FMI scientists discover brain structures associated with learning

Scientists at the Friedrich Miescher Institute for Biomedical Research (FMI, part of the Novartis Research Foundation) have discovered neuronal connections which are formed in the brain when learning occurs, and which ensure the precision of memory. This work represents an important step on the path towards an improved understanding of how learning and memories are stored in the brain. The findings were published today in the online edition of Nature. How are experiences and learning stored in the brain? This “simple” question has intrigued scientists for several generations. Since the visionary neuroscientist and Nobel laureate Santiago Ramón y Cajal first postulated (at the end of the nineteenth

century) that structures in the brain change during learning, and that what is learned – or the memory of what has been learned – is represented in neuronal connections, researchers have sought to detect structural changes of this kind. They have been searching, as it were, for nerve cells which encode the Pythagorean theorem or the memory of a red dress. So far, their efforts have not been successful, as the sheer number of neuronal connections, or synapses, in the brain has proved an insuperable obstacle. Neurobiologists at the FMI have now demonstrated a direct link between the formation of new synapses in the brain and a learning process, plus the quality of the associated memory. These findings were reported today in the online edition of Nature. A team led by the group leader Pico Caroni, who is also a professor at the University of Basel, studied neurons in the hippocampus of mice learning to navigate a water maze. The hippocampus is a region of the brain which is essential for learning and recall. During learning, the number of synapses onto interneurons was found to double along hippocampal mossy fibers. These new synapses indirectly inhibited other cells, known as pyramidal neurons, thereby contributing to the precision of what was learned. They thus laid down, for example, that at a certain point in the maze, the mouse should go to the right, but not to the left, straight ahead, back, up, or down. When the formation of these synapses was inhibited by the administration of a drug, the mouse would still find its way, but with less precision – it did

not take the shortest route to the goal. Caroni explains: “Our experiments have, for the first time, demonstrated a clear association between the formation of new synapses and behavior after learning. So we’ve shown a specific structural change in the brain induced by learning – and also that this change is required for the precision of learning.” The researchers also found that the newly formed synapses often disappeared again several days after the end of the learning process. However, even weeks later, this did not prevent the mice from navigating the maze successfully, although precision was diminished. “What we’ve discovered,” says Caroni, “are not structures which are indicative of memories, but structures which are necessary for precise recall of what’s been learned. If these mechanisms are disrupted, behavior can be diverted by more dominant stimuli, which could play an important role in many memory disorders.”  Prof. Pico Caroni; Pico Caroni is a group leader at the FMI and Professor of Neurobiology at the University of Basel. He is interested in the mechanisms that control the formation, the maintenance and the turnover of

synaptic connections in the brain, namely in the hippocampus. He has been a pioneer in understanding how these processes relate to learning, adaptation and memory and how they are impaired in disease. –  Plasticity of neuronal connections; We investigate regulatory mechanisms that control the formation, maintenance and turnover of synaptic connections (structural plasticity), and how this plasticity relates to learning and behavior. We are particularly interested in mechanisms determining the plasticity of defined neuronal circuits, as they may inform us about principles of learning, adaptation, and resilience to disease in the nervous system. Applying this approach to the hippocampus, a brain structure with a critical role in learning and memory, we investigate how learning and experience specifically influence circuit structure, and how that structure in turn impacts on behavior. We are taking a comprehensive approach to hippocampal and cerebellar circuits, with studies ranging from the specification and assembly of defined microcircuits during development, to the roles of these microcircuits in adult plasticity. In a second line of research, we investigate mechanisms of disease in neurodegeneration, focusing on mouse models of motoneuron disease. As well as mouse genetics, mouse behavior, neuroanatomy, single cell genomics and live imaging, we use transgenic mice expressing fluorescent chimeric proteins in single neurons to visualize neurons and subcellular components in situ. News from: FMI – Friedrich Miescher Institute for Biomedical Research

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