Involvement of intracellular Zn²⁺ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse

Physiological significance of synaptic Zn²⁺ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn²⁺ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn²⁺ chelator, suggesting that intracellular Zn²⁺ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn²⁺ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn²⁺ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn²⁺ , which originates in presynaptic Zn²⁺ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn²⁺ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells.