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The Journal of Neuroscience, December 7, 2005, 25(49):11385-11395; doi:10.1523/JNEUROSCI.2378-05.2005

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Cellular/Molecular
Noradrenaline Triggers Multivesicular Release at Glutamatergic Synapses in the Hypothalamus

Grant R. J. Gordon and Jaideep S. Bains

Hotchkiss Brain Institute and the Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada, T2N 4N1

The origin of large-amplitude miniature EPSCs (mEPSCs) at central synapses remains to be firmly established. Here, we show that at excitatory synapses onto magnocellular neurosecretory cells in the hypothalamus, noradrenaline induces a rapid and robust increase in mEPSC amplitude that requires ₁-adrenoceptor activation but is impervious to postsynaptic manipulations that block the putative insertion of AMPA receptors. In response to noradrenaline, mEPSCs exhibit a putative multimodal amplitude histogram distribution that is not attibutable to random temporal summation, the unveiling of a quiescent synapse, or the release of large vesicles. Large-amplitude mEPSCs are sensitive to a high dose of ryanodine and are associated with an enhanced glutamate cleft concentration. Together, these data are consistent with the hypothesis that large-amplitude mEPSCs result from the synchronous release of multiple vesicles via rapid presynaptic calcium expulsion from intracellular stores.

Key words: synchronization; synaptic; glutamate; slice; norepinephrine; noradrenaline; hypothalamus

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Received June 9, 2005; revised October 18, 2005; accepted October 18, 2005.

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