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Molecular specification of dopaminergic neuron diversity

Award Number: R01EY033772
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Molecular specification of dopaminergic neuron diversity - PROJECT SUMMARY Dopamine is produced by a small but impactful subset of neurons in the eye and brain. Because this neuromodulator plays a critical role in a host of mental illnesses and diseases, it is vital to understand how dopamine neuron subsets are established and maintained. Our preliminary data show that the serine-threonine kinase LKB1 is required to restrict the number of dopaminergic neurons in the retina. In addition, we identify new dopaminergic cell subsets and show that LKB1 is cell-intrinsically required in inhibitory interneurons to modulate dopamine neuron diversity using molecular and neurogenetic approaches. This is a compelling result because factors that control the number and type of neurons that produce dopamine have remained elusive. To understand how LKB1 regulates dopamine neuron diversity, we have devised a strategy encompassing neural identity and connectivity mapping, cell-type specific intersectional genetic and viral strategies, molecular and biochemical studies, and functional analysis. We propose three aims. In Aim 1, we ask whether LKB1 is spatially and temporally sufficient to instruct dopamine neuron diversity by modulating this kinase in specific locations and at particular times. In Aim 2, we identify the mechanism through which LKB1 functions and test the hypothesis that LKB1-AMPK signaling plays a critical role. In Aim 3, we extend our analysis to the midbrain to test whether LKB1 is similarly required in this disease-relevant brain region to limit dopamine neuron diversity. Identifying a kinase pathway that precisely controls dopamine neuron diversity is surprising, so completing these aims will markedly advance our understanding of how dopaminergic neurons are endowed with their unique properties. In addition, these results will provide new therapeutic avenues for restoring dopamine production in the context of disease.


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 = $593,691 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	3	2/14/2025	NON-COMPETING CONTINUATION	$593,691
2025	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Vision Research	001	2	5/29/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $593,691

Issue Date FY: 2024 ( Subtotal = $640,354 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Vision Research	001	2	7/1/2024	SUPPLEMENT FOR EXPANSION	$46,664
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	2	2/7/2024	NON-COMPETING CONTINUATION	$593,690
														Subtotal = $640,354

Issue Date FY: 2023 ( Subtotal = $593,690 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Vision Research	000	1	1/27/2023	NEW	$593,690
														Subtotal = $593,690

Grand Total All Awards = $1,827,735

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Molecular specification of dopaminergic neuron diversity

Award Number: R01EY033772

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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