Synaptic networks of human brain

The human brain is a biological system with remarkable complexity, energy efficiency, and computational power. It generates complex behavioral sequences, stores memories over a lifetime, and provides us with complex cognitive functions such as consciousness. Yet how cells, synapses, and circuits generate these phenomena remains unknown. One possibility is that human brain is a scaled version of the well-studied rodent brain. Alternatively, its uniqueness may emerge from the specific properties of cells, dendrites, or synapses. Distinguishing between these possibilities has been difficult, because direct information on the human brain is lacking. This is particularly striking for the hippocampus, which has been highly studied in rodents, but is largely unknown territory in humans. What are the properties of cells, synapses, and circuits in the human brain? The only way to tackle this fundamental question is to obtain direct recordings from living brain tissue extracted from human epilepsy patients. It is generally believed that such measurements are only possible in neocortical tissue, which is thought to be unaffected by the underlying disease and better preserved during surgery. However, recent work shows that hippocampal tissue is heterogeneous, including patients in which the hippocampus is highly sclerotic, but also subjects in which the hippocampus appears largely unaffected. Such non-sclerotic samples provide a unique opportunity to determine the synaptic basis of memory storage and higher- order computations in the human hippocampus. The goal of the present project is to study synapses, cells, and microcircuits in the human hippocampus. for the first time. We want to focus on the dentate gyrus, a putative pattern separation circuit, and the hippocampal CA3 region, a putative pattern completion circuit and the largest autoassociative neuronal network in the brain. In addition, we plan to examine the properties of the human mossy fiber pathway, which connects the dentate gyrus to the CA3 region. For this project, we will apply cutting-edge electrophysiology techniques to human hippocampal tissue samples, provided by the Neurosurgery Department of the Medical University of Vienna (MUW). We will focus on non-sclerotic hippocampal tissue, allowing us to approximate, as much as possible, the properties of the intact circuit. The results emerging from this project will lead to a unique data set. The expected findings will provide an answer to the long-standing question of whether the human hippocampus is a simply-scaled version of its rodent counterpart, or whether specific properties of cells, synapses, and circuits contribute to its unique performance. As such, the results will fill a major gap in the understanding of ourselves as human beings. In the long term, the results will also provide the basis for a better comprehension of human brain diseases and the development of new therapeutic strategies against these diseases.