What happens when synapses run out of transmitter?
The recent Nobel Prize Award in Medicine highlights the importance of vesicle-based transport for different kinds of cells. One of the recipients, Thomas Sudhof, has contributed extensively to our current understanding of vesicle function in the synapses of neurons. Despite the fact that this is one of the most studied areas in neuroscience, we don’t have a satisfactory theory that explains why information, ostensibly represented in high-fidelity using precisely timed spike trains, is then transferred with a low-fidelity, probabilistic mechanism that uses soft sacks of chemicals. A paper recently published in the journal Neuron, takes a closer look at this process in inhibitory neurons of the hippocampus. The authors find that if neurons continue to spike beyond a certain rate for a long enough time, their vesicles may still retain their potential for to fuse at release sites, but the synapse eventually runs out of transmitter to fill them with. Furthermore, they show that if the synapse can not supply sufficient transmitter, either through transport from the soma, or through local metabolic processing and uptake, then the synapse adapts by reducing the number of cycling vesicles.