# Chronic heart failure in forebrain circuit dementias

> **NIH NIH R03** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2021 · $148,000

## Abstract

ABSTRACT
Heart failure (HF) is a major health issue, arising as the end-stage manifestation of cardiac syndromes and is
the leading cause of hospitalization among seniors in the United States. Chronic HF is accompanied by
cognitive deficits arising from alterations to neural circuitry in the brain and predisposes individuals to the
development of vascular dementia and Alzheimer's disease. The primary objective of this proposal is to
characterize the alterations to forebrain neural pathways in a mouse model of chronic HF. The central
hypothesis of this proposal is that chronic HF results in a differential degeneration of corticothalamic versus
corticocortical pathways. This is expected to result in changes to functional connectivity in the forebrain and
underlie the progression of cognitive deficits in chronic HF. The specific aims of this project are to characterize
the alterations to the layer 5 corticothalamic versus layer 2/3 corticocortical pathways in a mouse model of
chronic HF by examining: 1) changes to the neuroanatomical connections of the layer 5 and layer 2/3 neurons
and 2) alterations to neurophysiological responses in higher-order thalamic nuclei and cortical areas mediated
by activation of pathways from these layers. The proposed experiments are expected to identify the changes
to forebrain functional connectivity mediated by these different pathways and guide our future investigations
aimed at directly linking alterations to these pathways with the cognitive deficits experienced in chronic HF and
ultimately restoring normal behavior in this model system. These experiments will have a positive impact by
illuminating the important role of the layer 5 corticothalamic pathways underlying the cognitive deficits following
chronic HF, which will lead to enhanced diagnostics and prospective treatments for this and related sequelae,
notably vascular dementia and Alzheimer's disease.

## Key facts

- **NIH application ID:** 10276214
- **Project number:** 1R03NS122892-01
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** CHARLES C LEE
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $148,000
- **Award type:** 1
- **Project period:** 2021-08-17 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276214

## Citation

> US National Institutes of Health, RePORTER application 10276214, Chronic heart failure in forebrain circuit dementias (1R03NS122892-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10276214. Licensed CC0.

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