title: Context-Dependent Modulation of Excitatory Synaptic Strength by Synaptically Released Zinc.
abstract: Synaptically released zinc inhibits baseline excitatory neurotransmission; however, the role of this neuromodulator on short-term plasticity during different levels of synaptic activity remains largely unknown. This lack of knowledge prevents our understanding of information transfer across zinc-releasing synapses, including 50% of excitatory synapses in cortical areas. We usedin vitroelectrophysiology in mouse brain slices and discovered that the effects of zinc on excitatory postsynaptic current (EPSC) amplitudes are context-dependent. At lower frequencies of activity, synaptically released zinc reduces EPSC amplitudes. In contrast, at higher stimulation frequencies and vesicular release probability (Pr), zinc inhibits EPSC amplitudes during the first few stimuli but leads to enhanced steady-state EPSC amplitudes during subsequent stimuli. This paradoxical enhancement is due to zinc-dependent potentiation of synaptic facilitation via the recruitment of endocannabinoid signaling. Together, these findings demonstrate that synaptically released zinc is a modulator of excitatory short-term plasticity, which shapes information transfer among excitatory synapses.
authors.affiliation: Departments of Otolaryngology and Neurobiology, University of Pittsburgh , Pittsburgh, PA 15261.
authors.forename: Bopanna I
authors.initials: BI
authors.lastname: Kalappa
authors.affiliation: Departments of Otolaryngology and Neurobiology, University of Pittsburgh , Pittsburgh, PA 15261.
authors.forename: Thanos
authors.identifier: 0000-0003-4583-145X
authors.initials: T
authors.lastname: Tzounopoulos
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008813:Mice, Inbred ICR; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism; D046509:Tissue Culture Techniques; D015032:Zinc / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D063388:Endocannabinoids; D018377:Neurotransmitter Agents; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D015032:Zinc
keywords: ZnT3; auditory brainstem; auditory synapses; short-term plasticity; synaptic zinc