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J. Physiol. 566 (3): 747-758

Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse

Jing Qian1, and Jeffrey L Noebels1

1 Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA

Abstract: Exocytosis of synaptic vesicle contents defines the quantal nature of neurotransmitter release. Here we developed a technique to directly assess exocytosis by measuring vesicular zinc release with the zinc-sensitive dye FluoZin-3 at the hippocampal mossy fibre (MF) synapse. Using a photodiode, we were able to clearly resolve the zinc fluorescence transient ([Zn2+]t) with a train of five action potentials in mouse hippocampal brain slices. The vesicular origin of [Zn2+]t was verified by the lack of zinc signal in vesicular zinc transporter Znt3-deficient mice. Manipulating release probability with the application of neuromodulators such as DCG IV, 4-aminopyridine and forskolin as well as a paired train stimulation protocol altered both the [Zn2+]t and the field excitatory postsynaptic potential (fEPSP) coordinately, strongly indicating that zinc is co-released with glutamate during exocytosis. Since zinc ions colocalize with glutamate in small clear vesicles and modulate postsynaptic excitability at NMDA and GABA receptors, the findings establish zinc as a cotransmitter during physiological signalling at the mossy fibre synapse. The ability to directly visualize release dynamics with zinc imaging will facilitate the exploration of the molecular pharmacology and plasticity of exocytosis at MF synapses.

Received for publication 25 April 2005. Revision received 19 May 2005. Accepted for publication 26 May 2005.

Corresponding author J. L. Noebels: Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Email: jnoebels{at}

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