Noradrenaline Triggers Multivesicular Release at Glutamatergic Synapses in the Hypothalamus

• Published in: The Journal of neuroscience Vol. 25; no. 49; pp. 11385 - 11395
• Main Authors: Gordon, Grant R. J, Bains, Jaideep S
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 07.12.2005; Society for Neuroscience
• Subjects: Animals; Cellular/Molecular; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Glutamic Acid - metabolism; Hypothalamus - drug effects; Hypothalamus - metabolism; In Vitro Techniques; Male; Norepinephrine - pharmacology; Norepinephrine - physiology; Rats; Rats, Sprague-Dawley; Receptors, AMPA - agonists; Receptors, AMPA - metabolism; Synapses - drug effects; Synapses - metabolism; Synaptic Vesicles - drug effects; Synaptic Vesicles - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.2378-05.2005

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.