Summary: Synaptotagmin 2 is the major calcium sensor in GABAergic synapses, a new study reports.

Source: IST Austria.

Calcium sensor at inhibitory synapse identified.

Synapses, the connections between neurons, are different, depending on the chemical they use as transmitter. Signal transmitters, or neurotransmitters, are released at the synapse after calcium ions flow into the neuron. The type of synapses that use a signal transmitter called GABA – the GABAergic synapses — stand out because of their speed and precision. But the secret behind their speed was not fully known until now, and neither was the sensor they use to detect the inflowing calcium.

Both questions were solved in a study published today in Cell Reports by Peter Jonas, Professor at the Institute of Science and Technology Austria (IST Austria), together with his group and researchers at the Max Planck Florida Institute for Neuroscience. They found that GABAergic synapses achieve their remarkable signalling speed and reliability partly because of the sensor they use to measure the amount of calcium in the neuron, and that synaptotagmin 2 is the major calcium sensor in this kind of synapses.

“We have, for the first time, identified the calcium sensor that triggers neurotransmitter release at an inhibitory synapse”, summarizes Peter Jonas.

Interneurons that use GABA as neurotransmitter play a key role in controlling activity in neuronal microcircuits. In all brain regions and species, the hallmark of these GABAergic interneurons is their signalling speed: the delay between stimulation and response lies in the submillisecond range.

Peter Jonas and his team asked whether the calcium sensor that triggers neurotransmitter release contributes to this speed. In their study, they investigate the synapse between basket cells and Purkinje cells. This major inhibitory synapse is located in the cerebellum, a brain region that plays an important role in motor control.

While synaptotagmin 1 is the calcium sensor used at excitatory synapses, Peter Jonas and colleagues identify synaptotagmin 2 as the major calcium sensor in inhibitory GABAergic interneurons in the cerebellum. They demonstrate that synaptotagmin 2 triggers a quicker release of neurotransmitter than synaptotagmin 1. At the same time, synaptotagmin 2 also causes a faster refilling of vesicles with neurotransmitter, so that the neuron is ready to send another signal more quickly. This has important consequences for the function of GABAergic interneurons, explains Peter Jonas: “Using synaptotagmin 2 is one reason why GABAergic synapses send signals so fast. Synaptotagmin 2 may control the speed of inhibition in microcircuits, and allow GABAergic synapses to maintain their output by quickly replenishing the pool of neurotransmitter.”

Funding: The study was funded by the Austrian Science Fund, European Research Council.

Source: Elisabeth Guggenberger – IST Austria
Image Source: NeuroscienceNews.com image is credited to IST Austria.
Original Research: Full open access research for “Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse” by Chong Chen, Itaru Arai, Rachel Satterfield, Samuel M. Young Jr., and Peter Jonas in Cell Reports. Published online January 17 2016 doi:10.1016/j.celrep.2016.12.067

Abstract

Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse

Highlights
•Syt2 is the Ca2+ sensor of fast transmitter release at a cerebellar GABAergic synapse
•Syt2 triggers transmitter release with faster time course than Syt1
•Syt2 ensures faster replenishment of the readily releasable pool than Syt1
•Syt2 is essential for fast feedforward inhibition in cerebellar microcircuits

Summary
GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca2+ sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ∼10%, identifying Syt2 as the major Ca2+ sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits.

“Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse” by Chong Chen, Itaru Arai, Rachel Satterfield, Samuel M. Young Jr., and Peter Jonas in Cell Reports. Published online January 17 2016 doi:10.1016/j.celrep.2016.12.067