Hindbrain synapses switch between synaptotagmin isoforms



EPFL scientists have determined that synapses in the hindbrain switch synaptotagmin isoforms as a strategy for optimizing speed and plasticity.

Synaptotagmins are calcium sensor proteins that trigger vesicle fusion in the presynaptic nerve terminal after an electrical impulse arrives. There are several isoforms in mammals, many of which are involved in calcium-driven fast neurotransmitter release. A longstanding question has been whether or not synaptotagmins function redundantly in a nerve terminal, or whether a nerve terminal, which is located at a substantial distance from the neuron’s cell body, can switch between different isoforms of the protein during its development. Publishing in Neuron, EPFL scientists have now determined that the latter is the case.

Synaptotagmin-2 (Syt2) is a closely related isoform to Syt1, and Syt2 is only found in vertebrates and there expressed mainly in hindbrain areas. Using knockout mice for both synaptotagmin isoforms, the lab of Ralf Schneggenburger at EPFL looked at synaptotagmin isoform switching in the mouse calyx of Held – a large synapse in the auditory system of all mammals.

The team found that genetic deletion of Syt2 affected transmitter release at calyx synapses only gradually during brain development. This suggested that early in development, when the nerve terminals had just formed, transmitter release is caused by another Syt isoform. Using a conditional Syt1 knockout mouse combined with viral techniques, the team could then show that Syt1 is responsible for release at this hindbrain synapse early in development, but later replaced by Syt2.

The findings demonstrate that a developing synapse in the hindbrain switches between synaptotagmin isoforms 1 and 2. Although the functional advantage for the synapses to use Syt2, as compared to Syt1 is not entirely clear, the authors suggest that Syt2 could guarantee a more fail-safe release mechanism at these relay-type hindbrain synapses.

This work was funded by the Swiss National Science Foundation and the Deutsche Forschungsgemeinschaft.


Kochubey O, Babai N, Schneggenburger R. A Synaptotagmin isoform switch during the development of an identified CNS synapse. Neuron 19 May 2016. DOI: 10.1016/j.neuron.2016.04.038