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Context-dependent plasticity of adult-born neurons

Award Number: R01DC018545
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Context-dependent plasticity of adult-born neurons - Olfactory information is first processed by the neural circuits in the olfactory bulb. It is now widely appreciated that the olfactory bulb circuit is modified in an experience-dependent manner. An especially dramatic example of plasticity in olfactory bulb circuits is adult neurogenesis, in which thousands of newly born neurons are incorporated into the bulbar circuitry as local inhibitory neurons every day throughout adulthood. The majority of these adult-born neurons (ABNs) become granule cells that provide inhibition through the spines at their apical dendrites onto the principal mitral/tufted cells. In this proposal, we will characterize the synaptic structural plasticity of ABNs in the olfactory bulb and investigate its context-specificity and mechanisms. Understanding the detailed mechanisms of context-specific plasticity would have an important impact on clinical disorders such as Alzheimer's disease, age-related dementia, and post-traumatic stress disorders. Our central hypotheses are that 1) ABNs increase the density of their apical dendritic spines during learning of an olfactory discrimination task but not during passive experience of the same odorants, and 2) this context-specificity of ABN plasticity is ensured by feedback projections from the piriform cortex to the olfactory bulb which increases dendritic activity of ABNs during task learning. Such a context-specific recruitment of ABN inhibition could provide the basis for stimulus-specific inhibition to promote the pattern separation of representations of task-relevant odorants. We will address these hypotheses by combining in vivo two-photon structural imaging, in vivo two- photon calcium imaging, behavioral task in head-fixed mice, and pathway-specific optogenetics. We have been pioneering the use of these techniques in studying the dynamics of olfactory bulb circuits (Kato et al. Neuron 2012, Kato et al. Neuron 2013, Boyd et al. Cell Reports 2015, Chu et al. Neuron 2016, Chu et al. eNeuro 2017). In particular, we will leverage on our recent study that showed that ABNs are uniquely required for the learning of fine olfactory discrimination (Li et al. eLife 2018). In Aim 1, we will investigate the age- and context- specificity of granule cell synaptic plasticity in vivo and test the hypothesis that young ABNs uniquely increase their spine density during learning. In Aim 2, we will examine the dendritic calcium activity of ABNs as a potential cellular mechanism regulating ABN dendritic plasticity. In Aim 3, we will address the role of feedback projections from the piriform cortex to the olfactory bulb as a potential circuit mechanism that ensures the context specificity of ABN plasticity. These aims represent a systematic approach to investigate the mechanisms of how behavioral context can affect the plasticity of an olfactory circuit.


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	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	5	6/16/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $445,436 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	002	5	5/3/2024	NON-COMPETING CONTINUATION	$39,363
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	003	5	5/3/2024	SUPPLEMENT FOR EXPANSION	$5,181
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	5	2/17/2024	NON-COMPETING CONTINUATION	$354,258
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	001	5	2/21/2024	SUPPLEMENT FOR EXPANSION	$46,634
														Subtotal = $445,436

Issue Date FY: 2023 ( Subtotal = $524,690 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	4	2/14/2023	NON-COMPETING CONTINUATION	$400,336
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	001	4	2/16/2023	SUPPLEMENT FOR EXPANSION	$124,354
														Subtotal = $524,690

Issue Date FY: 2022 ( Subtotal = $472,875 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	001	3	4/21/2022	NON-COMPETING CONTINUATION	$40,035
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	3	2/20/2022	NON-COMPETING CONTINUATION	$360,301
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	002	3	9/19/2022	SUPPLEMENT FOR EXPANSION	$72,539
														Subtotal = $472,875

Issue Date FY: 2021 ( Subtotal = $399,913 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	2	2/12/2021	NON-COMPETING CONTINUATION	$399,913
														Subtotal = $399,913

Issue Date FY: 2020 ( Subtotal = $392,375 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	1	2/21/2020	NEW	$392,375
														Subtotal = $392,375

Grand Total All Awards = $2,235,289

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Context-dependent plasticity of adult-born neurons

Award Number: R01DC018545

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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