Watching Minis Sparkle in the Neurobiology Course | @HaniehFalahati

Watching Minis Sparkle in the Neurobiology Course | @HaniehFalahati
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Minis? Sparse twinkles? Below, MBL Neurobiology course faculty member Michael Hoppa explains what is happening in this sparkling video.

By Michael Hoppa, Dartmouth College
Faculty, MBL Neurobiology course 2018

This movie was obtained by students in my research group for the Cell Biology section of the MBL Neurobiology course. We set out to investigate synaptic transmission (communication between nerve cells) in the context of a rare neurological defect associated with diabetes that we believe alters synaptic transmission in the brain.

Synapses are specialized sites for fast information transfer: Packets of neurotransmitter can be released less than 1 millisecond after the arrival of an electrical impulse known as an action potential. In addition to this action potential-induced release of neurotransmitter, synapses also release small packets of neurotransmitter spontaneously, a phenomenon that has been dubbed a “Mini” due to its small amplitude when recorded using electrophysiology.

Despite the fact that Minis were identified in the 1950s (by Sir Bernard Katz in frog neuromuscular junctions), their role in neurological function is unclear. However, over the past decade, evidence has built up that Minis could have specialized physiological roles in the development and function of the neuronal circuit.

Unfortunately, it is very hard to study this process in elaborate mammalian neurons due to the small and spontaneous (or stochastic) nature of Minis. We had reason to believe that this type of spontaneous transmission is disturbed in some patients with neonatal diabetes, so we hoped to develop new methods at MBL to optically record spontaneous neurotransmission to further our studies back in my laboratory at Dartmouth College.

I was very excited to read about a new fluorescent reporter developed by Loren Looger’s group at Janelia Farms called iGluSnFr (“Glu Sniffer”) that could potentially be adapted to our microscope system to measure Minis optically. Working with a talented group of students in the Neurobiology course — Hanieh Falahati (Yale), Jose Miguel Andrade-Lopez (Stanford) and Raul Ramos (Brandeis) — as well as a post-doc from my Dartmouth lab, In Ha Cho, we were able to record many Minis (the tiny sparkles in the video) and compare them to traditional evoked release when the neuron fired an action potential (the large flash).

The students worked together to capture this movie (and many more!) Each tiny swelling is a synaptic terminal (we have over a trillion of these between our ears). We obtained some great preliminary data about what controls the magnitude of Minis and Hanieh developed a computer program to analyze this data very efficiently. This is, to my knowledge, is the first time that both spatial and temporal information about Minis can be obtained from a neuron. It opens up many important research questions that we are excited to pursue back at Dartmouth and hopefully next summer at the MBL!

Credit and thanks to Olympus Life Science, Hamamatsu Photonics, and the Looger Lab at HHMI Janelia Research Campus for enabling technologies for this experiment.