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Elucidating the Role of Dorsal Lateral Geniculate Nucleus Burst-Mode Firing in Retinal Inactivation Induced Recovery from Monocular Deprivation

Award Number: F31EY033996
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Amblyopia is a common disorder of visual system development, resulting in poor visual acuity in one eye. Though there has been much research to understand the pathophysiology of the disorder, treating older children and adults with amblyopia remains a challenge. Interestingly, there have been clinical reports suggesting gains in the visual acuity of the amblyopic eye may be possible in adults following removal of the normal eye due to injury or disease. Motivated by these clinical reports, our lab recently discovered that temporarily silencing the retina of the normal eye via intravitreal injection of the sodium channel blocker tetrodotoxin (TTX) is effective at promoting a recovery in visual acuity in both cat and mouse models of amblyopia. Amazingly, this treatment is effective in older, more treatment resistant animals and does not cause any penalty to the injected eye. By elucidating the mechanism by which retinal inactivation is promoting recovery from a period of amblyopic rearing in animal models, we have the potential to determine how to best exploit this mechanism for the treatment of human amblyopia. It was initially hypothesized that silencing the retina via TTX injection would result in reduced activity in the dorsal lateral geniculate nucleus (dLGN), because the dLGN relays activity from retina to cortex. Surprisingly, this turned out to be incorrect; in actuality, neurons in the dLGN exhibit more spontaneous bursting activity following retinal inactivation. The proposed project will focus on investigating the hypothesis that this increase in dLGN burst mode firing is the mechanism by which retinal inactivation drives recovery from amblyopic rearing. To investigate this hypothesis, we will first describe dLGN activity following retinal inactivation via TTX with the use of chronic unit recordings. dLGN bursting will then be pharmacologically blocked to determine whether dLGN bursting is necessary for TTX mediated recovery from amblyopic rearing. Finally, dLGN burst-like activity will be imposed via optogenetic manipulation in order to determine whether bursting is sufficient to drive recovery from a period of amblyopic rearing. By enhancing our understanding of the role of dLGN activity in retinal inactivation induced recovery from amblyopic rearing, this project has the potential to inform our future research and suggest novel clinical approaches for treating amblyopia. This project will be carried out in the lab of Dr. Mark Bear in the Brain and Cognitive Sciences Department (BCS) at the Massachusetts Institute of Technology (MIT). The Bear lab contains all required equipment for the proposed project. All necessary training regarding required laboratory techniques will be provided by senior lab members or through collaboration with other labs in BCS. The Bear lab, BCS, and MIT will offer quality scientific and professional development resources to facilitate a successful transition into the next stage of the applicant’s research career.


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: 2024 ( Subtotal = $47,694 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Vision Research	000	3	3/12/2024	NON-COMPETING CONTINUATION	$47,694
														Subtotal = $47,694

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Vision Research	000	2	3/8/2023	NON-COMPETING CONTINUATION	$47,694
														Subtotal = $47,694

Issue Date FY: 2022 ( Subtotal = $46,752 )
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Vision Research	001	1	3/22/2022	NEW	$0
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Vision Research	002	1	5/26/2022	NEW	$716
2022	2022	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Vision Research	000	1	3/22/2022	NEW	$46,036
														Subtotal = $46,752

Grand Total All Awards = $142,140

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Elucidating the Role of Dorsal Lateral Geniculate Nucleus Burst-Mode Firing in Retinal Inactivation Induced Recovery from Monocular Deprivation

Award Number: F31EY033996

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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