Temporal Coding by Cochlear Nucleus Bushy Cells in DBA/2J Mice with Early Onset Hearing Loss

Abstract

The bushy cells of the anterior ventral cochlear nucleus (AVCN) preserve or improve the temporal coding of sound information arriving from auditory nerve fibers (ANF). The critical cellular mechanisms entailed in this process include the specialized nerve terminals, the endbulbs of Held, and the membrane conductance configuration of the bushy cell. In one strain of mice (DBA/2J), an early-onset hearing loss can cause a reduction in neurotransmitter release probability, and a smaller and slower spontaneous miniature excitatory postsynaptic current (EPSC) at the endbulb synapse. In the present study, by using a brain slice preparation, we tested the hypothesis that these changes in synaptic transmission would degrade the transmission of timing information from the ANF to the AVCN bushy neuron. We show that the electrical excitability of bushy cells in hearing-impaired old DBA mice was different from that in young, normal-hearing DBA mice. We found an increase in the action potential (AP) firing threshold with current injection; a larger AP afterhyperpolarization; and an increase in the number of spikes produced by large depolarizing currents. We also tested the temporal precision of bushy cell responses to high-frequency stimulation of the ANF. The standard deviation of spikes (spike jitter) produced by ANF-evoked excitatory postsynaptic potentials (EPSPs) was largely unaffected in old DBA mice. However, spike entrainment during a 100-Hz volley of EPSPs was significantly reduced. This was not a limitation of the ability of bushy cells to fire APs at this stimulus frequency, because entrainment to trains of current pulses was unaffected. Moreover, the decrease in entrainment is not attributable to increased synaptic depression. Surprisingly, the spike latency was 0.46 ms shorter in old DBA mice, and was apparently attributable to a faster conduction velocity, since the evoked excitatory postsynaptic current (EPSC) latency was shorter in old DBA mice as well. We also tested the contribution of the low-voltage-activated K+ conductance (g (KLV)) on the spike latency by using dynamic clamp. Alteration in g (KLV) had little effect on the spike latency. To test whether these changes in DBA mice were simply a result of continued postnatal maturation, we repeated the experiments in CBA mice, a strain that shows normal hearing thresholds through this age range. CBA mice exhibited no reduction in entrainment or increased spike jitter with age. We conclude that the ability of AVCN bushy neurons to reliably follow ANF EPSPs is compromised in a frequency-dependent fashion in hearing-impaired mice. This effect can be best explained by an increase in spike threshold.

Conductive Hearing Loss Disrupts Synaptic and Spike Adaptation in Developing Auditory Cortex

“…Although it is clear that deafferentation perturbs cellular properties throughout the central auditory system (Kotak and Sanes, 1996;Vale and Sanes, 2000;Kotak et al, 2005;Walmsley et al, 2006;Wang and Manis, 2006), the effect of sound attenuation has not been established. Because there is considerable debate about the behavioral impact of conductive hearing loss alone (Feagans et al, 1987;Teele et al, 1990;Mody et al, 1999;Psarommatis et al, 2001;Roberts et al, 2002;Paradise et al, 2005), it is essential to establish whether or not central deficits occur.…”

“…In vivo studies have shown that temporal processing is disrupted by hearing loss, but they do not distinguish between changes that may occur in the brainstem (Wang and Manis, 2006) and those that occur at higher centers. Direct examination of the synaptic or biophysical properties that subserve temporal processing can be revealed by direct examination of a specific area of the auditory CNS.…”

“…However, it is well documented that developmental auditory deprivation leads to extensive changes in auditory processing (Sharma et al, 2002;Syka, 2002). The most direct measures of neuron physiology demonstrate that sensorineural hearing loss (SNHL) alters both membrane properties and synaptic transmission throughout the central auditory system (Kotak and Sanes, 1996;Francis and Manis, 2000;Sanes, 2000, 2002;Oleskevich and Walmsley, 2002;Vale et al, 2003;Kotak et al, 2005;Wang and Manis, 2006). In contrast, conductive hearing loss (CHL) only attenuates sound transmission to the inner ear, but does not compromise the cochlea.…”

Short-Term Synaptic Depression and Recovery at the Mature Mammalian Endbulb of Held Synapse in Mice

“…However, despite the presence of a primary-like peristimulus spike-time histogram to tone bursts in vivo, the spike patterns of a bushy cell may not faithfully reflect the presynaptic activity of a given ANF (Kopp-Scheinpflug et al 2002) due to several factors. These include the convergence of ANFs onto bushy neurons (Leao et al 2005;Liberman 1991;Nicol and Walmsley 2002;Rothman et al 1993;Ryugo and Parks 2003;Xu-Friedman and Regehr 2005a,b), the effects of inhibition from the dorsal cochlear nucleus (DCN) and superior olivary complex (Caspary et al 1994;Wickesberg and Oertel 1988), activitydependent modulation of presynaptic release probability (Brenowitz and Trussell 2001a;Turecek and Trussell 2001), and synaptic depression during high rates of activity (Oleskevich et al 2000;Wang and Manis 2006;Xu-Friedman and Regehr 2005b;Yang and Xu-Friedman 2008;Zhang and Trussell 1994). More recently, recordings from presumed AVCN spherical bushy cells in vivo have suggested that as many as 50% of ANF spikes may fail to drive bushy cells (Kopp-Scheinpflug et al 2002.…”

Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation

“…The calyx of Held synapses in the auditory brainstem do show synaptic depression and facilitation (reviewed in Xu et al, 2007), although apparently these effects are smaller in the cochlear nucleus of mature animals (Wu and Oertel, 1987;Brenowitz and Trussell, 2001). Relatively small effects are seen in bushy cells (Wang and Manis, 2006); in non-bushy cells, depression and facilitation seem to overlap, giving a small net effect (MacLeod et al 2007). In addition, there are important differences between in-vivo and slice experiments (Hermann et al, 2007).…”