Synaptic connections underlie learning and memory in the brain and are dynamically formed and eliminated during development and in response to stimuli. Quantifying changes in overall density and strength of synapses is an important pre-requisite for studying connectivity and plasticity in these cases or in diseased conditions. Unfortunately, most techniques to detect such changes are either low-throughput (e.g. electrophysiology), prone to error and difficult to automate (e.g. standard electron microscopy) or too coarse (e.g. magnetic resonance imaging) to provide accurate and large-scale measurements.