title: Noradrenaline triggers multivesicular release at glutamatergic synapses in the hypothalamus.
abstract: 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 alpha1-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 attributable 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.
authors.affiliation: Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: Grant R J
authors.initials: GR
authors.lastname: Gordon
authors.forename: Jaideep S
authors.initials: JS
authors.lastname: Bains
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D018698:Glutamic Acid; D009638:Norepinephrine