Inhibitory interneuron transplants restore brain functions in an Alzheimer mouse model

Abstract

Alzheimer’s disease (AD) and other cognitive disorders result in neuronal hypersynchrony and altered oscillatory rhythmic activity, but the underlying mechanisms are poorly understood. The brain relies on inhibitory interneurons to regulate network excitability and oscillatory rhythms required for cognitive functions. We previously showed that impaired Nav1.1-expressing inhibitory interneurons contribute to memory deficits in a mouse model of familial AD (hAPPJ20 mice). Here, we address whether inhibitory interneuron transplants from the medial ganglionic eminence (MGE) can restore brain functions in hAPPJ20 mice. Nav1.1-overexpressing, but not wild-type, MGE interneuron transplants reduced network hypersynchrony, enhanced gamma oscillatory activity, and improved cognitive functions in hAPPJ20 mice. We conclude that interneuron transplants restore network stability and brain rhythms that support cognitive function in a familial AD mouse model.