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ER calcium handling, single cell processing, and neural circuit function in vivo

Award Number: R01EY036445
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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ER calcium handling, single cell processing, and neural circuit function in vivo - Summary Calcium is a critical second messenger in neurons, regulating neuronal processes from dendritic integration to synaptic transmission. The endoplasmic reticulum (ER) is the major intracellular calcium store in neurons, and aberrant ER calcium signaling is associated with many neurodegenerative disorders. However, it is unclear how ER calcium signaling regulates neuronal function and neural circuit stability. We aim to directly interrogate the link between ER calcium handling, single cell processing, and neural circuit function in vivo. To that end, we will take an imaging approach to simultaneously measure and manipulate physiological neuronal signals and ER calcium dynamics in the context of motion vision circuits in Drosophila. This versatile experimental system provides us with unique access to fundamental, understudied biological questions about the relationship between the ER and neuronal activity. First, the neurons that comprise Drosophila motion vision circuits exhibit a remarkable array of cytosolic calcium signals, reflecting their computational diversity. Our experimental system will allow us to investigate how calcium handling by the ER contributes to these diverse cytosolic calcium signals by comparing cytosolic and ER calcium signals across well-defined neuronal cell types in vivo. Second, neurons are extremely energetically demanding. We will leverage our in vivo imaging system to investigate the hypothesis that stimulus-evoked ER calcium signals allow neurons to upregulate ATP production in order to keep up with fluctuating energetic demands. Finally, tight control of cytosolic calcium concentration is critical for neuronal functions—including dendritic integration, synaptic plasticity, and neurotransmitter release—that control neural circuit activity and, ultimately, animal behavior. By conducting our experiments in neurons that perform specific computations critical for the function of well-defined motion vision circuits, we will be able to assess the consequences of ER manipulations not only on single cell processing, but also on large-scale neural circuit function and animal behavior. Altogether, we seek to integrate information across organizational scales—from molecules to neurons to neural circuits—to provide a mechanistic, molecular and cellular framework for understanding how ER calcium handling contributes to brain function and dysfunction.


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 = $404,926 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Vision Research	000	3	6/1/2026	NON-COMPETING CONTINUATION	$404,926
														Subtotal = $404,926

Issue Date FY: 2025 ( Subtotal = $404,926 )
2025	2025	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Vision Research	000	2	7/25/2025	NON-COMPETING CONTINUATION	$404,926
														Subtotal = $404,926

Issue Date FY: 2024 ( Subtotal = $404,926 )
2024	2024	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Vision Research	000	1	8/8/2024	NEW	$404,926
														Subtotal = $404,926

Grand Total All Awards = $1,214,778

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ER calcium handling, single cell processing, and neural circuit function in vivo

Award Number: R01EY036445

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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