# Functional interactions of the entorhinal cortex during systems consolidation

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $31,285

## Abstract

PROJECT SUMMARY
Dysfunction in the stability of long-term memories is a core symptom of many neuropsychiatric disorders,
including Alzheimer’s disease, major depression, and post-traumatic stress disorder. The process by which
newly formed memories are stabilized into more permanent storage is known as memory consolidation. The
hippocampus (HPC) has a well-established role in the initial formation and storage of memory. Over the course
of days-to-months, memory recall is thought to become increasingly dependent on cortical regions, such as the
anterior cingulate cortex (ACC). How memory is reorganized at the systems level between HPC and ACC
remains poorly understood. Recent studies implicate an intermediate brain region, the entorhinal cortex (EC),
as facilitating consolidation of memories. Disrupting the EC impairs the ability of new memories to be stored over
long durations. However, it remains unclear when and how EC may contribute to memory consolidation. We
hypothesize that EC is recruited at the time of learning to stabilize neurons and neural ensembles in ACC that
represent a learned association. This project will test this by utilizing methods of monitoring and manipulating
the dynamics of brain-wide circuits over extended periods of time through three specific aims. In aim one, we
will first develop a novel virtual-reality based contextual learning task in head-fixed mice, allowing us to probe
the learning and recall of memories throughout the duration of consolidation (weeks-to-months). The EC-ACC
projection will be selectively inhibited at various time points to quantify its role in remote memory recall. In aim
2, we will record bulk neural activity from HPC, EC, and ACC using chronically implanted optical fibers (fiber
photometry) to track interregional interactions and the emergence of neural correlates of memory during memory
consolidation. In aim 3, we will perform two photon calcium imaging in ACC throughout memory retrieval
including recent and remote time points. The EC-ACC projection will be selectively inhibited and the effect of this
circuit on neural representations of memory at remote time points will be quantified. This investigation will fill a
substantial gap in our understanding of systems consolidation and facilitate new insights into the distributed
dynamics of memory in psychiatric health and disease. The applicant’s career goal is to be an academic
physician-scientist with a research program aimed at bridging the gap between basic systems neuroscience
research and clinical treatments. He is pursuing MD-PhD training at Weill Cornell Medical College and The
Rockefeller University, and will develop research, scientific communication, and clinical expertise skills during
this fellowship.

## Key facts

- **NIH application ID:** 10765705
- **Project number:** 5F30MH129058-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Andrew Toader
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $31,285
- **Award type:** 5
- **Project period:** 2022-02-01 → 2024-05-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765705

## Citation

> US National Institutes of Health, RePORTER application 10765705, Functional interactions of the entorhinal cortex during systems consolidation (5F30MH129058-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10765705. Licensed CC0.

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