The first synapse

In the late 1970s, two separate groups attempted to document synapses in gut endocrine cells using conventional electron microscopy. Unfortunately, both failed. One reported a micrograph in which the closest nerve is within 100 nm of a putative enteroendocrine cell; and the second claimed to have identified a synapse, but the image resolution was poor and structures are indistinguishable, so it has been largely ignored.

At the time, they were limited by inadequate technology. Transgenic mice did not exist and serial-sectioning EM demanded serious manual labor. Today, transgenic mice allow us to identify enteroendocrine cells by means of fluorescence. Manual serial-section EM is being replaced by fully automated 3D electron microscopy or serial block face scanning electron microscope (SBEM). And, one third of the US population is obese. Obesity has enlarged the need to understand the signals that trigger satiety; in particular, those at the gut level where food is sensed by enteroendocrine cells.

We are using volumetric electron microscopy techniques to uncover the ultrastructural features the points of contacts between enteroendocrine cells and nerves. This connection is the first node between nutrient sensing and electrochemical transduction that modulates brain function and behavior.