Inhibitory function of zinc against excitation of hippocampal glutamatergic neurons.

The function of zinc released from the neuron terminals is poorly understood. Here, the action of zinc in excitatory neurotransmission in rat hippocampal CA1 was studied by using in vivo microdialysis. Glutamate concentration in the perfusate was significantly decreased by perfusion with 10-300 microM ZnCl2, suggesting that presynaptic release of glutamate is inhibited by zinc in the CA1. While gamma-amino butyric acid (GABA) concentration in the perfusate was increased by perfusion with zinc. Furthermore, to study the action of zinc in postsynaptic response, the response of the CA1 pyramidal cells in the presence of 50 microM zinc was examined in the entorhinal cortex, which is connected with CA1 pyramidal cells. Perfusion of the hippocampal CA1 with zinc decreased glutamate concentration not only in the CA1, but also in the entorhinal cortex. The increase in glutamate concentration in the entorhinal cortex during perfusion of the CA1 with 50 microM glutamate was inhibited by the addition of zinc in the CA1. Zinc seems to be an inhibitory neuromodulator of glutamate release.