Mechanisms underlying short-term synaptic plasticity and synapse formation between identified neurons

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All nervous system functions in animals, ranging from simple reflexes to complex motor patterns and learning and memory rely upon synaptic connectivity between networks of brain cells – termed neurons. Neurons communicate with each other through highly specialized structures called synapses, and it is this precise orchestration of synaptic connectivity during early development that forms the basis for all brain functions after birth. Understanding how synapse-specificity is achieved in the first instance, and how neuronal communications are established and modulated throughout life, is therefore central to our understanding of all brain function. However, due primarily to the complexity of the vertebrate brain (tens of billions of cells and even larger numbers of glia), direct and simultaneous recordings between select groups of pre-and postsynaptic neurons are often difficult to achieve reliably. As such, our knowledge regarding fundamental inter-workings of the mammalian brain cells remain largely unknown. In our lab, we have thus opted to develop an invertebrate model, where we have defined mechanisms of synapse formation and synaptic plasticity at a resolution that is unattainable elsewhere. We have exploited this model to define fundamental mechanisms of synaptic connectivity, and have demonstrated how trophic factors activate a human tumor suppressor MEN1 gene through activity dependent mechanisms, which in turn control the expression of nicotinic acetylcholine receptors in the postsynaptic neurons. We now wish to decipher cellular and molecular mechanisms underlying MEN1 function in this model system. Using modern molecular and biomedical engineering techniques, our lab was the first in the world to develop a true bionic hybrid (neuronal stimulation and recordings achieved through the chip). These novel brain-chip recording technologies have significantly enhanced our ability to interrogate multiple neurons concurrently and over an extended time period. An exposure to these state of the art electrophysiological techniques has also helped us train the future generation of highly qualified individual in the interdisciplinary field of biomedical engineering. Our short-term goals now are to use these techniques to first decipher mechanisms of synaptic connectivity, whereas in the longer-term, we wish to develop these technologies further to enable brain-controlled prosthetic devices for human applications. We believe that our biomedical engineering approach to brain research will not only create new knowledge but also help create “made in Canada” technology, which will contribute significantly to our economy.