Specificity of Synapse Formation

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Cognition in the human brain depends upon extraordinarily precise connections between brain cells (neurons). If neural pathways do not form correctly or become damaged, then impairments of brain function will inevitably result. Although a great deal is known about molecules that comprise connections between brain cells (synapses) there is only a rudimentary understanding of the molecular markers that direct any particular neuron to its correct target destination. The goal of this project is employ electrophysiological, molecular, and immunocytochemical approaches to identify molecules that specify selective synaptic connectivity between brain cells. The brain area to be studied is the hippocampus, a structure known to be important for learning and memory in all mammals, including humans. The hippocampus is highly organized, with clear patterns of connectivity between distinct cell populations. The initial focus will be to build upon preliminary data which indicate that potential "signpost" molecules show cell-type specific distribution patterns. Subsequent experiments will manipulate these molecules to test directly their role in directing synapse formation between specific populations of cells. Student participation will be encouraged throughout all aspects of this work and results will be disseminated at public meetings and via scientific publications. The significance and impact of these studies is clear. In order to fully understand how brains form in embryos and young organisms throughout the animal kingdom, fundamental knowledge must be obtained about how individual cells are able to seek out and form synapses with their correct targets. The work described here will make an important contribution to achieving that goal.