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Changes in Hippocampal Coding of Very Large Spaces from Adulthood to Senescence

Award Number: R21AG101586
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Changes in Hippocampal Coding of Very Large Spaces from Adulthood to Senescence - There is currently an approximate 60% success rate in diagnosing Alzheimer’s disease (AD) using cognitive tests. New FDA approved blood tests testing for amyloid plaque byproducts could soon bring this number to 90%, among patients with cognitive deficits. AD will now be detected earlier, and will consequently be more likely to be treated effectively. As amazing as these new indicators might be, effective treatments will still require an understanding of how the disease progresses, and how it affects the prefrontal and hippocampal structures, on a case-by-case basis. The ventral hippocampus (vHPC) is in bi-directional interactions with both the prefrontal cortex and the dorsal hippocampus (dHPC) and is likely to be an early locus of cognitive dysfunction. The traditional view is that vHPC and dHPC, even though they are part of the same anatomical structure, may perform different functions and that vHPC is much less involved in spatial navigation than dHPC. We propose that this view emanate from the fact that most of the studies in spatial navigation were conducted in relatively small environments where the large place fields of vHPC are not functionally relevant, because they do not discriminate between spatial locations (low position information content). Based in part on these findings, very little attention has been placed on the role of vHPC in normal or abnormal aging. In this 2-year proposal, we aim to fill this gap by characterizing the role of dHPC and vHPC in very large environments where the large place fields of vHPC are likely to be functionally relevant to spatial navigation. We further hypothesize that the encoding of space at both levels of the structure will be related to the complexity of the tasks. We propose to test these ideas by contrasting the multi-field and multi-scale neural encoding by place cells and the behavior of the animals in two tasks with low (foraging) and high (multi-goal maze) cognitive loads respectively. To measure the complexity of the multi-goal mazes, we propose to use the quantitative tools of Space Syntax, a common framework in Architectural Sciences that is rarely used in Neuroscience, if at all. We also propose to sample hippocampal activity in animals with increasing amount of experience and training, as in human aging, throughout their life span, starting from young adulthood until senescence. Whether differences in encoding between ventral and dorsal levels vary with complexity and age are observed or not, this study will likely provide important information and motivation for further studies of this and related structures not only in the context of spatial navigation in complex environments, but also in the manner in which they differentially processes simple and complex memories. Altogether, this proposal will advance our understanding to the role of the longitudinal axis of the hippocampus in complex spatial information processing and its changes as subjects age. It will shed further light of the contribution of this axis, as a whole, into the deficits observed during AD, dementia or mild Cognitive Impairments in humans.


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 = $439,750 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Aging Research	000	1	5/5/2026	NEW	$439,750
														Subtotal = $439,750

Grand Total All Awards = $439,750

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Changes in Hippocampal Coding of Very Large Spaces from Adulthood to Senescence

Award Number: R21AG101586

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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