Venue: Centre Broca
Inna Slutsky
Tel Aviv University
Invited by Christophe Mulle (IINS)
Title
Plasticity-Stability Balance in Neural Circuits: From Activity Homeostasis to Alzheimer’s Disease
Abstract
Understanding how neurons and neural networks, composed of highly dynamic molecules with relatively short half-lives, maintain stable firing properties remains one of the most intriguing questions in neuroscience. Since the time of Claude Bernard, scientists have been striving to uncover the fundamental principles and molecular mechanisms that underlie homeostasis at the cellular, network, and system levels. Despite significant advances, the mechanisms that enable network-wide resilience of activity patterns remain largely unknown. In this talk, I will explore the cellular and network properties regulated by homeostatic systems, the spatial scale of this regulation, and the mechanisms behind set-point control. Furthermore, I will present evidence suggesting that activity dyshomeostasis begins during low-arousal brain states, such as anesthesia and sleep, at the presymptomatic stage in familial Alzheimer’s disease models. Finally, I will propose a model linking activity dyshomeostasis, sleep disturbances, and memory dysfunctions in Alzheimer’s disease, and present circuit-wide mechanisms that may restore this dysregulation.
Key publications
Slutsky, I. (2024). Linking activity dyshomeostasis and sleep disturbances in Alzheimer disease. Nature Reviews Neuroscience 25, 272-284. 10.1038/s41583-024-00797-y.
Shoob, S., Buchbinder, N., Shinikamin, O., Gold, O., Baeloha, H., Langberg, T., Zarhin, D., Shapira, I., Braun, G., Habib, N., and Slutsky, I. (2023). Deep brain stimulation of thalamic nucleus reuniens promotes neuronal and cognitive resilience in an Alzheimer’s disease mouse model. Nature Communications 14, 7002. 10.1038/s41467-023-42721-5.
Zarhin, D., Atsmon, R., Ruggiero, A., Baeloha, H., Shoob, S., Scharf, O., Heim, L.R., Buchbinder, N., Shinikamin, O., Shapira, I., Styr, B., Braun, G., Harel, M., Sheinin, A., Geva, N., Sela, Y., Saito, T., Saido, T., Geiger, T., Nir, Y., Ziv, Y., Slutsky, I. (2022). Disrupted neural correlates of anesthesia and sleep reveal early circuit dysfunctions in Alzheimer models. Cell Reports 38(3) 10.1016/j.celrep.2021.110268.
Styr, B, Gonen, N, Zarhin, D, Ruggiero, A, Atsmon, R, Neta Gazit, N, Braun, G, Frere, S, Vertkin, I, Shapira, I, Harel, M, Heim, L, Katsenelson, M, Rechnitz, O, Fadila, S, Derdikman, D, Rubinstein, M, Geiger, T, Ruppin, E, Slutsky, I. (2019). Mitochondrial Regulation of the Hippocampal Firing Rate Set Point and Seizure Susceptibility. Neuron, 102(5), 1009-1024.e8.
Styr, B., and Slutsky, I. (2018). Imbalance between Firing Instability and Synaptic Plastcity Drives Early-Phase Alzheimer’s Disease. Nature Neuroscience, 21(4), 463-473.