Neuronal Plasticity, Learning, and Memory
Who we are as human individuals is determined to a large degree by the sum-total of our memories, be they intimate recollections, precious facts, useful skills or convenient habits. Furthermore, we now know that the brain systems that permit us to mentally reenact selected moments of our personal past also enables us to embark on a private mental time travel to the future, plan, simulate scenarios and fly on the wings of our imagination. How does the brain accomplish all that? And why is it that sometimes our memory tricks us to confound the real with the imaginary, and that sometimes it may even fail us completely? Why is it, for example, that sometimes we are quick to abandon veridical recollections for erroneous information shared with us by others? And can we enhance memory on the one hand, and prevent or ameliorate memory deficits on the other?
These and related questions concerning memory are the focus of research of several research group in our Department. Together, we tackle memory at multiple levels of analyses, ranging from the basic neuronal machinery that implements synaptic and neuronal plasticity - i.e. elementary building blocks of systems that encode and store memory - to the concerted activity of neuronal circuits that encode and maintain experience-dependent mental representations of the world, to the brain systems that store mental images of events in our life and of places that we visited, and those that control the expression of these recollections at any given point in time. Some of us also investigate the processes and mechanisms that shape the memory of individuals in social milieu. Our multidisciplinary, multi-level experimental approach to neuronal plasticity, learning and memory encompasses a spectrum of cutting-edge methods, ranging from state-of-the-art molecular biology and electrophysiology in animal models to sophisticated psychophysics and behavior, modeling, and the most advanced behavioral protocols and functional neuroimaging of the behaving human brain.
Stress, Emotions and Neuropsychiatry
The biological response to stress is concerned with the maintenance of homeostasis in the presence of real or perceived challenges. This process requires numerous adaptive responses involving changes in the central nervous, neuroendocrine and immune systems. When a situation is perceived as stressful, the brain activates many neuronal circuits linking centers involved in sensory, motor, autonomic, neuroendocrine, cognitive, and emotional functions in order to adapt to the demand. However, the details of the genes and pathways by which the brain translates stressful stimuli into the final, integrated biological response are presently incompletely understood. Nevertheless, it is clear that dysregulation of these physiological responses to stress can have severe psychological and physiological consequences, and there is much evidence to suggest that inappropriate regulation, disproportionate intensity, or chronic and/or irreversible activation of the stress response is linked to the etiology and pathophysiology of anxiety disorders, depression and other psychopathologies.
The research groups at the Department of Brain Sciences are studying the neurobiology of stress and emotions by focusing on the specific genes and brain circuits, which are associated with, or altered by, behavioral or physiological challenges. Recent and emerging findings from our research groups listed below, provided important insights into the brain mechanisms by which homeostatic challenges affects psychological and physiological disorders.
We make decisions almost every moment of our life, some are small and less significant, and some are major and have crucial influence on the course of our lives. Decisions rely on information gathered previously (memory), which is weighted with the current flow of information (sensory perception), consideration of the possible alternatives, and reasoning to reach a final decision – usually resulting in an action or lack thereof. Furthermore, decisions may be driven by external cues but also depend on internal volitional and stochastic processes. The groups studying decision making in the department use several techniques to shed light on the different mental processes involved in this decision making. We rely on psychophysical studies to unveil perceptual mechanisms in humans, behavioral and functional imaging studies of the human brain during memory formation and active decisions, and electrophysiological studies in animals as well as diagnostic intra-cranial recordings in patients -- to unveil the neuronal networks involved in these processes. We combine expertise from different fields, such as behavioral paradigms from cognitive psychology, electrophysiology in behaving animals and functional imaging in humans, computational approaches and modeling, and believe that only a multidisciplinary integrative approach can help decipher the complex process of decision making.
The neuron is the basic element of brain function. However, neurons do not act singly – rather, they act through complex yet coherent neural circuits and networks, in order to generate sensory perceptions, behaviors, memories and thoughts. Although the behavioral output of different neural circuits are highly diverse, the principles of their structure and function is often surprisingly similar across different brain regions and animal species. This suggests that understanding the common fundamental building blocks of neural circuits will allow us to decipher the function of the brain as a whole. Such elucidation requires a multi-level approach and benefits greatly from cooperation between experimentalists and theorists.
Understanding the design and function of neural circuits requires the combination of diverse approaches. Integrating researchers from a variety of backgrounds such as biology, physics, mathematics, computer science, engineering, and psychology, we develop and apply novel approaches to study neural circuits. We combine extracellular and intracellular neural recording, imaging techniques spanning all scales from sub-cellular calcium imaging to whole-brain functional magnetic resonance imaging, and state-of-the-art anatomical, molecular and genomic techniques. These experimental approaches are complemented by theoretical studies of microcircuits and large-scale neuronal ensembles. The questions that are currently being addressed range from studies of active-sensing systems, through the neural codes of learning and memory, neural circuit plasticity and the neural basis of individual and group behaviors.
Theoretical and Computational Neuroscience
The brain is acting through the interaction of billions of neurons and myriads of action potentials that are criss-crossing within and between brain areas. To make sense of this complexity, one must use mathematical tools and sophisticated analysis methods in order to extract the important information and create reduced models of brain function. Together, faculty members and students at the Weizmann Institute, coming from diverse quantitative backgrounds such as physics, engineering, mathematics and computer science, are breaking new cutting-edge avenues in computational and theoretical neuroscience. We are using mathematical tools taken from Statistical Physics, Dynamicsl Systems, Machine Learning and Information Theory -- to name just a few -- in order to create new models and theories of brain function. Both analytical approaches and simulations are used heavily. By intense collaborations with experimental laboratories, these new theories and computational tools are put to the test, and then refined further. Our aim is to unravel the basic principles of brain operation and the underlying neural codes.