Sunday, November 27, 2022 11/27/2022

The impact of transient developmental HL on corticostriatal eLTP expression during auditory learning.

Award Number: R01DC017163
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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PROJECT SUMMARY Auditory deprivation during the critical period of development can induce persistent changes along the entire auditory neuraxis, as well as, brain regions downstream of primary auditory cortex. One such brain region, the striatum, forms an excitatory circuit with the auditory cortex that drives decision-making. Recently, I have found that transient developmental HL leads to persistent changes in the excitatory synaptic strength, inhibitory synaptic strength, and cellular firing properties of gerbil auditory corticostriatal neurons. These changes involve receptors that mediate long-term potentiation. Thus the behavioral impairments that remain after recovery from developmental HL could in part be due to changes in the corticostriatal expression of excitatory long-term potentiation (eLTP) during task acquisition. The core hypothesis of this proposal is that auditory associative learning delay in HL subjects is caused by NMDA and GABA receptor mediated disruptions to eLTP expression along the auditory corticostriatal circuit. Aim one will assess how NMDA receptor and GABAA/B receptor function contributes to eLTP expression and auditory learning in the cortex and striatum. This will be accomplished by 1) carrying out whole-cell recording from corticostriatal brain slices in adult gerbils in the presence of NMDA or GABA receptor blockers during the induction of eLTP or 2) by infusing NMDA or GABA blockers directly into the cortex or striatum via micro cannula during auditory discrimination training. Aim two will assess how learning-induced changes to neural and synaptic properties in the cortex and striatum promote eLTP during task acquisition. This will be accomplished by 1) using in vitro whole-cell recordings from ACx L5 or striatum to measure the learning-induced changes to NMDA and GABA receptor function and how they alter the probability of eLTP expression during auditory discrimination learning or 2) by using in vivo electrophysiological recordings from ACx L5 or striatum to measure how changes to neural firing rates and patterns are correlated with increases in in vivo measures of eLTP during auditory discrimination learning. Aim three will ask how developmental HL-induced changes to the set point of synaptic strength or neural firing properties along the corticostriatal circuit affect eLTP expression during auditory learning. This will be accomplished by 1) using in vitro whole-cell recordings from ACx L5 or striatum of adult animals that experienced developmental HL to measure how the HL-induced changes to synaptic strength set points impact the learning-induced changes that drive eLTP expression during auditory discrimination learning or 2) by using in vivo electrophysiological recordings from ACx L5 or striatum of adult animals that experienced developmental HL to measure how HL-induced changes to neural firing properties impact the learning-induced changes that drive LTP during auditory discrimination learning. Together, this proposal will reveal how HL- induced changes to cellular and synaptic properties along the corticostriatal circuit interact with the learning-induced changes to cellular and synaptic properties that promote auditory learning.


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: 2022 ( Subtotal = $333,625 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	000	5	4/22/2022	NON-COMPETING CONTINUATION	$333,625


Issue Date FY: 2021 ( Subtotal = $317,937 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	002	4	3/23/2021	NON-COMPETING CONTINUATION	$333,094
2021	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	004	3	6/22/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$770
2021	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Research Related to Deafness and Communication Disorders	003	2	6/22/2021	NON-COMPETING CONTINUATION	-$770
2021	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	2	1/13/2021	NON-COMPETING CONTINUATION	-$256,163
2021	2020	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Research Related to Deafness and Communication Disorders	001	3	1/14/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$241,006


Issue Date FY: 2020 ( Subtotal = $336,813 )
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	2	3/16/2020	NON-COMPETING CONTINUATION	$336,813


Issue Date FY: 2019 ( Subtotal = $336,813 )
2019	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Research Related to Deafness and Communication Disorders	000	1	2/27/2019	NEW	$336,813


Grand Total All Awards = $1,325,188

Sum of Action Amount is $1,325,188;

Grand Total = $1,325,188

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The impact of transient developmental HL on corticostriatal eLTP expression during auditory learning.

Award Number: R01DC017163

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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