Context-Dependent Modulation of Excitatory Synaptic Strength by Synaptically Released Zinc

• Published in: eNeuro Vol. 4; no. 1; p. ENEURO.0011-17.2017
• Main Authors: Kalappa, Bopanna I, Tzounopoulos, Thanos
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 01.01.2017
• Subjects: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - metabolism; Animals; Auditory Pathways - drug effects; Auditory Pathways - metabolism; Brain Stem - drug effects; Brain Stem - metabolism; Endocannabinoids - metabolism; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Female; Mice, Inbred ICR; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurotransmitter Agents - pharmacology; New Research; Synapses - drug effects; Synapses - metabolism; Synaptic Vesicles - drug effects; Synaptic Vesicles - metabolism; Tissue Culture Techniques; Zinc - metabolism; ZnT3; auditory brainstem; synaptic zinc; short-term plasticity; auditory synapses
• ISSN: 2373-2822; 2373-2822
• DOI: 10.1523/ENEURO.0011-17.2017

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 used electrophysiology 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.