Long-term potentiation in the dentate gyrus is not linked to increased extracellular glutamate concentration

Long-term potentiation (LTP) of excitatory transmission is a likely candida te for the encoding and storage of information in the mammalian brain. Ther e is a general agreement that LTP involves an increase in synaptic strength , but the mechanisms underlying this persistent change are unclear and cont roversial. Synaptic efficacy may be enhanced because more transmitter gluta mate is released or because postsynaptic responsiveness increases or both. The purpose of this study was to examine whether increased extracellular gl utamate concentration was associated with the robust and well-characterized LTP that can be induced in the rat dentate gyrus. To favor the detection o f any putative change in extracellular glutamate associated with LTP, our e xperimental strategy included the following features. I) Two separate serie s of experiments were carried out with animals under pentobarbital or ureth an anesthesia; 2) changes in extracellular concentration of glutamate were monitored continuously by microdialysis coupled to enzyme amperometry; and 3) dialysate glutamate levels and changes in the slope of excitatory postsy naptic potential evoked by activation of the perforant path were recorded p recisely at the same site. Tetanic stimulation of the perforant path increa sed persistently test-evoked responses in the dentate gyrus (by 19 and 14% in barbiturate and urethan group, respectively), but there was no glutamate change either during or after LTP induction and no indication of increased glutamate efflux when low-frequency stimulation was applied. The results d o not rule out a possible contribution of enhanced glutamate exocytosis to LTP induction and/or maintenance because such a presynaptic change may not be detectable extracellularly. However, our findings and other data support ing the notion that neurotransmitter glutamate may hardly leak out of the s ynaptic cleft conflict with the hypothesis that LTP could also involve a br oad synaptic spillover of glutamate.