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Identification of inputs to unipolar brush cells and their roles in multisensory processing

Award Number: R00DC016905
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Identification of inputs to unipolar brush cells and their roles in multisensory processing - PROJECT SUMMARY / ABSTRACT The unipolar brush cell (UBC) is an excitatory interneuron cell type found in the dorsal cochlear nucleus (DCN) and vestibular cerebellum. UBCs are positioned within the circuit to amplify and prolong signals and likely play a major role in multisensory integration, sound source localization and cancellation of self-generated sounds. The UBC has a characteristic large dendritic brush that slows the diffusion of glutamate from the syn- apse and prolongs excitatory signals. Multisensory input is carried to UBCs by mossy fibers. The Trussell Lab has found that there are two types of UBCs- one responds to glutamate released from mossy fibers with an increase in firing (ON UBCs) and another that responds with a decrease in firing (OFF UBCs). I have recently discovered that in the vestibular cerebellum, ON UBCs receive direct primary afferent input from vestibular ganglion cells, whereas OFF UBCs receive indirect secondary input from vestibular nuclei. UBCs are also pre- sent in the dorsal cochlear nucleus (DCN), but their mossy fiber inputs are unknown. Aim 1 will use innovative tools and approaches to identify sources of input to UBC subtypes in DCN. Aim 2 will test the UBCs’ synaptic responses to those inputs. Aim 3, the R00 phase, will test the function and circuitry of UBCs in vivo. This proposal utilizes cutting-edge approaches under mentors and consultants with expertise in their use. In Aim 1, motivated by my findings in the vestibular system, I will test the hypothesis that in DCN primary sensory mossy fibers project to ON UBCs and secondary mossy fibers project to OFF UBCs. This Aim utilizes mouse genetics to target ON or OFF UBCs specifically, and monosynaptic transmission of pseudotyped rabies virus to identify presynaptic mossy fiber sources. In Aim 2 the pathways identified will be validated by expressing channelrhodopsin in the projecting sources and recording postsynaptic currents in UBCs using in vitro electro- physiology. Aim 3 during the R00 phase will combine the skills I have learned as a postdoc with my back- ground using in vivo electrophysiology. The function of UBCs in the DCN circuit will be tested by recording from the principal output (fusiform) neurons during optogenetic activation of ON or OFF UBCs. The role of UBCs in gating multisensory inputs to DCN will be tested by inhibiting ON or OFF UBCs optogenetically. This research will clarify the role of these fascinating excitatory interneurons in multisensory integration. Be- cause of UBCs’ potential role in the amplification of excitatory signals, this work may provide insights into an etiology of tinnitus.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Research Related to Deafness and Communication Disorders	000	5	4/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $249,000 )
2023	2023	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Research Related to Deafness and Communication Disorders	000	5	12/16/2022	NON-COMPETING CONTINUATION	$224,101
2023	2023	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Research Related to Deafness and Communication Disorders	001	5	1/14/2023	NON-COMPETING CONTINUATION	$24,899
														Subtotal = $249,000

Issue Date FY: 2022 ( Subtotal = $249,000 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Research Related to Deafness and Communication Disorders	000	4	12/14/2021	NON-COMPETING CONTINUATION	$224,100
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Research Related to Deafness and Communication Disorders	001	4	4/21/2022	NON-COMPETING CONTINUATION	$24,900
														Subtotal = $249,000

Issue Date FY: 2021 ( Subtotal = $277,110 )
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Research Related to Deafness and Communication Disorders	001	3	6/22/2021	EXTENSION WITH OR WITHOUT FUNDS	$28,110
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Research Related to Deafness and Communication Disorders	000	3	1/13/2021	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $277,110

Grand Total All Awards = $775,110

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Identification of inputs to unipolar brush cells and their roles in multisensory processing

Award Number: R00DC016905

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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