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Lost in Translation: Understanding the Silent Phase of Alzheimer’s Disease
Inna Slutsky
Tel Aviv University, Israel
How neurons and neural networks, composed from highly dynamic molecules with relatively short half-lives, maintain stable firing properties remains one of the most fascinating questions in neuroscience. Since Claude Bernard's time, scientists have sought to unravel the fundamental principles and mechanisms governing the homeostasis of neuronal circuits. In this talk, I will explore the molecular, cellular, and network-level mechanisms that regulate homeostatic activity set-points in hippocampal circuits. Additionally, I will propose a hypothesis suggesting that activity dyshomeostasis in cortico-hippocampal circuits serves as a primary pathogenic mechanism underlying the transition from the presymptomatic to the symptomatic stage of Alzheimer’s disease (AD). Finally, I will present evidence highlighting the role of the limbic thalamus in restoring synaptic and cognitive resilience to AD pathology by reinstating circuit-level homeostasis.