# Targeting the Septohippocampal Circuit in Alzheimer's disease

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $33,868

## Abstract

PROJECT SUMMARY
Alzheimer’s disease is characterized by pathological protein aggregates comprised of β-amyloid
plaques and tau neurofibrillary tangles. Mainstream hypotheses highlight synaptic dysfunction
and eventual neuronal atrophy as culprits for symptoms such as mood disorders, cognitive
function, and impaired spatial learning and memory. The shortage of effective treatments
highlights the gap in etiologic understanding of AD progression. While deficits in glutamatergic
neurotransmission and atrophy of cholinergic forebrain neurons have been extensively studied,
GABAergic transmission remains poorly understood in the context of AD. A key subpopulation of
GABAergic neurons in the medial septum (MS-GABA) project exclusively to the hippocampus
where they contact local inhibitory interneurons to support theta rhythm, spatial learning and
memory, and adult neurogenesis. MS-GABA circuit dysfunction and degeneration is commonly
observed in mouse models but has not yet been investigated in the 3xtg-AD line, thought to
closely mimic AD progression. Circuit manipulation studies are emergent therapeutic strategies
in neurological disorders. Therefore, we propose the use of chemogenetics to modulate the
activity of the MS-GABA circuit in AD. We expect early MS-GABA stimulation to rebalance
glutamate and GABA within the hippocampus of 3xtg-AD mice and expect recovery in spatial
learning and memory deficits. These studies will facilitate identification of critical periods in
prodromal stages of AD and test a novel therapeutic intervention strategy during these stages.

## Key facts

- **NIH application ID:** 9911267
- **Project number:** 1F31AG066504-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Connor Wander
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,868
- **Award type:** 1
- **Project period:** 2020-09-08 → 2021-08-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9911267

## Citation

> US National Institutes of Health, RePORTER application 9911267, Targeting the Septohippocampal Circuit in Alzheimer's disease (1F31AG066504-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9911267. Licensed CC0.

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