Enhancing the fidelity of neurotransmission by activity-dependent facilitation of presynaptic potassium currents.

Neurons convey information in bursts of spikes across chemical synapses where the fidelity of information transfer critically depends on synaptic input-output relationship. With a limited number of synaptic vesicles (SVs) in the readily releasable pool (RRP), how nerve terminals sustain transmitter release during intense activity remains poorly understood. Here we report that presynaptic K(+) currents evoked by spikes facilitate in a Ca(2+)-independent but frequency- and voltage-dependent manner.

Septins regulate developmental switching from microdomain to nanodomain coupling of Ca(2+) influx to neurotransmitter release at a central synapse.

Neurotransmitter release depends critically on close spatial coupling of Ca(2+) entry to synaptic vesicles at the nerve terminal; however, the molecular substrates determining their physical proximity are unknown. Using the calyx of Held synapse, where "microdomain" coupling predominates at immature stages and developmentally switches to "nanodomain" coupling, we demonstrate that deletion of the filamentous protein Septin 5 imparts immature synapses with striking morphological and functional features reminiscent of mature synapses. This includes synaptic vesicles tightly localized to active zones, resistance to the slow Ca(2+) buffer EGTA and a reduced number of Ca(2+) channels required to trigger single fusion events.

Action potential evoked transmitter release in central synapses: insights from the developing calyx of Held.

Chemical synapses are the fundamental units that mediate communication between neurons in the mammalian brain. In contrast to the enormous progress made in mapping out postsynaptic contributions of receptors, scaffolding structures and receptor trafficking to synaptic transmission and plasticity, the small size of nerve terminals has largely precluded direct analyses of presynaptic modulation of excitability and transmitter release in central synapses. Recent studies performed in accessible synapses such as the calyx of Held, a giant axosomatic synapse in the sound localization circuit of the auditory brainstem, have provided tremendous insights into how central synapses regulate the dynamic gain range of synaptic transmission.

Activity-dependent changes in temporal components of neurotransmission at the juvenile mouse calyx of Held synapse.

The temporal fidelity of synaptic transmission is constrained by the reproducibility of time delays such as axonal conduction delay and synaptic delay, but very little is known about the modulation of these distinct components. In particular, synaptic delay is not generally considered to be modifiable under physiological conditions. Using simultaneous paired patch-clamp recordings from pre- and postsynaptic elements of the calyx of Held synapse, in juvenile mouse auditory brainstem slices, we show here that synaptic activity (20-200 Hz) leads to activity-dependent increases in synaptic delay and its variance as well as desynchronization of evoked responses.

Developmental transformation of the release modality at the calyx of Held synapse.

Ca(2+) influx through voltage-gated Ca(2+) channels (VGCCs) into nerve terminals triggers vesicular fusion and neurotransmitter release. However, it is unknown whether the coupling between VGCCs and synaptic vesicles (SVs) is developmentally regulated. By paired patch-clamp recordings from the mouse calyx of Held synapse, we show here that injection of a Ca(2+) buffer with slow binding kinetics (EGTA; 10 mm) potently attenuated transmitter release in young terminals [postnatal day 8 (P8)-P12] but produced little effect in older ones (P16-P18), suggesting that SVs in young synapses are loosely coupled to VGCCs, but the coupling tightens spatially during maturation.