Development of excitatory synaptic transmission to the superior paraolivary and lateral superior olivary nuclei optimizes differential decoding strategies

Highlights

• The efficacy of excitation is developmentally strengthened in the SPON and LSO.

• High release probability gives rise to reliable excitation in the SPON.

• Broad stimulus–response output enables fast and flexible excitation in the LSO.

• These respective properties preserve coarse temporal and sound level information.

• This provides insight into the mammalian streaming of the acoustic cues.

Abstract

The superior paraolivary nucleus (SPON) is a prominent structure in the mammalian auditory brainstem with a proposed role in encoding transient broadband sounds such as vocalized utterances. Currently, the source of excitatory pathways that project to the SPON and how these inputs contribute to SPON function are poorly understood. To shed light on the nature of these inputs, we measured evoked excitatory postsynaptic currents (EPSCs) in the SPON originating from the intermediate acoustic stria and compared them with the properties of EPSCs in the lateral superior olive (LSO) originating from the ventral acoustic stria during auditory development from postnatal day 5 to 22 in mice. Before hearing onset, EPSCs in the SPON and LSO are very similar in size and kinetics. After the onset of hearing, SPON excitation is refined to extremely few (2:1) fibers, with each strengthened by an increase in release probability, yielding fast and strong EPSCs. LSO excitation is recruited from more fibers (5:1), resulting in strong EPSCs with a comparatively broader stimulus–response range after hearing onset. Evoked SPON excitation is comparatively weaker than evoked LSO excitation, likely due to a larger fraction of postsynaptic GluR2-containing Ca²⁺-impermeable AMPA receptors after hearing onset. Taken together, SPON excitation develops synaptic properties that are suited for transmitting single events with high temporal reliability and the strong, dynamic LSO excitation is compatible with high rate-level sensitivity. Thus, the excitatory input pathways to the SPON and LSO mature to support different decoding strategies of respective coarse temporal and sound intensity information at the brainstem level.

Introduction

The superior paraolivary nucleus (SPON) is a prominent mammalian auditory brainstem nucleus. Due to the high sensitivity of its neurons to abrupt sound transients and large fluctuations in sound amplitude over time (Kuwada and Batra, 1999, Behrend et al., 2002, Kulesza et al., 2003, Kadner and Berrebi, 2008, Felix et al., 2011, Felix et al., 2013), the SPON has been hypothesized to play a major role in processing natural sounds that are rhythmically modulated (Theunissen and Elie, 2014). The fact that the SPON is primarily driven by monaural sound stimulation (Kuwada and Batra, 1999, Kulesza et al., 2003) lends further support in favor of its involvement in the processing of communication sounds (Plomp, 1976, Culling et al., 2003). In contrast, the neighboring lateral superior olivary nucleus is known to process binaural sound cues, which are used to localize sound sources (Tollin, 2003). The underlying cellular mechanism for LSO sound processing is known to originate from integration of excitation from the anterior ventral cochlear nucleus (AVCN) and inhibition from the medial nucleus of the trapezoid body (MNTB) (Boudreau and Tsuchitani, 1968, Cant and Casseday, 1986, Sanes and Rubel, 1988, Wu and Kelly, 1992). Although the SPON has recently received increased attention, much less is known of how the inputs to its neurons contribute to sound processing compared to neighboring auditory nuclei.

SPON activity is characteristically triggered in vivo at the cessation of contralateral sound stimulation, generating an offset response (Kuwada and Batra, 1999, Behrend et al., 2002, Dehmel et al., 2002, Kulesza et al., 2003). This offset response has been linked to hyperpolarization-activated rebound spiking in SPON neurons in vitro (Felix et al., 2011, Kopp-Scheinpflug et al., 2011), triggered by feed-forward inhibition from the MNTB (Kuwabara et al., 1991, Kulesza et al., 2007, Kopp-Scheinpflug et al., 2011). In addition to the characteristic offset response, an onset response to contralateral sound stimulation has also been described for SPON neurons (Kuwada and Batra, 1999, Behrend et al., 2002, Dehmel et al., 2002, Felix et al., 2013), but despite the presence of a well-documented excitatory pathway from the posterior ventral cochlear nucleus (PVCN) to the contralateral SPON via the intermediate acoustic stria (IAS; Zook and Casseday, 1985, Friauf and Ostwald, 1988, Thompson and Thompson, 1991, Schofield, 1995, Saldaña et al., 2009), the physiological implications of this projection on SPON function have not been explored. While there have been reports of some SPON responses that are not monaural or do not have offset spiking (Behrend et al., 2002, Dehmel et al., 2002), we focused the current study on neurons with contralaterally-driven offset responses because they have been well characterized, are present in all species studied thus far (bat: Grothe, 1994; rabbit: Kuwada and Batra, 1999; gerbil: Behrend et al., 2002, Dehmel et al., 2002; rat: Kulesza et al., 2003, Kulesza et al., 2007, Kadner and Berrebi, 2008; mouse: Felix et al., 2011; 2012; Kopp-Scheinpflug et al., 2011), and possess distinct properties that make them well suited for processing the identity of natural sound (Kadner and Berrebi, 2008, Felix et al., 2011).

One important question is to what extent the excitatory transmission to the SPON is developmentally regulated. For instance, it is possible that SPON excitation has a more prominent role before hearing onset, at ages when glutamatergic depolarization has been shown to drive refinement of the input circuitry in the adjacent LSO (Gillespie et al., 2005, Noh et al., 2010). In order to characterize the physiological properties of the PVCN excitatory projection to the SPON, we used whole-cell patch-clamp recordings obtained in mouse brain slices to study synaptically evoked excitation during auditory development. In addition to describing the developmental properties of SPON excitation for the first time, we systematically compared these properties to the well-characterized LSO excitation (Sanes and Rubel, 1988, Sanes, 1993, Wu and Fu, 1998, Case et al., 2011, Alamilla and Gillespie, 2011, Lee et al., 2016).