# Transplantation of GABAergic Interneuron Progenitors Restores Cortical Circuit Function in an Alzheimer's Disease Mouse Model

## TL;DR

Transplanting GABAergic interneuron progenitors into a mouse model of Alzheimer's disease restored disrupted brain rhythms, suggesting stem cell therapy could help treat the disease.

## Contribution

Demonstrates that stem cell transplantation can restore cortical circuit function in an Alzheimer's disease model.

## Key findings

- Transplanted MGE progenitors matured into functional GABAergic interneurons in the host cortex.
- Donor interneurons rescued slow oscillation rhythms in the absence or presence of optogenetic stimulation.
- The study provides proof-of-concept for using stem cell therapy to treat Alzheimer's-related cortical impairments.

## Abstract

In addition to dementia, Alzheimer's patients suffer from sleep impairments and aberrations in sleep‐dependent brain rhythms. Deficits in inhibitory GABAergic interneuron function disrupt one of those rhythms, slow oscillation in particular, and actively contribute to Alzheimer's progression. The degree to which transplantation of healthy donor interneuron progenitors restores slow oscillation rhythm in young APP/PS1 mice is tested. Medial ganglionic eminence (MGE) progenitors are harvested from mouse embryos and transplanted them into host APP/PS1 mutant cortices. 3D light‐sheet and structured illumination microscopy revealed that transplanted MGE progenitors survived and matured into healthy interneurons. In vivo multiphoton calcium imaging and voltage‐sensitive dye imaging showed functional integration and slow oscillation rescue in the absence or presence of optogenetic stimulation. The work provides proof‐of‐concept evidence that stem cell therapy may serve as a viable strategy to rescue functional impairments in cortical circuits of APP/PS1 mice and potentially those of Alzheimer's patients.

Transplantation of medial ganglionic eminence (MGE) interneuron progenitors into APP/PS1 cortices restored the slow oscillation characteristic of Alzheimer's disease. Donor cells survived, migrated, and matured into functional GABAergic interneurons, forming synaptic connections. Donor cells integrated and rescued slow oscillation, providing proof‐of‐concept that stem‐cell therapy can restore cortical network function in Alzheimer's disease.