Coincident Pre- and Postsynaptic Activation Induces Dendritic Filopodia via Neurotrypsin-Dependent Agrin Cleavage

SummaryThe synaptic serine protease neurotrypsin is essential for cognitive function, as its deficiency in humans results in severe mental retardation. Recently, we demonstrated the activity-dependent release of neurotrypsin from presynaptic terminals and proteolytical cleavage of agrin at the synapse. Here we show that the activity-dependent formation of dendritic filopodia is abolished in hippocampal neurons from neurotrypsin-deficient mice. Administration of the neurotrypsin-dependent 22 kDa fragment of agrin rescues the filopodial response. Detailed analyses indicated that presynaptic action potential firing is necessary for the release of neurotrypsin, whereas postsynaptic NMDA receptor activation is necessary for the neurotrypsin-dependent cleavage of agrin. This contingency characterizes the neurotrypsin-agrin system as a coincidence detector of pre- and postsynaptic activation. As the resulting dendritic filopodia are thought to represent precursors of synapses, the neurotrypsin-dependent cleavage of agrin at the synapse may be instrumental for a Hebbian organization and remodeling of synaptic circuits in the CNS

Interventions Versus Customer Transactions: An Alternative Test of the Signalling Hypothesis

The intra-daily efficacy of interventions by the Swiss National Bank (SNB) is examined for the 1986–94 period. The paper extends results from earlier studies because it uses the actual intervention exchange rates and all SNB interventions are known to the market. Our test of the signalling hypothesis, which distinguishes between interventions and customer transactions, is similar in spirit to US studies that exploit the informational differences between reported and unreported interventions. A key finding is that only initial interventions matter; customer transactions and subsequent interventions have no influence.exchange rate intervention; signalling hypothesis

Are Interventions Self-Exciting?

It is often argued that interventions provide news on changes in risk premia or in future monetary policy. If so, the timing of interventions offers important information for central bank watchers. One method to study the reaction function of a central bank is to consider whether the duration intervals of past interventions matter for future interventions. The time deformation of interventions is modelled as an autoregressive process following the class of ACD models first proposed by Engle and Russell (1994). The analysis considers the persistence of interventions by the Federal Reserve, the Bundesbank and the Swiss National Bank.Duration; exchange rate intervention

Chemical Functionalization of Calcium Phosphate Bioceramic Surfaces

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