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Cross modal plasticity following loss of vision at different developmental stages: Cortical function, connections and compensatory behavior

Award Number: R01EY034303
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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A distinguishing feature of the mammalian neocortex is its remarkable ability to change over a lifetime, particularly during early development. The development of cortical fields and their connections is highly dependent on the incoming sensory inputs they receive from the various sensory organs, such as the eyes and the skin. This input, together with the unique combinations of sensory information available in the environment shapes the neocortex to generate optimal behavior. We know from previous studies in our own laboratory that very early loss of input from the eyes leads to massive changes in the brain, such that all of what would normally be the primary visual cortex (V1) contains neurons that respond to somatosensory and auditory stimulation. This reorganized V1 receives ectopic input from thalamic nuclei and cortical fields associated with somatosensory and auditory processing. The current proposal addresses several fundamental questions raised by these previous findings: 1) How does the age of onset of blindness differentially impact cortical connectivity? 2) What are single-neuron response properties in reorganized V1 and S1, and does age of blindness onset impact these properties? 3) What is the relationship between functional and anatomical changes in V1 and S1 and compensatory behaviors mediated by the spared sensory systems? Our animal model, the short-tailed opossum, is highly altricial at birth (equivalent to embryonic day 11 in the mouse), allowing ex utero manipulations to the nervous system at developmental time points that would be in utero in other mammals. In these experiments, bilateral enucleations will be made at specific developmental milestones: 1) Prior to the onset of spontaneous activity in the retina, before retinal ganglion cells have reached their subcortical targets, and before thalamocortical axons have innervated the neocortex; 2) When spontaneous activity in the retina is present and retinogeniculate and thalamocortical axons have innervated their targets; 3) Just after eye opening, when sensory driven activity in the retina is present and thalamocortical and corticocortical connections have formed. Following enucleations, animals will be assessed at several different time points. These studies are novel in scope in that they interrogate how the of age of vision loss affects the reorganization of brain circuits and behavior, and if functional and anatomical changes to the neocortex are linked to compensatory behavior. These data can direct therapeutic interventions (e.g. tactile training based behavior), and even allow predictions for behavioral outcomes following retinal implants or gene targeted therapies performed at different ages.


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 = $370,843 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Vision Research	000	3	6/28/2024	NON-COMPETING CONTINUATION	$370,843
														Subtotal = $370,843

Issue Date FY: 2023 ( Subtotal = $370,899 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Vision Research	000	2	7/10/2023	NON-COMPETING CONTINUATION	$370,899
														Subtotal = $370,899

Issue Date FY: 2022 ( Subtotal = $371,780 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Vision Research	000	1	7/15/2022	NEW	$371,780
														Subtotal = $371,780

Grand Total All Awards = $1,113,522

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Cross modal plasticity following loss of vision at different developmental stages: Cortical function, connections and compensatory behavior

Award Number: R01EY034303

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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