# Multisite analysis of hippocampal neuronal ensembles

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $527,296

## Abstract

PROJECT SUMMARY
 The hippocampus is a brain structure that is critical for normal learning and memory functions. One of the
first brain regions to deteriorate in Alzheimer's Disease is the hippocampal memory system, causing the
memory deficits that are among the first cognitive symptoms of the disease. To understand why hippocampal
damage causes such severe memory deficits, it is necessary to understand the basic computational functions
of this brain region. Much research on the hippocampus is derived from the dorsal part of the hippocampus of
rodents, whereas the largest part of the hippocampus in humans (i.e., the anterior hippocampus) corresponds
to the much-less studied ventral hippocampus in rodents. The ventral hippocampus subserves different
behavioral and cognitive functions than the dorsal hippocampus, in large part because the dorsal and ventral
parts of the hippocampus are connected to different brain regions. The specific aims of this project are to test
the hypothesis that that the dorsal, middle, and ventral parts of the hippocampus, although distinct in their
behavioral functions, share a common computational function that is performed on the varying types of input
representations received along this axis. Aim 1 will test the specific hypothesis that the computational gradient
of spatial pattern separation to pattern completion in the dorsal CA3 region is preserved across all levels of the
hippocampal dorsal-ventral axis. To generalize these results to cognitive functions more associated with the
ventral hippocampus, Aim 2 will test the hypotheses that (a) proximal CA3 performs a pattern separation
function on contextual and odor inputs, whereas distal CA3 performs a pattern completion/generalization
function on these inputs, and (b) this gradient is preserved across all levels of the dorsal-ventral axis. Finally, to
understand the nature of the inputs from the entorhinal cortex to the hippocampus along the dorsal-ventral
axis, Aim 3 will test the hypothesis that the allocentric spatial properties of the medial entorhinal cortex, and the
egocentric spatial properties of the lateral entorhinal cortex, are differentially controlled by local and global
frames of reference in regions that project to the dorsal hippocampus and the ventral hippocampus,
respectively. The results of these experiments will provide crucial knowledge about how the hippocampus
performs its mnemonic computations that support our abilities to remember the episodic experiences of our
daily lives, including their spatial, social, and emotional contents.

## Key facts

- **NIH application ID:** 10812779
- **Project number:** 2R01NS039456-24
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JAMES J KNIERIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $527,296
- **Award type:** 2
- **Project period:** 1999-12-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10812779

## Citation

> US National Institutes of Health, RePORTER application 10812779, Multisite analysis of hippocampal neuronal ensembles (2R01NS039456-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10812779. Licensed CC0.

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