The calcium sensor synaptotagmin 7 is required for synaptic facilitation

Synaptotagmin 7 is shown to be essential for synaptic facilitation at a variety of central synapses, and the results pave the way for future functional studies of short-term synaptic plasticity, a fundamental form of neuronal computation. Synaptic facilitation requires synaptotagmin 7 Synaptic facilitation is a process — first observed more than 70 years ago — that allows neurons to dynamically regulate neurotransmitter release in an activity-dependent manner. It is manifest as short-term synaptic enhancement lasting for up to several hundred milliseconds. Wade Regehr and colleagues have now identified synaptotagmin 7 as the calcium sensor required for synaptic facilitation at a variety of central synapses. Previous studies had established a role for synaptotagmin 7 in the slow phase of transmission known as asynchronous release and in Ca 2+ -dependent recovery from depression. This result offers a key molecular handle for future functional studies of short-term synaptic plasticity, a fundamental form of neuronal computation. It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner 1 . At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release 2 . Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses 3 , but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release 2 , 4 , and this sensor is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed 5 , 6 . Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the presynaptic residual calcium signals are unaltered. Expression of wild-type Syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated Syt7 with a calcium-insensitive C2A domain did not. By revealing the role of Syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, a