Regulating Hippocampal Plasticity- From Dynamics of Single Synapses to Alzheimer’s Disease

Our research focuses on two key questions:
How do individual neurons and neural networks achieve an ongoing balance between stability and plasticity under a constantly changing environment?
What are the mechanisms driving synaptic and network dysfunctions in Alzheimer’s disease?

Projects in the lab:

• Interplay between population firing stability and single neuron dynamics in the hippocampus of behaving mice.
• Functional role of firing rate homeostasis  in hippocampal circuits of behaving mice.
• Regulation and mysregulation of activity set points by sleep in hippocamapl circuits.
• Do circuits with different functions display distinct homeostatic principles?
• What are the building blocks of the core homeostatic machinery underlying stability of central circuits?
• Do failures in firing homeostasis drive Alzheimer’s disease pathophysiology?
• What is the role of sleep-wake states in dysregulation of activity set points in Alzheimer’s disease?
• Re-adjustment of dysregulated activity set points as a new approach to treat brain disorders associated with aberrant network activity.

Scientific tools:

• Calcium imaging from large-scale populations of hippocampal neurons in behaving mice using miniaturized fluorescence microscope;
• Electrophysiology: intracellular patch-clamp recordings in brain slices and cultures, MEA (multiple-electrode-array) recordings in neuronal cultures, in vivo extracellular recordings;
• Targeted manipulations of neuronal activity using chemogenetic and optogenetic tools;
• High-resolution, quantitative imaging of synaptic vesicle recycling, calcium dynamics and mitochondrial functions;
• Two-photon microscopy combined with fluorescence lifetime imaging microscopy (2pFLIM);
• In vivo gene delivery using lentivirus and adenoassociated virus vectors;
• FRET: real-time imaging of inter-molecular interactions at nano-scale in live neurons;
• Molecular tools: target-specific expressing genetically-encoded fluorophore-fused proteins of interest, site-directed mutagenesis, protein knockdown.

For more information:

Prof. Inna Slutsky
Head, Department of Physiology and Pharmacology
School of Medicine, room 511
Tel Aviv University, Tel Aviv 69978, Israel
Tel: +972-3-640 6021 (Office)
Tel: +972-3-640 6074 (Lab)
Fax: +972-3-640 9113
Email: islutsky@tauex.tau.ac.il
Web: https://www.slutskylab.com/