The general goal of this project is to understand how information about sound is processed by the brain. The inferior colliculus (IC) is the main auditory structure in the midbrain. All information about sound must pass through the IC as it travels from the ear to the cerebral cortex. This project continues our effort to understand the cellular basis for function of the IC. Despite numerous studies, far too little is known about how microanatomy, neuronal specializations, and synaptic organization underlie auditory processing in the IC. There are two very different types of excitatory input on neurons in the IC. We have discovered that specialized """"""""calyx-like"""""""" axosomatic synapses occur on the large GABAergic neurons in IC. These synapses contain VGLUT2, a molecule that loads the transmitter glutamate into synaptic vesicles. These excitatory synapses are absent on excitatory neurons or smaller GABAergic neurons where dendritic excitatory synapses predominate. Two basic circuits in the IC are proposed. In one, large GABAergic IC neurons receive a dense, excitatory synaptic input on the cell body and proximal dendrites. The other circuit has smaller glutamatergic and GABAergic IC neurons with glutamatergic inputs only on dendrites. GABAergic neurons in IC are studied in two experiments. We will show: (1) the large GABAergic neurons project exclusively to the thalamus;(2) the GABAergic neurons with and without calyx-like inputs will differ in their firing patterns and intrinsic membrane properties. Excitatory inputs to IC are studied in experiments to reveal the structure and function of the VGLUT2 calyx-like input to the large GABAergic IC neurons (circuit 1). We will show: (3) segregated auditory brainstem neurons expressing VGLUT1 or VGLUT2 that project to IC;(4) VGLUT2 axosomatic synapse originates from a single source in the auditory brainstem, and that this specialized synapse comes from a single axon;and (5) the VGLUT2 axosomatic synapses on GABAergic neurons differ from other glutamate synapses in IC. Inhibitory Inputs. Brain circuitry in the IC is notable because the IC receives both inhibitory and excitatory inputs from the lower auditory brainstem. The excitatory inputs to the IC are segregated into functional zones, but it is not clear if inhibitory inputs also follow the same pattern. Here, in experiment 6, we will use auditory physiology with an uanesthetized rabbit preparation to relate the patterns of inhibitory input to neural responses in the IC. We will specifically test the hypothesis that the ICc domains have different patterns of inhibitory inputs.

Public Health Relevance

The inferior colliculus is important for normal hearing since it is a major part of the central auditory pathway and neurons from the auditory cortex to the cochlear nucleus send direct connections to the inferior colliculus. Pathology such as stroke or tumor in the inferior colliculus may contribute to deafness, hearing loss, or audiogenic seizures. The inferior colliculus is now the site of auditory midbrain implants to electrically stimulate the central auditory pathway in patients after surgical removal of the eighth nerve.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000189-31
Application #
8469022
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
1982-04-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
31
Fiscal Year
2013
Total Cost
$419,595
Indirect Cost
$147,131
Name
University of Connecticut
Department
Neurosciences
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
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
Ito, Tetsufumi; Hioki, Hiroyuki; Sohn, Jaerin et al. (2015) Convergence of lemniscal and local excitatory inputs on large GABAergic tectothalamic neurons. J Comp Neurol 523:2277-96
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
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
Ito, Tetsufumi; Bishop, Deborah C; Oliver, Douglas L (2015) Functional organization of the local circuit in the inferior colliculus. Anat Sci Int :
Ito, Tetsufumi; Oliver, Douglas L (2014) Local and commissural IC neurons make axosomatic inputs on large GABAergic tectothalamic neurons. J Comp Neurol 522:3539-54
Ono, Munenori; Oliver, Douglas L (2014) Asymmetric temporal interactions of sound-evoked excitatory and inhibitory inputs in the mouse auditory midbrain. J Physiol 592:3647-69
Ono, Munenori; Oliver, Douglas L (2014) The balance of excitatory and inhibitory synaptic inputs for coding sound location. J Neurosci 34:3779-92
Merchan, Miguel A; Saldana, Enrique; Oliver, Douglas L (2012) Auditory neuroanatomy: a sound foundation for sound processing. Front Neuroanat 6:48

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