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Piriform cortex: sequential developmental events

Award Number: R01DC013791
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: 12/01/2014
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Piriform cortex: sequential developmental events - Project Summary – Abstract The perception of odors begins in the olfactory epithelium when odorant ligands bind to molecular receptors expressed on the cilia of the olfactory sensory neurons, each of which expresses only 1 of ~1200 candidate receptors. As the sensory neuron axons exit the epithelium they progress over the surface of the olfactory bulb and all of the axons coming from neurons expressing the same odorant receptor converge into only 2/3 glomeruli/olfactory bulb. However, the convergence and discrete circuitry of the olfactory bulb is not apparent in piriform cortex (PCX), at least grossly. Afferent projections to piriform appear divergent and broadly distributed. Moreover, in contrast to the more widely studied neocortex, the 3-layer piriform paleocortex does not exhibit a definitive columnar structure, leaving open the question of whether principles learned from neocortex can be applied to understanding piriform. Most of what we know of the neuronal and synaptic organization of piriform has come from early studies of rat and opossum, that while important did not benefit from contemporary genetic and molecular tools. The mouse, which has emerged as the dominant mammalian model for studies of the olfactory epithelium and bulb, has benefited immeasurably from these new tools. However, there are few examples of the application of contemporary genetic and molecular methods to studies of mouse piriform cortex. We remain woefully ignorant of the most fundamental features of mouse piriform cortex When do synapses first appear in mouse PCX and when do they achieve laminar segregation? What is the organization of the ipsi- and contralateral association axons that likely contribute to the cortical coding of odors in ensembles of neurons? What are the molecular mechanisms/transcription factors underlying the fate and specificity of PCX neurons/structure? To begin addressing these significant gaps in our knowledge we are proposing 3 specific aims: Aim 1 addresses the emergence of synaptic circuits in PCX and tests the hypothesis that it occurs in a spatio-temporal format that distinguishes the laminar specificity of circuits. Aim 2 addresses the PCX associational connectome, both ipsilateral and contralateral via the anterior commissure. Aim 3 tests the spatiotemporal expression of transcription factors (TFs) that we hypothesize are important in establishing PCX pyramidal neuron identity and contributions to the association axon network in PCX. Selective TFs will be knocked out using CRISPR to determine their role at a more granular level. Collectively these innovative studies will provide new insight into the mechanisms regulating the organization of PCX and the foundations of odor coding in PCX.


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: 2026 ( Subtotal = $418,750 )
2026	2026	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	10	2/23/2026	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2025 ( Subtotal = $418,750 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	9	3/12/2025	NON-COMPETING CONTINUATION	$376,875
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	001	9	5/9/2025	NON-COMPETING CONTINUATION	$41,875
														Subtotal = $418,750

Issue Date FY: 2024 ( Subtotal = $418,750 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	8	3/29/2024	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2023 ( Subtotal = $418,750 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	7	3/25/2023	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2022 ( Subtotal = $418,750 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	6	3/9/2022	COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2021 ( Subtotal = -$1,400 )
2021	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	5	6/7/2021	NON-COMPETING CONTINUATION	-$1,400
														Subtotal = -$1,400

Issue Date FY: 2019 ( Subtotal = $353,813 )
2019	2019	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	5	2/8/2019	NON-COMPETING CONTINUATION	$353,813
														Subtotal = $353,813

Issue Date FY: 2018 ( Subtotal = $353,813 )
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	001	4	4/4/2018	NON-COMPETING CONTINUATION	$35,382
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	4	11/9/2017	NON-COMPETING CONTINUATION	$318,431
														Subtotal = $353,813

Issue Date FY: 2017 ( Subtotal = $353,813 )
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	001	3	5/24/2017	NON-COMPETING CONTINUATION	$35,382
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	3	11/2/2016	NON-COMPETING CONTINUATION	$318,431
														Subtotal = $353,813

Issue Date FY: 2016 ( Subtotal = $353,813 )
2016	2016	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	001	2	1/7/2016	NON-COMPETING CONTINUATION	$35,382
2016	2016	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	2	10/27/2015	NON-COMPETING CONTINUATION	$318,431
														Subtotal = $353,813

Issue Date FY: 2015 ( Subtotal = $353,813 )
2015	2015	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Research Related to Deafness and Communication Disorders	000	1	10/27/2014	NEW	$353,813
														Subtotal = $353,813

Grand Total All Awards = $3,861,415

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Piriform cortex: sequential developmental events

Award Number: R01DC013791

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: 12/01/2014

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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