Since the early time of Descartes at the turn of the 17th 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. Individual synapses – the elementary units of information transfer – encode and store new information in response to the environmental changes through structural and functional reorganization. However, the key mechanisms that normally maintain plasticity of synapses during adulthood or initiate synapse dysfunction and loss in neurodegenerative disorders remain unknown.
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 primary mechanisms initiating synaptic and network dysfunctions in Alzheimer’s disease?
- Interplay between population firing stability of and single neuron dynamics in hippocampal networks. Collaboration with Prof. Eli Nelken (HUJI).
- Functional role of specific cell types in homeostasis of firing patterns in hippocampal circuits.
- Does hippocampus exhibit a ‘critical period’ of plasticity in response to changes in sensory experience?
- How synaptic and network plasticity is regulated by ongoing spiking patterns in the entorhinal-hippocampal circuits? Collaboration with Dr. Dori Derdikman (Technion) and Dr. Yuval Nir (TAU).
- What are the mechanisms that initiate hippocampal hyperactivity in the early stages of Alzheimer’s disease? Collaboration with Prof. Dominic Walsh (Harvard) and Prof. Joel Hirsch (TAU).
- Why do specific neuronal connections become vulnerable to degeneration in Alzheimer’s disease?
- High-resolution, single-photon imaging of synaptic vesicle recycling and calcium dynamics at the level of single synapses;
- Two-photon microscopy combined with fluorescence lifetime imaging microscopy (2pFLIM)
- Electrophysiology: intracellular patch-clamp recordings in brain slices and cultures, MEA (multiple-electrode-array) recordings in neuronal cultures, in vivo extracellular recordings;
- FRET spectroscopy: real-time imaging of inter-molecular interactions at nano-scale in live neurons;
- In vivo gene delivery using lentivirus and adenoassociated virus vectors;
- Genetic tools: target-specific expressing genetically-encoded fluorophore-fused proteins of interest, site-directed mutagenesis, protein knockdown;
- Biochemistry: ELISA, Western blotting, immunoprecipitation, immunocytochemistry.