Our overall goal is to understand how activity may alter auditory signal processing in the inferior colliculus (IC), a critical auditory center in the midbrain. As the midbrain hub of the auditory pathway, the neurons in the central nucleus of the IC integrate different types of ascending auditory information. The IC also gates the information reaching the auditory cortex through direct excitation and direct inhibition of the medial geniculate body. The unique position of IC has made it a recent target for deep brain stimulation. However, little is known about how evoked activity, either acoustic or electrical, may alter information transmission in IC neurons. Synaptic inputs are critical in shaping the responses of IC neurons to sound. In the central nervous system, it is well known that the synapses may be modified, e.g. potentiated or depressed in an activity dependent manner. Synaptic plasticity may play an important role for learning & memory and the development of neural circuits. Although long term potentiation (LTP) and depression (LTD) exist in the IC, their role is unclear. They might shape the neuronal responses to sound based on recent activity in the auditory pathway in adults. One critical factor in synaptic plasticity is the relative timing between the pre- and post- spike activity. Spike Timing Dependent Plasticity (STDP) is a formal way of evaluating that relationship often inducing both LTP and LTD in the same neuron when a different temporal order is used. Our project will elucidate the character of STDP in the IC. Since both sound processing and STDP phenomena vary temporally in the same millisecond time range, STDP may be highly relevant for the synaptic processing of sound. Moreover, a distinct advantage of using STDP in the experimental study of synaptic plasticity is that the location of the plasticity is clear and is restricted to the pre- and/or post synaptic sites of the recorded neuron in the IC. Our main goal is to investigate how activity may change the sound evoked responses in the inferior colliculus in mice in vivo. For this purpose, we will record sound-evoked neural responses with either juxtacellular/cell-attached or whole cell in vivo recording techniques. We will use STDP to compare the response to sound before and after the neuron is trained by combining the sound evoked response with action potentials evoked by single-cell current injection (nano-stimulation). Separate experiments will investigate the effects of STDP on spectral (frequency) tuning to sound, temporal modulation of sound relevant for communication, and responses to binaural stimuli relevant to sound localization. In complementary experiments, we will use a brains slice preparation of IC to investigate whether STDP is the same in different neuron types. Specifically, we will test GABAergic and glutamatergic neurons in GAD67-GFP transgenic mice where GABAergic neurons are labeled. Generally, the IC and lower auditory centers are considered less 'plastic' than auditory cortex. Our project may change this view and reveal physiologically relevant activity-dependent changes in IC. Such knowledge may be essential to understand normal hearing and for therapy, training, rehabilitation after hearing loss.

Public Health Relevance

The ability of the central nervous system to change, that is neural plasticity, is critical to normal function and the recovery of function after injury in all eural systems including the auditory system. This project will provide basic science information about how the central auditory system reacts to abrupt changes in activity, and this is relevant to activity-dependent change in both normal hearing and after hearing loss disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DC013822-02
Application #
8957913
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Platt, Christopher
Project Start
2014-12-01
Project End
2017-11-30
Budget Start
2015-12-01
Budget End
2017-11-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Neurosciences
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
Ono, Munenori; Bishop, Deborah C; Oliver, Douglas L (2017) Identified GABAergic and Glutamatergic Neurons in the Mouse Inferior Colliculus Share Similar Response Properties. J Neurosci 37:8952-8964
Ono, Munenori; Bishop, Deborah C; Oliver, Douglas L (2016) Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain. Sci Rep 6:20757
Ono, Munenori; Ito, Tetsufumi (2015) Functional organization of the mammalian auditory midbrain. J Physiol Sci 65:499-506
Ayala, Yaneri A; Udeh, Adanna; Dutta, Kelsey et al. (2015) Differences in the strength of cortical and brainstem inputs to SSA and non-SSA neurons in the inferior colliculus. Sci Rep 5:10383
Choy Buentello, David; Bishop, Deborah C; Oliver, Douglas L (2015) Differential distribution of GABA and glycine terminals in the inferior colliculus of rat and mouse. J Comp Neurol 523:2683-97