Bidirectional Long-Term Synaptic Zinc Plasticity at Mouse Glutamatergic Synapses

Abstract

In many excitatory synapses, synaptic zinc is co-released with glutamate to modulate neurotransmission. Synaptic zinc modulates the responsiveness of auditory cortex to sound, and synaptic zinc levels and signaling are modulated by sensory experience, termed zinc plasticity. The mechanisms underlying zinc plasticity remain unknown. We discovered that high- and low-frequency electrical stimulation of dorsal cochlear nucleus synapses reduces and increases synaptic zinc signaling, respectively. This bidirectional zinc plasticity is evidenced by changes in zinc inhibition of AMPA and NMDA receptor activity. Increases and decreases in zinc signaling require activation of Group 1 metabotropic glutamate receptors (mGluRs). Activation of Group 1 mGluRs with a higher agonist concentration increases presynaptic zinc levels and postsynaptic zinc signaling, whereas activation with a lower concentration reduces zinc levels and signaling. Sound-induced zinc plasticity also requires Group 1 mGluRs. Our results reveal the mechanisms underlying synaptic zinc plasticity, elicited by either synaptic activity or sound experience.