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© The Rockefeller University Press, 0021-9525/2000//1325 $5.00
The Journal of Cell Biology, Volume 149, Number 7, , 2000 1325-1334

Brief Report

Role of Egr1 in Hippocampal Synaptic Enhancement Induced by Tetanic Stimulation and Amputation



Feng Weia, Zao C. Xuc, Zhican Qub, Jeffrey Milbrandtb, and Min Zhuoa

a Departments of Anesthesiology, Anatomy and Neurobiology
b Department of Pathology, Washington University, St. Louis, Missouri 63110
c Department of Anatomy, Indiana University, Indianapolis, Indiana 46202
Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 S. Euclid Avenue, St. Louis, MO 63110.(314) 362-8571(314) 747-0416

zhuom{at}morpheus.wustl.edu

Hippocampal neurons fire spikes when an animal is at a particular location or performs certain behaviors in a particular place, providing a cellular basis for hippocampal involvement in spatial learning and memory. In a natural environment, spatial memory is often associated with potentially dangerous sensory experiences such as noxious or painful stimuli. The central sites for such pain-associated memory or plasticity have not been identified. Here we present evidence that excitatory glutamatergic synapses within the CA1 region of the hippocampus may play a role in storing pain-related information. Peripheral noxious stimulation induced excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal cells in anesthetized animals. Tissue/nerve injury caused a rapid increase in the level of the immediate-early gene product Egr1 (also called NGFI-A, Krox24, or zif/268) in hippocampal CA1 neurons. In parallel, synaptic potentiation induced by a single tetanic stimulation (100 Hz for 1 s) was enhanced after the injury. This enhancement of synaptic potentiation was absent in mice lacking Egr1. Our data suggest that Egr1 may act as an important regulator of pain-related synaptic plasticity within the hippocampus.

Key Words: Egr1 • NMDA • LTP • pain • hippocampus

© 2000 The Rockefeller University Press

Abbreviations used in this paper: ACSF, artificial cerebrospinal fluid; DG, dentate gyrus; EPSPs, excitatory postsynaptic potentials; IEGs, immediate-early genes; LTD, long-term depression; LTP, long-term potentiation.


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