The auditory system consists of ascending pathways that transmit information from the ear to the cortex, where sound is perceived, and descending pathways from the cortex that modulate the processing and flow of ascending information. The descending pathways play a role in a wide variety of functions, including selective attention, learning, frequency selectivity, sound localization, and discrimination of speech sounds. Recent work has shown close ties between the descending pathways and the brainstem cholinergic system. Acetylcholine has been implicated in many of the same auditory functions just listed as well as arousal and detection of novel stimuli. Understanding the various functions of the descending and cholinergic systems has been impeded by lack of information on the underlying neuronal circuitry. The present proposal will combine multi-labeling anatomical tracing techniques with multi-labeling immunohistochemistry to identify the components and synaptic organization of these circuits. The experiments will focus on the inferior colliculus, a part of the midbrain that is involved in pathways for auditory perception as well as numerous aspects of auditory-driven behavior. The results will provide a framework for interpreting physiological and behavioral experiments, and will provide essential data for designing more advanced experiments to examine both the functions of these pathways and to determine the underlying cellular mechanisms.

Public Health Relevance

Descending auditory pathways and the pathways that use acetylcholine as a neurotransmitter play critical roles in functions such as selective attention and discrimination of sounds in a noisy environment. Understanding and improving these functions is an important goal in persons with hearing loss, cochlear implants or various disorders such as autism or schizophrenia. The present proposal will answer important questions about the circuitry that underlies these functions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC004391-14
Application #
8616664
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
1999-07-01
Project End
2016-02-29
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
14
Fiscal Year
2014
Total Cost
$380,950
Indirect Cost
$133,580
Name
Northeast Ohio Medical University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
077779882
City
Rootstown
State
OH
Country
United States
Zip Code
44272
Mellott, Jeffrey G; Foster, Nichole L; Nakamoto, Kyle T et al. (2014) Distribution of GABAergic cells in the inferior colliculus that project to the thalamus. Front Neuroanat 8:17
Schofield, Brett R; Mellott, Jeffrey G; Motts, Susan D (2014) Subcollicular projections to the auditory thalamus and collateral projections to the inferior colliculus. Front Neuroanat 8:70
Foster, Nichole L; Mellott, Jeffrey G; Schofield, Brett R (2014) Perineuronal nets and GABAergic cells in the inferior colliculus of guinea pigs. Front Neuroanat 7:53
Schofield, Brett R; Motts, Susan D; Mellott, Jeffrey G et al. (2014) Projections from the dorsal and ventral cochlear nuclei to the medial geniculate body. Front Neuroanat 8:10
Nakamoto, Kyle T; Sowick, Colleen S; Schofield, Brett R (2013) Auditory cortical axons contact commissural cells throughout the guinea pig inferior colliculus. Hear Res 306:131-44
Nakamoto, K T; Mellott, J G; Killius, J et al. (2013) Analysis of excitatory synapses in the guinea pig inferior colliculus: a study using electron microscopy and GABA immunocytochemistry. Neuroscience 237:170-83
Nakamoto, Kyle T; Mellott, Jeffrey G; Killius, Jeanette et al. (2013) Ultrastructural examination of the corticocollicular pathway in the guinea pig: a study using electron microscopy, neural tracers, and GABA immunocytochemistry. Front Neuroanat 7:13
Mellott, J G; Motts, S D; Schofield, B R (2011) Multiple origins of cholinergic innervation of the cochlear nucleus. Neuroscience 180:138-47
Schofield, Brett R; Motts, Susan D; Mellott, Jeffrey G (2011) Cholinergic cells of the pontomesencephalic tegmentum: connections with auditory structures from cochlear nucleus to cortex. Hear Res 279:85-95
Motts, S D; Schofield, B R (2011) Cholinergic cells in the tegmentum send branching projections to the inferior colliculus and the medial geniculate body. Neuroscience 179:120-30

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