Molecular & Functional Neurobiology of Learning & Memory
The human brain is probably the most complex creation of our universe within the limits known to the human civilization. It is astonishing that hundreds of millions of years of evolution led to such a convoluted structure, as mammals’ brain, particularly, the human brain from so the most primitive reticular neural system found in Cnidaria, such as jellyfish. Our neural system is all we are, our personality, our behavior, our feelings and emotions, our thoughts and ideas, even the universe surrounding us exists as it is perceived and interpreted by our brain. No doubt, it is of paramount importance for the humanity to understand how this fascinating system operates, how it creates the world we are living in. These and other enormous amount of questions always tackled the human mind from the sophists of the antique ages towards the nowadays scientists. Although everything related to the brain excites curiosity, however process underlying memory formation and its deterioration is the major interest of our laboratory research.
The research interest of our laboratory mainly focuses on understand molecular and functional mechanisms underlying memory encoding and formation. Molecular and functional study of memory is assumed to allow identification of weaknesses in the mechanism of memory formation and encoding. In turn, deteriorations in these weak points of the mechanisms may serve as trigger for development of cognitive impairments and neurodegenerative diseases.
The current thinking about memory mechanisms focus on two approaches: one approach emphasizes the role of hallmark molecules linked to the functional and morphological changes upon memory formation; the second approach focus on enhancement of interaction between specific neurons within the neural networks (NNs) storing the memory traces. The first approach relates to the well-studied classical molecular and cellular neuroscience, the main dogma of which states that long-term synaptic plasticity is the cellular correlate of memory formation and retention, while the second approach states the logic of NN as a base of memory formation. Our research interest encompassed both of the approaches and extending them by introduction of new concepts of understanding of memory mechanisms.
Major Directions of Research
Concerning the classical molecular and cellular neuroscience approach, we follow the molecular and functional study of memory. In this approach, we promote the concept of dynamic protein-protein interaction network domains assembled around the key regulator proteins, which predetermine the fate of molecular mechanisms of memory formation and their disorders. We consider that factors leading to memory impairment, e.g. aging, should affect the signaling interaction networks of these key molecules. Our endeavor to identify these dynamic signaling networks and associated key regulator proteins led us to several important network domains responsible in memory formation at its different stages. Currently, we are investigating the role of these domains and their key regulator proteins, which include different protein kinases and synaptic proteins. We expect the further outcome of our research will create a robust systemic platform of the key regulator-based framework, which will serve as a reference for the study of disorders involving memory deterioration. Hence, using our platform, we intend to study the role of the key regulators in pathogenesis of memory impairment and as possible therapeutic targets. Concepts of the key regulators demonstrated its robustness in the study of potential shared mechanisms of pathogenesis of early cognitive impairments and depressive-like behavior. This study is in progress and conducted in close collaboration with Prof. A. Pinhasov’s laboratory. Based on the research, we approached to the important field of investigation of alteration in molecular and functional mechanisms of memory formation upon normal and diseased aging processes.
In regard of the second approach, which implicates artificial NNs for understanding information processing and encoding in the neural system, we introduce fundamentally a new concept, which ditch the classical simplified model of the neurons and the principal processing units. Instead, we hypothesize a non-deterministic, quantum-like behavior of the neural system with subsequent implications on the information processing and encoding. This novel concept is so far on the stage of theoretical modeling. Methodologies necessary for experimental implementation of the concept is not available yet, although the technology exists. Hence, currently, we are working to design and assemble the concept device, which would be capable to conduct experimental test of the proposed idea.
In addition to the fundamental research, our laboratory is interested in the applicative and clinical aspects of neuroscience. Our laboratory is investigating the role of non-ionizing electromagnetic radiation on protein misfolding as a part of potential ways to affect protein aggregation issues occurring in neurodegenerative diseases, such Alzheimer’s disease, Huntington disease, prion disease etc.
Major Questions Asked
Overall, research conducted in our laboratory is tightly focused on memory mechanisms and its impairment; however, we use very distinctive theoretical and experimental approaches relying on wide interdisciplinary research. To achieve our goals we ask numerous fundamental questions:
Which protein-protein interaction network domains and key regulators of the networks orchestrate signal transduction processes from synapses to the gene expression/ protein translation back to the synapses?
Which de novo synthesized proteins are the core of memory engram?
What is the dynamic of assembly and disassembly of signaling networks to affect memory formation?
What is the relation between memory formation key regulators and molecular mechanisms of aging related cognitive impairment and neurodegeneration?
Which shared molecular events, protein-protein interaction networks and key regulator proteins are involved in common mechanisms of aging related cognitive impairment and depression?
How does probabilistic behavior of the electrical activity in the neural system lead to deterministic information processing?
What is the minimal information unit processed by the neural system, if any?
What is the quantum basis of information processing in the brain?
More detailed description of our projects is presented in the Research section.
Head, the Molecular & Functional Neurobiology group
Chairman, the Integrative Brain Science Center - Ariel (IBSCA)
Department of Molecular Biology
Faculty of Natural Sciences
Phone (office): +972-3-9143068
Fax (office): +972-3-9143068
Phone (Lab): +972-3-9143069
Skype (work): izhak.michaelevski