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Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear. Depressed patients report the alleviation(More)
SNAREs (soluble NSF-attachment protein receptors) are generally acknowledged as central components of membrane fusion reactions, but their precise function has remained enigmatic. Competing hypotheses suggest roles for SNAREs in mediating the specificity of fusion, catalyzing fusion, or actually executing fusion. We generated knockout mice lacking(More)
Neuroligins enhance synapse formation in vitro, but surprisingly are not required for the generation of synapses in vivo. We now show that in cultured neurons, neuroligin-1 overexpression increases excitatory, but not inhibitory, synaptic responses, and potentiates synaptic NMDAR/AMPAR ratios. In contrast, neuroligin-2 overexpression increases inhibitory,(More)
Functional presynaptic vesicles have been subdivided into readily releasable (RRP) and reserve (RP) pools. We studied recycling properties of RRP vesicles through differential retention of FM1-43 and FM2-10 and by varying the time window for FM dye uptake. Both approaches indicated that vesicles residing in the RRP underwent rapid endocytosis (tau(More)
Synapses, the junctions between nerve cells through which they communicate, are formed by the coordinated assembly and tight attachment of pre- and postsynaptic specializations. We now show that SynCAM is a brain-specific, immunoglobulin domain-containing protein that binds to intracellular PDZ-domain proteins and functions as a homophilic cell adhesion(More)
Spontaneous synaptic vesicle fusion is a common property of all synapses. To trace the origin of spontaneously fused vesicles in hippocampal synapses, we tagged vesicles with fluorescent styryl dyes, antibodies against synaptotagmin-1, or horseradish peroxidase. We could show that synaptic vesicles recycle at rest, and after spontaneous exo-endocytosis,(More)
Presynaptic nerve terminals often contain as few as a hundred vesicles and so must recycle them soon after exocytosis to preserve synaptic transmission and presynaptic morphology during repetitive firing. The kinetics and mechanisms of vesicular endocytosis and repriming have therefore been studied. Vesicles in hippocampal nerve terminals can become(More)
The tiny nerve terminals of central synapses contain far fewer vesicles than preparations commonly used for analysis of neurosecretion. Photoconversion of vesicles rendered fluorescent with the dye FM1-43 directly identified vesicles capable of engaging in exo-endocytotic recycling following stimulated Ca(2+) entry. This recycling pool typically contained(More)
High-frequency induced short-term synaptic depression is a common feature of central synapses in which synaptic responses rapidly decrease to a sustained level. A limitation in the availability of release-ready vesicles is thought to be a major factor underlying this phenomenon. Here, we studied the kinetics of vesicle reavailability and reuse during(More)
Currently, there is a limited understanding of the factors that influence the localization and density of individual synapses in the central nervous system. Here we have studied the effects of activity on synapse formation between hippocampal dentate granule cells and CA3 pyramidal neurons in culture, taking advantage of FM1-43 as a fluorescent marker of(More)