Synaptic plasticity in the human dentate gyrus

Activity-dependent plasticity is a fundamental feature of most CNS synapses and is thought to be a synaptic correlate of memory in rodents. In humans, NMDA receptors have been linked to verbal memory processes, but it is uncl ear whether NMDA receptor-dependent synaptic plasticity can be recruited fo r information storage in the human CNS. Here we have for the first time analyzed different forms of synaptic plasti city in human hippocampus. In human subjects who show a morphologically int act hippocampus that is not the primary seizure focus, NMDA receptor-depend ent long-term potentiation (LTP) and forskolin-induced long-lasting potenti ation are readily induced at the perforant path-dentate gyrus synapse. In t his group, long-term potentiation could be partially depotentiated by low-f requency stimulation. Because patients with a hippocampal seizure focus showed a marked reduction in verbal memory performance in previous studies, we asked whether synapti c plasticity is similarly affected by the presence of a hippocampal primary seizure focus. We found that the amount of potentiation induced by high-fr equency stimulation or perfusion of forskolin is dramatically reduced in th is patient group. In addition, low-frequency stimulation is not effective i n inducing synaptic depression. In summary, we show that activity-dependent synaptic plasticity with proper ties similar to the rodent is available for information storage in the huma n hippocampus. Because both verbal memory processes and synaptic plasticity are impaired by a hippocampal seizure focus, we suggest that impaired syna ptic plasticity may contribute to deficient declarative memory in human tem poral lobe epilepsy.