Role of EGR1 in hippocampal synaptic enhancement induced by tetanic stimulation and amputation

Hippocampal neurons fire spikes when an animal is at a particular location or performs certain behaviors in a particular place, providing a cellular b asis for hippocampal involvement in spatial learning and memory. In a natur al environment, spatial memory is often associated with potentially dangero us sensory experiences such as noxious or painful stimuli. The central site s for such pain-associated memory or plasticity have not been identified. H ere we present evidence that excitatory glutamatergic synapses within the C A1 region of the hippocampus may play a role in storing pain-related inform ation. Peripheral noxious stimulation induced excitatory postsynaptic poten tials (EPSPs) in CA1 pyramidal cells in anesthetized animals. Tissue/nerve injury caused a rapid increase in the level of the immediate-early gene pro duct Egr1 (also called NGFI-A, Krox24, or zif/268) in hippocampal CA1 neuro ns. In parallel, synaptic potentiation induced by a single tetanic stimulat ion (100 Hz for 1 s) was enhanced after the injury. This enhancement of syn aptic potentiation was absent in mice lacking Egr1. Our data suggest that E gr1 may act as an important regulator of pain-related synaptic plasticity w ithin the hippocampus.