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At presynaptic active zones, neurotransmitter release is initiated by the opening of voltage-gated Ca²+ channels close to docked vesicles. The mechanisms that enrich Ca²+ channels at active zones are, however, largely unknown, possibly because of the limited presynaptic accessibility of most synapses. Here, we have established a Cre-lox based conditional(More)
Developmental refinement of synaptic transmission can occur via changes in several pre- and postsynaptic factors, but it has been unknown whether the intrinsic Ca2+ sensitivity of vesicle fusion in the nerve terminal can be regulated during development. Using the calyx of Held, a giant synapse in the auditory pathway, we studied the presynaptic mechanisms(More)
Repeated pairings of light and rotation (conditioning) result in persistent changes in excitability of Hermissenda type B and A photoreceptors, which are correlated with pairing-specific reductions in phototactic behavior. Although considerable attention has been devoted to characterization of conditioning-produced neurophysiological changes that occur in(More)
At eye opening, neurons in primary visual cortex (V1) are selective for stimulus features, but circuits continue to refine in an experience-dependent manner for some weeks thereafter. How these changes contribute to the coding of visual features embedded in complex natural scenes remains unknown. Here we show that normal visual experience after eye opening(More)
The large glutamatergic calyx of Held synapse in the auditory brainstem has become a powerful model for studying transmitter release mechanisms, but the molecular bases of presynaptic function at this synapse are not well known. Here, we have used single-cell quantitative PCR (qPCR) to study the developmental expression of all major Synaptotagmin (Syt)(More)
The localization and density of voltage-gated Ca(2+) channels at active zones are essential for the amount and kinetics of transmitter release at synapses. RIM proteins are scaffolding proteins at the active zone that bind to several other presynaptic proteins, including voltage-gated Ca(2+) channel α-subunits. The long isoforms of RIM proteins, which(More)
Focal adhesion kinase (FAK) controls cellular adhesion and motility processes by its tight link to integrin- and extracellular-matrix-mediated signaling. To explore the dynamics of the regulation of FAK, we constructed a FRET-based probe that visualizes conformational rearrangements of the FERM domain of FAK in living cells. The sensor reports on an(More)
Ca(2+)-dependent transmitter release is the most important signaling mechanism for fast information transfer between neurons. Transmitter release takes places at highly specialized active zones with sub-micrometer dimension, which contain the molecular machinery for vesicle docking and -fusion, as well as a high density of voltage-gated Ca(2+) channels. In(More)
The spatial arrangement of Ca2+ channels and vesicles remains unknown for most CNS synapses, despite of the crucial importance of this geometrical parameter for the Ca2+ control of transmitter release. At a large model synapse, the calyx of Held, transmitter release is controlled by several Ca2+ channels in a "domain overlap" mode, at least in young(More)
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