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Chunk #1 — Introduction

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Microfluidic local perfusion chambers for the visualization and manipulation of synapses.
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Local changes at synapses are critical for plasticity, yet there are limited techniques to investigate local processing within synaptic regions. One technique, glutamate uncaging, which uses photoconversion to yield active glutamate, has revealed much about local processing following neurotransmitter release and has been an important advance for studying mechanisms of synaptic plasticity (Harvey et al., 2008; Lee et al., 2009). Drawbacks of this technique include the limited set of available caged compounds as well as the bath application of the caged molecule to the entire culture/tissue. The recent development of optogenetics to selectively activate or inactivate regions of synapses has also shown great promise (Zhang et al., 2007). These methods require genetically modified neurons to express light-sensitive ion channels. There have also been studies which use small perfusion pipettes to alter local environments at sites of synaptic contact (Song et al., 1997; Sutton et al., 2006; Sutton et al., 2007). While local perfusion allows for the application of any drug or compound, it is cumbersome to set-up and implement, treats a single dendrite or process at a time, and has a relatively slow on-off time for manipulations.