• glia;
  • glial glutamate transporter (GLT-1);
  • hippocampus;
  • long-term potentiation;
  • voltage-sensitive dye


It is still a matter of dispute whether the expression of hippocampal long-term potentiation (LTP) is due to enhanced transmitter release or enhanced postsynaptic sensitivity. Recently we developed a novel method to monitor synaptically released glutamate. In this method, brain slice preparations are stained with a voltage-sensitive dye RH155 which preferentially stains glial cells, and synaptically induced glial depolarization (SIGD) are optically detected in the presence of the blockers for ionotropic glutamate receptors. We have previously shown that SIGD is due to uptake of synaptically released glutamate by glial glutamate transporters. Here we applied this method to examine change in glutamate release during hippocampal LTP. To examine mossy-CA3 LTP, stimulating electrodes were placed in dentate gyrus and tetanic stimulation was delivered in the presence of 50 µm APV. The amplitude of SIGD after inducing LTP was significantly greater than that in control experiments in which tetanus was not delivered. The amplitude of SIGD after inducing LTP by a brief (3–5 min) application of 50 µm forskolin was also significantly greater than that in control experiments. At the Schaffer-CA1 synapse, the change in the amplitude of SIGD during LTP induced either by 100 Hz tetanus LTP or 200 Hz tetanus was not significantly greater than that of control experiments. These results provide evidence for increased glutamate release from the presynaptic terminals as the expression mechanism for both tetanus-induced and forskolin-induced LTP at mossy-CA3 synapses, and evidence supporting a postsynaptic expression mechanism at Schaffer-CA1 synapses.