Investigating Homeostatic Plasticity in Alzheimer's Disease

Destabilised spontaneous activity is one of the earliest signs of pathology in Alzheimer's disease (AD) and is predicted to trigger aberrant molecular cascades that impair neural function and drive synapse loss. Destabilised spontaneous activity is characterised by periods of hyper- and hypo- neural spiking activity and has been reported in both human AD patients and multiple studies using mice that model certain features of AD. However, the underlying synaptic and molecular mechanisms that lead to the early emergence of destabilised spontaneous activity are unclear. Elucidation of these mechanisms offers an opportunity to both understand the earliest causes of synaptic vulnerability and identify novel targets for early intervention. Here, we propose to study the neuronal plasticity mechanisms that are thought to prevent destabilised activity in both the healthy brain and preclinical rodent models capturing key features of AD to better understand their role in disease