Wednesday, October 1, 2025 10/1/2025

Functional properties of amacrine cells in the mammalian retina

Award Number: R01EY032965
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Functional properties of amacrine cells in the mammalian retina - PROJECT SUMMARY This project proposes to study the roles of specific amacrine cells (ACs) in the visual signal processing performed by the mammalian retina. Electrophysiological recordings of light evoked activity will be made from ACs, ganglion cells (GCs), and bipolar cells in intact in vitro whole- mount and slice preparations of mouse retina maintained at photopic adaptation levels. The functional properties of the cells will be probed using images projected onto the photoreceptors through the microscope objective. Patch-clamp recordings from amacrine and ganglion cell somas will be performed to measure the stimulus-evoked postsynaptic currents, postsynaptic potentials, and spiking responses. The project focusses on the elucidating the synaptic mechanisms underlying the receptive field properties of 3 genetically labelled amacrine cell types. Aims 1 and 2 examine the functional properties of two types of amacrine cells, so called NOS-1 and NOS-2 amacrine cells, which are identified by their expression of nitric-oxide synthase (NOS). Aim 1 will test the hypothesis that the NOS-1 ACs are key interneurons for controlling the strength of surround antagonism in GCs at scotopic light levels and that they exert their effects via GABAergic synaptic connections to AII ACs. We will make dual recordings between the NOS- 1 ACs and specific types of GCs, to directly test for indirect synaptic connections consistent with the proposed circuit. Aim 2 will examine the role of NOS-2 ACs in conferring motion-sensitivity to specific type of small-field GCs in the mouse. We will use optogenetic stimulation of ChR2 expressing NOS ACs to identify the postsynaptic targets. The postsynaptic targets will be identified morphologically and physiologically and inputs arising from NOS-2 ACs will be confirmed by paired recordings. Aim 3 focuses on a novel amacrine cell type that is one of 2 AC types that can be identified by their expression of the gene Gbx2. We will focus on the Gbx2+ ACs that stratify in sublamina 3 (S3) of the inner plexiform layer. The S3-Gbx2+ ACs are highly unusual because they appear to express none of the conventional inhibitory or excitatory neurotransmitters, indicating that they represent novel populations of so-called non-GABAergic, non-glycinergic (nGnG) ACs. Preliminary data show that these nGnG ACs are tracer coupled to bipolar cells. We will quantify the spatio-temporal receptive field properties of these nGnG S3- Gbx2+ ACs and will test the hypothesis that they make output via electrical synapses with bipolar cells. To do so, we will make patch-clamp recordings from cone bipolar cells in slice and measure depolarizing responses elicited by optogenetic stimulation (ChR2 expression) of the S3-Gbx2+ ACs. Overall, the results will reveal the functional properties and connectivity of the three AC types and will determine their roles in visual processing in the retina.


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 = $400,884 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	4	3/27/2025	NON-COMPETING CONTINUATION	$400,884
														Subtotal = $400,884

Issue Date FY: 2024 ( Subtotal = $400,884 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	3	3/29/2024	NON-COMPETING CONTINUATION	$400,884
														Subtotal = $400,884

Issue Date FY: 2023 ( Subtotal = $400,884 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	2	4/3/2023	NON-COMPETING CONTINUATION	$400,884
														Subtotal = $400,884

Issue Date FY: 2022 ( Subtotal = $400,884 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	1608 4TH ST STE 201	BERKELEY	CA	94710	ALAMEDA	USA	Vision Research	000	1	4/1/2022	NEW	$400,884
														Subtotal = $400,884

Grand Total All Awards = $1,603,536

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Functional properties of amacrine cells in the mammalian retina

Award Number: R01EY032965

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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