The inferior colliculus (IC) is a major site for integration of virtually all ascending and descending auditory pathways, and many fundamental characteristics of IC neurons are profoundly shaped by their inhibitory inputs. A significant source of GABAergic inhibition to the IC originates from a brainstem circuit formed by the medial nucleus of the trapezoid body (MNTB) and the nearby superior paraolivary nucleus (SPON). The long-term goal of this research program is to clarify the functional role of the MNTB/SPON circuit in hearing. Our central hypothesis is that the MNTB/SPON circuit extracts and encodes auditory stimulus discontinuities, and that the output of this circuit contributes to temporal processing in the IC. The objectives of this application are i) to determine how MNTB and SPON neurons integrate their synaptic inputs to generate the output of this circuit, and ii) to examine the impact of the MNTB/SPON circuit's efferent projection on response properties of IC neurons.
Three Specific Aims, each focusing on a specific step along the pathway from the MNTB to the IC, are proposed.
Specific Aim 1 will directly examine the influence exerted by the MNTB/SPON circuit on sound processing in the midbrain, focusing primarily on the ability of IC neurons to detect gaps in tones, and to synchronize their responses to sinusoidally amplitude modulated tones. A dual recording configuration will be used to reversibly inactivate SPON neurons, while simultaneously recording from their postsynaptic targets in the IC.
In Aims 2 and 3, we will perform in-vivo recording studies to clarify the roles of inhibition and excitation in shaping the response properties of SPON and MNTB neurons to stimulus discontinuities. A multi-step, sequential protocol will be employed to systematically block specific neurotransmitter systems in order to reveal their individual contributions to single-unit responses as a whole. Comprehensive characterizations of each recorded cell will be performed. The acuity with which stimulus discontinuities are detected between closely placed sounds or components of sounds plays an important role in speech perception, and deficits in temporal processing are related to language impairment. Therefore, a better understanding of the function of the MNTB/SPON circuit in animal models will advance our knowledge of the neural basis for human speech comprehension.

Public Health Relevance

In the communication-based culture of humans, hearing loss and the resulting deficiencies in language confer social and economic disadvantages, and have tremendous impact on the quality of life. This research focuses on a prominent neural circuit of the mammalian brainstem, whose proposed function is to detect short interruptions in auditory signals;the proper encoding of such interruptions, or gaps, is particularly important for human speech comprehension. Knowledge of the neural representation of temporal structures, such as gaps, will contribute to the continued development of recently introduced auditory midbrain implants that substitute for lost auditory nerve function.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
West Virginia University
Schools of Medicine
United States
Zip Code
Gao, Fei; Kadner, Alexandra; Felix 2nd, Richard A et al. (2017) Forward masking in the superior paraolivary nucleus of the rat. Brain Struct Funct 222:365-379
Gao, Fei; Berrebi, Albert S (2016) Forward masking in the medial nucleus of the trapezoid body of the rat. Brain Struct Funct 221:2303-17
Felix 2nd, Richard A; Magnusson, Anna K; Berrebi, Albert S (2015) The superior paraolivary nucleus shapes temporal response properties of neurons in the inferior colliculus. Brain Struct Funct 220:2639-52
Felix 2nd, Richard A; Vonderschen, Katrin; Berrebi, Albert S et al. (2013) Development of on-off spiking in superior paraolivary nucleus neurons of the mouse. J Neurophysiol 109:2691-704
Felix 2nd, R A; Kadner, A; Berrebi, A S (2012) Effects of ketamine on response properties of neurons in the superior paraolivary nucleus of the mouse. Neuroscience 201:307-19
Viñuela, Antonio; Aparicio, M-Auxiliadora; Berrebi, Albert S et al. (2011) Connections of the Superior Paraolivary Nucleus of the Rat: II. Reciprocal Connections with the Tectal Longitudinal Column. Front Neuroanat 5:1
Felix 2nd, Richard A; Fridberger, Anders; Leijon, Sara et al. (2011) Sound rhythms are encoded by postinhibitory rebound spiking in the superior paraolivary nucleus. J Neurosci 31:12566-78
Saldaña, E; Aparicio, M-A; Fuentes-Santamaría, V et al. (2009) Connections of the superior paraolivary nucleus of the rat: projections to the inferior colliculus. Neuroscience 163:372-87
Kadner, A; Berrebi, A S (2008) Encoding of temporal features of auditory stimuli in the medial nucleus of the trapezoid body and superior paraolivary nucleus of the rat. Neuroscience 151:868-87
Kulesza Jr, Randy J; Kadner, Alexander; Berrebi, Albert S (2007) Distinct roles for glycine and GABA in shaping the response properties of neurons in the superior paraolivary nucleus of the rat. J Neurophysiol 97:1610-20