Concurrent Maturation of Inner Hair Cell Synaptic Ca2+ Influx and Auditory Nerve Spontaneous Activity around Hearing Onset in Mice

Abstract

Hearing over a wide range of sound intensities is thought to require complementary coding by functionally diverse spiral ganglion neurons (SGNs), each changing activity only over a subrange. The foundations of SGN diversity are not well understood but likely include differences among their inputs: the presynaptic active zones (AZs) of inner hair cells (IHCs). Here we studied one candidate mechanism for causing SGN diversity-heterogeneity of Ca 2ϩ influx among the AZs of IHCs-during postnatal development of the mouse cochlea. Ca 2ϩ imaging revealed a change from regenerative to graded synaptic Ca 2ϩ signaling after the onset of hearing, when in vivo SGN spike timing changed from patterned to Poissonian. Furthermore, we detected the concurrent emergence of stronger synaptic Ca 2ϩ signals in IHCs and higher spontaneous spike rates in SGNs. The strengthening of Ca 2ϩ signaling at a subset of AZs primarily reflected a gain of Ca 2ϩ channels. We hypothesize that the number of Ca 2ϩ channels at each IHC AZ critically determines the firing properties of its corresponding SGN and propose that AZ heterogeneity enables IHCs to decompose auditory information into functionally diverse SGNs.

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

“…In the mammalian cochlea, it has been proposed that hair cells from the basal coil of the immature cochlea display more sustained activity (8). However, we show that IHCs from the basal coil fire APs in a bursting-like mode, making their activity pattern indistinguishable from that of apical cells, which is consistent with rhythmic activity in the developing auditory pathway (23,(25)(26)(27). The agreement between our measurements performed at room and physiological temperature exclude this parameter as a culprit of interstudy differences.…”

Adenomatous Polyposis Coli Protein Deletion in Efferent Olivocochlear Neurons Perturbs Afferent Synaptic Maturation and Reduces the Dynamic Range of Hearing

“…1b). In contrast, the summating potential (SP) arising presynaptically from the IHCs (Yuan et al, 2014) was unaffected by the targeted deletion (WT SP, 0.235 Ϯ 0.029 V; cKO SP, 0.197 Ϯ 0.034 V for 16 kHz and 80 dB SPL; p ϭ 0.418 unpaired t test).…”

“…The SR gradient is mirrored by complementary gradients in synaptic morphology. Low-SR and high-SR fibers contact opposite sides of the IHC: synapses on the pillar (high-SR) side have large glutamate receptor patches opposite small presynaptic ribbons, whereas synapses on the modiolar (low-SR) side exhibit smaller glutamate receptor patches opposite larger ribbons (Liberman, 1982;Liberman et al, 2011;Yin et al, 2014). Although the SR gradient is critical for dynamic range of the auditory periphery, little is known about mechanisms that underlie differentiation of these synaptic gradients.…”

“…Ribbon synapse number and function are refined throughout development by numerous mechanisms, including the following: transient and sustained innervation of neonatal IHCs and SGN dendrites, respectively, by efferent olivocochlear (OC) neurons; purinergic and neurotrophic signals from supporting cells; thyroid hormone; and differential influx of Ca 2ϩ into IHCs (Johnson et al, 2005;Sendin et al, 2007;Tritsch et al, 2007;Roux et al, 2011;Zuccotti et al, 2012;Wong et al, 2013Wong et al, , 2014. In the adult cochlea, OC-SGN synapses are required for maintenance of SR range and ribbon size gradients, particularly large modiolar ribbons, as shown by surgical de-efferentiation (Liberman, 1990;Yin et al, 2014).…”

“…In the adult cochlea, OC-SGN synapses are required for maintenance of SR range and ribbon size gradients, particularly large modiolar ribbons, as shown by surgical de-efferentiation (Liberman, 1990;Yin et al, 2014). Not yet defined are when and how, during development, ribbon-size gradients are generated, or the impact on cochlear function if they are not established.…”