# PROJECT 1-Neural encoding based on lateral and medial entorhinal information processing streams in behaviorally-characterized aged rats

> **NIH NIH P01** · JOHNS HOPKINS UNIVERSITY · 2024 · $450,680

## Abstract

The hippocampus and medial temporal lobe are crucial components of the brain’s declarative memory system.
Extensive damage to these structures results in devastating and permanent loss of the ability to form new,
conscious memories of facts and personal experience. Aging is strongly associated with loss or change of
memory functions, in both normal aging and in neuropathological conditions. The lateral entorhinal cortex
(LEC) and medial entorhinal cortex (MEC) provide the large majority of medial temporal lobe input to the
hippocampus. The MEC appears to provide the hippocampus with a signal about the spatial location of an
organism. This signal is thought to act as a framework that allows the hippocampus to bind together the
individual components of an experience that occur at a moment in space and time. This framework allows the
hippocampus to form a coherent representation that is stored and later retrieved as an episodic memory. The
role of the LEC in this system has been less explored. The LEC may represent the individual components that
make up the content of an episodic memory. However, this role has not received as much experimental
investigation and validation compared to the role of MEC. Because the LEC is particularly vulnerable in the
early stages of age-related memory impairment, including Alzheimer’s Disease, it is imperative to understand
in detail the types of information represented in LEC and the neural coding mechanisms that underlie these
representations. Recent studies have provided two fundamental insights into LEC neural representations: (1)
LEC encodes a temporal context signal that allows the brain to represent and distinguish memories of events
that occur at different points in time; and (2) LEC represents the bearing of external items relative to the
observer in an egocentric frame of reference. The latter insight is consistent with the notion that LEC provides
the hippocampus with first-person information about the content of an episode, experienced and remembered
from an egocentric perspective. We hypothesize that the mnemonic deficits that mark early stages of age-
related cognitive decline and Alzheimer’s Dementia may result from the loss of normal temporal coding and
egocentric coding of the LEC inputs to the hippocampus. To test this hypothesis, we will determine whether
there are differences among young rats, aged rats without memory impairment, and aged rats with memory
impairment in these properties of LEC neurons. These experiments promise to provide crucial new data and
insights into how medial temporal lobe dysfunction produces the mild to severe memory impairments that can
range from minor inconvenience to devastating incapacity in aged individuals.

## Key facts

- **NIH application ID:** 10816455
- **Project number:** 5P01AG009973-29
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JAMES J KNIERIM
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $450,680
- **Award type:** 5
- **Project period:** 1997-09-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816455

## Citation

> US National Institutes of Health, RePORTER application 10816455, PROJECT 1-Neural encoding based on lateral and medial entorhinal information processing streams in behaviorally-characterized aged rats (5P01AG009973-29). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10816455. Licensed CC0.

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