Prof. Inna Slutsky

Chair, Department of Physiology & Pharmacology, Sackler Faculty of Medicine

Editorial Board Member: eLife, Scientific Reports, Frontiers in Cellular and Molecular Neuroscience;

Ad hoc Reviewer:  Neuron, Nature Neuroscience, Nature Communications, eLife, EMBO Journal, PLOS Biology, Acta Neuropathologica, Journal of Neuroscience, Journal of Neurophysiology, Neuroscientist, Journal of Alzheimer’s Disease, Neurobiology of Aging, Trends in Neuroscience.

Member of American Federation for Aging Research (AFAR) National Scientific Advisory Council;

Scientific Advisory Board, CIBB, Neuroscience and Disease area, Coimbra University, Portugal.

Member of Balvatnik Awards for Young Scientists Committee, New York Academy of Science;

Member of grant commitees – ISF, BSF, AFAR.

Member of Clore committee for PhD fellowships;

2016-2020 Member of Azrieli commite for Phd fellowships;

2012-2020 Member of Ph.D. Program committee, Sagol School of Neuroscience, Tel Aviv University;

1992 - 1995  BSc in Biology, Hebrew University, Israel

1996 - 2002  PhD in Neurobiology, Hebrew University, Israel

2002 - 2005 PostDoc in MIT, Picower Institute for Learning and Memory

Interplay between Stability and Plasticity in Hippocampal Circuits

Since the early time of Descartes at the turn of the 17^th century, scientists and philosophers have been searching for the physical correlate of thoughts and memories. During the past 60 years, mounting evidence indicates that experience-dependent changes in synaptic transmission and neuronal wiring, phenomena collectively termed synaptic plasticity, underlie the cellular basis of neural computation, learning and memory. Hebbian-like plasticity is crucial for refinement of neural circuits and information storage, however, alone it is unlikely to account for the stable functioning of neural networks. Both, stability and plasticity are hallmarks of brain function that enable adaptations to unpredictable and dynamic environment, experience and learning. Coping with constantly changing environments, neural circuits need to spend a considerable amount of their available energy to maintain homeostasis and to minimize the effects of stochastic events. Destabilization of hippocampal and cortical circuits has been widely documented in neurodegenerative disorders, e.g. Alzheimer’s disease, the most frequent form of late-life dementia. However, the key mechanisms that underlie stability of activity patterns in central mammalian neural circuits are largely unknown. Furthermore, how disruption of these mechanisms affects the progression of Alzheimer’s disease remains an enigma.

Our research focuses on two key questions:

1. How do individual neurons and neural networks achieve an ongoing balance between stability and plasticity under a constantly changing environment?
2. What are the mechanisms driving synaptic and network dysfunctions in Alzheimer’s disease?

Selected publications:

Ruggiero, A*, Katsenelson, M*, Slutsky, I. (2021). Mitochondria: new players in homeostatic regulation of firing rate set points. TINS (In press).

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.

Rice HC, de Malmazet D, Schreurs A, Frere S, Van Molle I, Volkov AN, Creemers E, Vertkin I, Nys J, Ranaivoson FM, Comoletti D, Savas JN, Remaut H, Balschun D, Wierda KD, Slutsky I, Farrow K, De Strooper B, de Wit J (2019) Secreted amyloid-β precursor protein functions as a GABA_BR1a ligand to modulate synaptic transmission. Science 363:eaao4827.

Frere, S., and Slutsky, I. (2018). Alzheimer’s Disease: From Firing Instability to Homeostasis Network Collapse. Neuron 97, 32-58.

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.

Gazit, N., Vertkin, I., Shapira, I., Helm, M., Slomowitz, E., Sheiba, M., Mor, Y., Rizzoli, S., and Slutsky, I. (2016) IGF-1 Receptor Differentially Regulates Spontaneous and Evoked Transmission via Mitochondria at Hippocampal Synapses, Neuron 89, 583-597.

Slomowitz, E., Styr, B., Vertkin, I., Milshtein-Parush, H., Nelken, I., Slutsky, M., Slutsky, I. (2015). Interplay between population firing stability and single neuron dynamics in hippocampal networks. Elife 4.

Dolev, I., Fogel, H., Milshtein, H., Berdichevsky, Y., Lipstein, N., Brose, N., Gazit, N., Slutsky, I. (2013). Spike bursts increase amyloid-beta 40/42 ratio by inducing a presenilin-1 conformational change. Nature Neuroscience, 16: 587-595.

Laviv T, Riven I, Dolev I, Vertkin I, Balana B, Slesinger PA, and Slutsky I. (2010). Basal GABA regulates GABA(B)R conformation and release probability at single hippocampal synapses. Neuron 67, 253-267.

Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, and Slutsky I. (2009). Amyloid-[beta] as a positive endogenous regulator of release probability at hippocampal synapses. Nature Neuroscience 12, 1567-1576.

Slutsky, I., Abumaria, N., Wu, L.J., Huang, C., Li, B., Zhao, X., Govindarajan, A., Zhao, M.G., Zhuo, M., Tonegawa, S., Liu, G. (2010). Increasing Synaptic Density and Enhancing Memory by Brain Magnesium. Neuron, 65: 165-177.