A detailed understanding of the neurophysiological basis of hearing is fundamental to the understanding of human hearing impairment and the guidance of further development of the most successful prosthetic intervention to date, the cochlear implant. Yet we still lack a complete description of how sound information is processed at even the first central nervous system relay, the cochlear nucleus. Different aspects of sound are extracted from the auditory nerve spike trains and encoded via parallel neural pathways. While the coding of timing cues have been studied extensively, the processing of intensity cues remains unclear, especially relating to non-localization tasks such as sound recognition. We recently determined that the timing and intensity circuits in the cochlear nucleus are distinguished by the expression of different forms of short-term synaptic plasticity. In vitro studies have demonstrated that the intensity pathways exhibit a mixture of short-term facilitation and depression that allows the transmission of rate-encoded intensity information. In contrast, the short-term depression found in timing circuits creates a synaptic gain control that contributes to intensity-invariant coding of timing cues. We expand our investigation of intensity coding to spike trains in response to dynamic, amplitude modulated sounds, an important component of sound communication signals. The goal of this proposal is to identify the synaptic and cellular mechanisms that contribute to the encoding of sound intensity and establish their importance in the intact brain.
Aim 1 uses the avian (chick) cochlear nucleus slice preparation to investigate two synaptic enhancement mechanisms: short-term synaptic facilitation and the contribution of NMDA-receptor currents to synaptic integration. We use dynamic clamp to determine the input-output function of cochlear nucleus neurons.
Aim 2 investigates how dynamic stimuli like amplitude-modulated sounds are processed at auditory nerve synapses in the cochlear nucleus by measuring physiological synaptic responses to rate-modulated spike train inputs, using electrical stimulation and dynamic clamp.
In Aim 3, we will extend our in vitro short-term plasticity results to the intact cochlear nucleus with in vivo, intracellular recordings in the avian brainstem. Given the recent advances in the restoration of hearing using prosthetic devices that stimulate the auditory nerve, it is critical to understand how nerve activity is interpreted by the central nervous system. This proposal will provide new information on the transformation of auditory information which will help improve assisted-hearing devices and lead to a better understanding of normal hearing.

Public Health Relevance

Improved cochlear implant devices are a major goal of hearing research. Our experiments will further this goal by defining how electrical stimulation of the auditory nerve translates into physiological activity in the brainstem target, the cochlear nucleus. Examination of how modulations of sound intensity are coded by the brain will also provide new insight into the difficulties that the hearing impaired and cochlear implant patients have in understanding speech in noisy environments.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Auditory System Study Section (AUD)
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Miller, Roger
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University of Maryland College Park
Schools of Earth Sciences/Natur
College Park
United States
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Ahn, J; MacLeod, K M (2016) Target-specific regulation of presynaptic release properties at auditory nerve terminals in the avian cochlear nucleus. J Neurophysiol 115:1679-90
Ahn, J; Kreeger, L J; Lubejko, S T et al. (2014) Heterogeneity of intrinsic biophysical properties among cochlear nucleus neurons improves the population coding of temporal information. J Neurophysiol 111:2320-31
Fontaine, Bertrand; MacLeod, Katrina M; Lubejko, Susan T et al. (2014) Emergence of band-pass filtering through adaptive spiking in the owl's cochlear nucleus. J Neurophysiol 112:430-45
Bloom, S; Williams, A; MacLeod, K M (2014) Heterogeneous calretinin expression in the avian cochlear nucleus angularis. J Assoc Res Otolaryngol 15:603-20
Kreeger, Lauren J; Arshed, Arslaan; MacLeod, Katrina M (2012) Intrinsic firing properties in the avian auditory brain stem allow both integration and encoding of temporally modulated noisy inputs in vitro. J Neurophysiol 108:2794-809
MacLeod, Katrina M; Horiuchi, Timothy K (2011) A rapid form of activity-dependent recovery from short-term synaptic depression in the intensity pathway of the auditory brainstem. Biol Cybern 104:209-23
MacLeod, Katrina M (2011) Short-term synaptic plasticity and intensity coding. Hear Res 279:13-21
Carr, Catherine E; Macleod, Katrina M (2010) Microseconds matter. PLoS Biol 8:e1000405