A Scaffolder at the Active Zone Uncovered

RESEARCH HIGHLIGHTS

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Educational efforts • IBRO-edu: http://www.ibroedu.org IBRO — the International Brain Research Organization — is undertaking an ambitious project on its recently relaunched website. ‘IBRO-edu’ is a web resource that, in the short term, aims to provide a registry of educational resources related to neuroscience that are already available on the internet. In the longer term, IBRO intends to add to the SYNAPTIC PHYSIOLOGY educational tools by soliciting and creating new content — presumably to fill in any gaps that are left A scaffolder at the active zone uncovered. The creators of the site are inviting authors of Successful synaptic transmission involves intricate releasable pool’(RRP). The authors found that the RRP α–/– educational material that is interactions of an array of proteins at the active zone. was reduced by 50% in RIM1 synapses, and that posted on the Web to How these biochemical interactions are translated into there was no evidence for a deficiency in subsequent submit it for inclusion in physiological output is still largely unknown. Reporting vesicle exocytosis. IBRO-edu. If you have an in Neuron,Calakos and colleagues provide a detailed Having established RIM1α as a priming factor, educational website that analysis of the molecular mechanism whereby an active Calokos et al. turned to examine the effect of RIM1α could be included, you can zone protein, RIM1α,regulates neurotransmitter deficiency on short-term plasticity. They found that register it online. The quality α–/– of the resources that are release. when RIM1 synapses were challenged with high- included will be ensured by RIM1α is localized at the presynaptic active zone and frequency stimulus trains, they could sustain responses the editorial committee, has been implicated in short- and long-term plasticity. It throughout, whereas there was a 50% reduction in EPSC headed by the Editor-in- contains several protein-binding domains, and is amplitude in wild-type cultures. Intriguingly, although Chief of IBRO-edu, Ante α–/– regarded as a scaffold that interacts with many proteins there was a reduction in initial Pr in RIM1 synapses, Padjen (McGill University, that are involved in the late stages of neurotransmitter P at steady state during high-frequency activity was not Montréal, Canada). r The site is now up and release. Previous studies in mice and worms indicate altered. The authors discovered that this was due not to a running, with some material that RIM1α functions at a stage after the docking of difference in activity-dependent refilling of RRP,but to already included. You can synaptic vesicles at the active zone. However, several an increase in the vesicle release probability. search for material related to regulated steps lead up to transmitter release, including Previous studies have indicated that calcium has an a particular topic, or you can vesicle priming, binding of calcium to presynaptic important role in regulating interactions of RIM1α with browse through subject sensors and fusion of vesicles with the plasma other synaptic proteins. Therefore, Calakos et al. areas. Although coverage is α rather patchy at present, membrane, so which steps require RIM1 ? Calakos et al. suspected that calcium-dependent neurotransmitter α–/– there is some useful material addressed this issue by carrying out a detailed analysis of release might be abnormal in RIM1 synapses. They on the site. However, it will presynaptic funtion in RIM1α-deficient neurons . found that although the overall calcium responsiveness only fulfil its potential if the The authors applied the whole-cell recording was unchanged, the ‘asynchronous’(slow) component of creators of the vast amounts technique to hippocampal autaptic cultures prepared calcium-dependent release was markedly reduced in of educational material from RIM1α–/– mice. They noted that RIM1α–/– synapses RIM1α-deficient synapses. already present on the web had a 50% reduction in excitatory postsynaptic charge, This detailed analysis shows that RIM1α is a key join in by submitting details of their sites to the which could result from a decrease in synapse numbers, regulator of vesicle maturation at the active zone, from organizers. postsynaptic receptor response or the synaptic priming to calcium-dependent triggering of synaptic α–/– IBRO’s shiny new site also probability of neurotransmitter release (Pr). RIM1 vesicle fusion. These results support the idea that has plenty of other essential and wild-type mice had the same number of RIM1α acts as a scaffold to localize various active-zone reading, particularly for synapses, and there was no difference in the amplitude components and to integrate their actions. The study younger neuroscientists. The or frequency of miniature excitatory postsynaptic also provides the first direct link between a synaptic ‘Map and Compass’ section, which bills itself as a ‘survival currents (mEPSCs), so the authors conjectured that protein and the poorly understood processes that –/– guide for young compromised synaptic responses in RIM1α neurons control asynchronous neurotransmitter release. neuroscientists’, contains were probably a result of decreased Pr. Jane Qiu tips on writing a grant, α RIM1 binds directly to Munc13-1, an active zone References and links preparing a poster, protein that is essential for synaptic vesicle priming, so ORIGINAL RESEARCH PAPER Calakos, N. et al. Multiple roles for the active submitting work to journals, Calakos et al. asked whether priming was affected in the zone protein RIM1α in late stages of neurotransmitter release. Neuron 42, and more. α 889–896 (2004) absence of RIM1 .The priming process influences Pr FURTHER READING Rizo, J. & Sudhof, T. C. Snares and Munc18 in synaptic Rachel Jones by determining the number of vesicles in the ‘readily vesicle fusion. Nature Rev. Neurosci. 3, 641–653 (2002)