. 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. Our experiments in the avian model system focus on the first central nervous system target of the auditory nerve, the cochlear nucleus angularis, which initiates the ascending pathways involved in localization using binaural sound level cues and spectrotemporal processing. Rapid adaptation is crucial for neural coding of complex sounds and scenes by implementing temporal filtering, dynamic range adaptation and generating noise-invariant signal representations. Dynamic range adaptation occurs when auditory neurons adjust their firing rate-level encoding depending on the statistics of the acoustic stimulation, shifting upward with louder sound distributions. Adaptive cellular processes such as short-term synaptic plasticity (activity-dependent alterations in synaptic weight), intrinsic firing rate adaptation (via ion channel inactivation or hyperpolarizing currents), and modulatory transmitter feedback via second messenger systems are all candidate mechanism for implementing intensity-related adaptation. Using a combination of in vitro physiology, modeling and in vivo recordings, we will investigate an intrinsic mechanism called threshold adaptation and its reliance on the inactivation of sodium channels. We also test the hypothesis that short-term synaptic plasticity contributes to solving the `dynamic range problem': how human can hear across many orders of intensity magnitude in behavioral experiments given the (formerly known) limited physiological range of nerve fibers. 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 research will provide new data on how acoustic information is transmitted from the auditory nerve to the first central relay in normal hearing, and thus can provide a reference for devices such as cochlear implants that stimulate the nerve directly. The emphasis on temporal envelope coding may also provide new information on disorders that may be related to disrupted temporal processing, such as age-related hearing loss or auditory neuropathy, which can lead to a common but disabling difficulty with understanding speech in noise.

Public Health Relevance

In human hearing, understanding speech in a noisy environment becomes a difficult task for many older listeners as well as for cochlear implant users. Our research investigates how stimulation of the auditory nerve translates into physiological activity in the brain stem target, the cochlear nucleus. Experiments on the dynamic activity of ion channels and synapses in the early auditory pathways will provide new insight into how sound intensity is transformed into perception.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC010000-08
Application #
9513923
Study Section
Auditory System Study Section (AUD)
Program Officer
Poremba, Amy
Project Start
2010-03-01
Project End
2021-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
8
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Maryland College Park
Department
Biology
Type
Earth Sciences/Resources
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
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
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
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
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