Development of the intrinsic synaptic circuits of the inferior colliculus

Active Project Grant Awarded Last action

Award ID
R01DC019814
Recipient
Awarding agency
Obligated
$9,003,065

Award facts

Completion date 95% complete
Place of performance
Pittsburgh, PA 15213, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The auditory midbrain (inferior colliculus, IC) is a hub and a major subcortical integration center in the central auditory pathway. Neurons in the IC are tuned to specific spectro-temporal features and are involved in the processing of communication sounds and speech. Abnormal sound-evoked or spontaneous IC activity has been associated with numerous central hearing dysfunctions including impaired speech perception, hyperacusis, and tinnitus. The spectro-temporal tuning of IC neurons arises from the integration of a multitude of ascending and descending inputs and an elaborated network of excitatory and inhibitory intrinsic synaptic connections between IC neurons. While the function and organization of external inputs to the IC are becoming increasingly understood, current understanding of the organization, physiology, and development of synaptic connections intrinsic to the IC is limited, hampering insight into their potential roles in IC function. To fill this knowledge GAP, we propose to address three specific aims. In aim 1 we will test the hypothesis that the central nucleus of the IC (cnic) contains two separate, functionally distinct, local networks arising from disc-shaped and stellate cells. We further hypothesize that the differentiation of these networks occurs after hearing onset requires normal patterns or levels of sound-evoked activity. To address these hypotheses, we will use laser scanning photostimulation with caged glutamate to map the location of neurons in the cnic that monosynaptically connect to identified cnic neurons in slices from control mice and from mice that were reared in pulsed white noise or have experienced temporary conductive hearing loss. In aim 2 we will test the hypothesis that the physiological properties of synaptic connections are distinct between the two intrinsic cnic networks and that their maturation depends on normal auditory experience. We will address this using simultaneous whole-cell recordings from identified neurons in slices from control mice and mice with a history of abnormal auditory experience. In aim 3 we will test the hypothesis that abnormal sound-evoked single unit responses in the cnic of mice with a history of abnormal auditory experience reflect abnormal intrinsic connections. We will address this by characterizing spectro-temporal responses properties of optogenetically identified glutamatergic and gabaergic cnic neurons in awake control mice and mice with a history of abnormal auditory experience and correlate the changes observed in in-vivo with changes in intrinsic networks characterized in-vitro. Results from the proposed project will provided novel insight into the organization, synaptic physiology, and development of intrinsic cnic circuits and their possible role in impaired sound processing in the cnic. This new information will be valuable for understanding the circuit changes in the cnic that contribute to the generation of central hearing deficits that are commonly observed in children that suffered from conductive hearing loss.

Transactions

Action Obligated Date
Amendment $56,875
Amendment $511,874
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Amendment $56,875
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Amendment $56,875
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Amendment $575,470
Amendment $575,470
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Amendment $592,160
Original award $592,160
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Subawards

Subrecipient Amount Awarded
College Of New Jersey Development of the intrinsic synaptic circuits of the inferior colliculus $18,021
College Of New Jersey $16,492
College Of New Jersey $16,011

Quick answers

Who received award R01DC019814?

R01DC019814 was awarded to University Of Pittsburgh - Of The Commonwealth System Of Higher Education by National Institute on Deafness and Other Communincation Disorders (National Institutes of Health) on February 8, 2022.

How much is award R01DC019814 worth?

$9,003,065 has been obligated on R01DC019814.

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