Cell‐type specific alterations in intrinsic excitability and neurotransmission in short‐term virally induced model of Alzheimer’s Disease

Alzheimer’s Disease (AD) is a neurodegenerative cascade resulting in neuronal dysfunction and memory loss, classically characterized by the deposition of amyloid plaques throughout the brain. Although deposition of these proteins correlates with cognitive loss in AD, these aggregates may not be causally related to initial neuronal and circuit pathology in AD. Interestingly, evidence in AD patients and mouse models has reported cortical circuit hyperexcitability prior to plaque pathology. The cell and molecular mechanisms underlying hyperexcitability in early‐stage AD remain unclear. In healthy brains, normal circuit operations are maintained through a fine‐tuned balance between excitatory (pyramidal) and inhibitory neuron activity. In several APP‐expressing mouse models, pyramidal and inhibitory neuron physiology are differentially affected and also evolve with disease severity. However, these parameters have not been explored in an adult‐onset APP model.