Exocytosis of vesicular zinc reveals persistent depression of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3-CA1 synapse.
Exocytosis can be directly measured in mammalian brain slices by fluorescence detection of vesicular zinc release. Detection of the low-level evoked zinc signal [Zn]t was first demonstrated at the zinc-rich hippocampal mossy fiber pathway and required the use of high-frequency presynaptic stimulation. Here, we show that release after individual action potentials can be reliably detected even at non-mossy fiber, zinc-poor synapses in the hippocampus, a major enhancement in the temporal resolution of the technique. Short-term facilitation of release properties of zinc-positive CA3-CA1 Schaffer collateral/commissural synapses in the stratum radiatum differ from those at mossy fibers but are similar to those measured for the EPSP [field EPSP (fEPSP)]. The N-type Ca2+ channel toxin omega-conotoxin GVIA inhibited both the [Zn]t and fEPSP equally, and the modulation of neurotransmitter release by neuropeptide Y, baclofen, and adenosine as revealed by [Zn]t closely resembles that measured for the fEPSP. A long-standing controversy in hippocampal synaptic plasticity involves the site of long-term depression (LTD) at these synapses. Using zinc release as a direct marker for exocytotic events and a surrogate marker for glutamate release, we demonstrate that persistent depression of presynaptic release occurs in the late expression of DHPG [(S)-3,5-dihydroxyphenylglycine]-induced LTD at this synapse. The ability to examine release dynamics with zinc fluorescence detection will facilitate exploration of the molecular pharmacology and plasticity of exocytosis at many CNS synapses.
Qian
Jing
J
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
Noebels
Jeffrey L
JL
D000200:Action Potentials / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D027682:Cation Transport Proteins; D003433:Crosses, Genetic; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D015032:Zinc / Q000502:physiology
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D018094:Receptors, Metabotropic Glutamate; C491177:Slc30a3 protein, mouse; D001418:Baclofen; D015032:Zinc; D000241:Adenosine