have been proposed to be the consequence of ATP released from the organ of Kölliker (6, 7).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, immature IHCs fire spontaneous and evoked action potentials (APs) until the onset of hearing (postnatal day 10 to postnatal day 12, P10-P12, in the mouse) (2)(3)(4)(5). Calcium AP firing in hair cells may refine synaptic connections along the ascending auditory pathway (6)(7)(8)(9), as a single AP triggers synaptic vesicle exocytosis, and convey information arising from hair cells to the higher auditory centers (3,10,11). APs from neonatal IHCs result mainly from the interplay between the inward calcium current carried by the voltage-gated calcium channel Cav1.3 subunit, a slow delayed rectifier potassium outward current, and the small conductance Ca 2+ -activated K + current SK2 (3,(12)(13)(14).…”

mentioning

confidence: 99%

Spatiotemporal pattern of action potential firing in developing inner hair cells of the mouse cochlea

Sendin

Bourien

Rassendren

et al. 2014

Inner hair cells (IHCs) are the primary transducer for sound encoding in the cochlea. In contrast to the graded receptor potential of adult IHCs, immature hair cells fire spontaneous calcium action potentials during the first postnatal week. This spiking activity has been proposed to shape the tonotopic map along the ascending auditory pathway. Using perforated patch-clamp recordings, we show that developing IHCs fire spontaneous bursts of action potentials and that this pattern is indistinguishable along the basoapical gradient of the developing cochlea. In both apical and basal IHCs, the spiking behavior undergoes developmental changes, where the bursts of action potential tend to occur at a regular time interval and have a similar length toward the end of the first postnatal week. Although disruption of purinergic signaling does not interfere with the action potential firing pattern, pharmacological ablation of the α9α10 nicotinic receptor elicits an increase in the discharge rate. We therefore suggest that in addition to carrying place information to the ascending auditory nuclei, the IHCs firing pattern controlled by the α9α10 receptor conveys a temporal signature of the cochlear development.auditory system | electrical activity | ATP receptor | acetylcholine receptor

“…Likewise, electrical activity arising in the periphery has been implicated in affecting the development of the central auditory system (40,41). To establish a link between afferent input and CN progenitor cells, we completely abolished afferent inputs by bilateral cochlear removal.…”

Section: Discussionmentioning

confidence: 99%

Transient, afferent input-dependent, postnatal niche for neural progenitor cells in the cochlear nucleus

Volkenstein

Oshima

Sinkkonen

et al. 2013

Significance The cochlear nucleus is the first central relay station for auditory signals from the cochlea. Like many other central relays for sensory systems, the cochlear nucleus features a period in newborn animals during which neuron survival and the number of synaptic contacts depends on afferent innervation from the periphery. This study extends this concept of postnatal plasticity toward neurogenesis. We identified neural progenitor cells in the cochlear nucleus whose proliferative capacity is controlled by interplay of several signaling pathways. When the cochlea was removed, the proliferating cell population diminished, suggesting that signals from the periphery are required to maintain this plasticity.