Investigating Thalamocortical Spike Dynamics to Increase Sleep Stability and Memory in Alzheimer’s Disease

Our long-term objective is to determine how thalamic networks contribute to sleep and memory in the normal and diseased brain. The goal of this project is to investigate the basic mechanisms by which the spike dynamics in cognitive thalamic circuits contribute to sleep stability and memory consolidation. A growing body of literature indicates that sleep fragmentation occurs in pre-clinical stages and predicts the progression of Alzheimer’s Disease (AD). Thalamocortical neurons have been implicated in the progression of AD and their sleep activity is also associated with increased sleep stability. Remarkably, the mechanistic link between thalamic spike activity, sleep stability, and AD progression remains unclear. We aim to answer two questions. First, we will use optogenetics, pharmacology, and electrophysiology in behaving rats to understand how the spike dynamics (such as spikes occurring in groups or bursts) in thalamocortical neurons regulate sleep microarchitecture and stability. Second, we will use a rat AD model to test the hypothesis that increasing the occurrence of spike bursts in thalamocortical neurons delays the progression of AD disease and the deterioration of memory. The outcome of this work will be a better understanding of the basic mechanisms and causal contribution of thalamocortical neurons to sleep stability. We will also determine how increasing sleep stability benefits memory function and delays AD progression in a rat model of AD. Given the common occurrence of sleep disruption in neurodegenerative diseases, these outcomes can significantly contribute to the development of effective therapeutic interventions for Alzheimer’s Disease and related dementias. Project Number: 1R03AG093243-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Carmen Varela | Institution: FLORIDA STATE UNIVERSITY, TALLAHASSEE, FL | Award Amount: $296,232 | Activity Code: R03 | Study Section: Behavioral Neuroendocrinology, Neuroimmunology, Rhythms, and Sleep Study Section [BNRS] View on NIH RePORTER: https://reporter.nih.gov/project-details/11119069