The calcium-sensing protein synaptotagmin 7 mediates facilitation that is masked by depression, but supports frequency-invariant transmission in mouse cerebellar and vestibular synapses. In most parts of the brain, synaptic strength varies as a function of neuronal firing frequency, a phenomenon known as 'short-term synaptic plasticity'. This fundamental nonlinearity in synaptic transmission has to be compensated for to achieve frequency-independent transmission in some auditory, vestibular and cerebellar circuits. Now Wade Regehr and colleagues show that synaptotagmin 7, a calcium-sensing protein, supports a short-term facilitation that increases with firing frequency and thus compensates for use-dependent depression at synapses in the cerebellum and in the vestibular system. The resulting constant synaptic strength over a wide range of firing frequencies allows for efficient encoding of neuronal firing rates. At most synapses in the brain, short-term plasticity dynamically modulates synaptic strength. Rapid frequency-dependent changes in synaptic strength have key roles in sensory adaptation, gain control and many other neural computations1,2. However, some auditory, vestibular and cerebellar synapses maintain constant strength over a wide range of firing frequencies3,4,5, and as a result efficiently encode firing rates. Despite its apparent simplicity, frequency-invariant transmission is difficult to achieve because of inherent synaptic nonlinearities6. Here we study frequency-invariant transmission at synapses from Purkinje cells to deep cerebellar nuclei and at vestibular synapses in mice. Prolonged activation of these synapses leads to initial depression, which is followed by steady-state responses that are frequency invariant for their physiological activity range. We find that synaptotagmin 7 (Syt7), a calcium sensor for short-term facilitation7, is present at both synapses. It was unclear why a sensor for facilitation would be present at these and other depressing synapses. We find that at Purkinje cell and vestibular synapses, Syt7 supports facilitation that is normally masked by depression, which can be revealed in wild-type mice but is absent in Syt7 knockout mice. In wild-type mice, facilitation increases with firing frequency and counteracts depression to produce frequency-invariant transmission. In Syt7-knockout mice, Purkinje cell and vestibular synapses exhibit conventional use-dependent depression, weakening to a greater extent as the firing frequency is increased. Presynaptic rescue of Syt7 expression restores both facilitation and frequency-invariant transmission. Our results identify a function for Syt7 at synapses that exhibit overall depression, and demonstrate that facilitation has an unexpected and important function in producing frequency-invariant transmission.