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

Abstract

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.

Hippocampal AMPARs involve the central sensitization of rats with irritable bowel syndrome

“…Wei, Xu, Qu, Milbrandt, & Zhuo (2000) first recorded a hippocampal reaction to peripheral noxious stimulations in adult rats. Zhao reported that in a bee venom‐induced persistent pain animal model, hippocampus LTP was remarkably enhanced (Zhao et al., 2009).…”

Roles of the hippocampal formation in pain information processing

“…Unfortunately, there is still a paucity of basic research exploring pain-related synaptic plasticity in the HF [12,165] . Using in vivo electrophysiology, Wei et al [165] first showed that hippocampal pyramidal cells responded to peripheral noxious stimuli in adult anesthetized rats.…”

“…Unfortunately, there is still a paucity of basic research exploring pain-related synaptic plasticity in the HF [12,165] . Using in vivo electrophysiology, Wei et al [165] first showed that hippocampal pyramidal cells responded to peripheral noxious stimuli in adult anesthetized rats. Then by slice electrophysiology, the authors found that in CA1 neurons, synaptic plasticity of excitatory glutamatergic transmission was altered after tissue injury, reflected as the enhancement of long-term potentiation (LTP),…”

“…There are mainly five papers, in our hands, reporting pain-evoked increase in c-Fos expression in the HF [165,[177][178][179][180] . Aloisi et al [177] investigated, by immunohistochemistry, the effects of a persistent painful stimulus (formalin injection) and restraint stress (immobilization) on cFos expression in the hippocampus and septum of male and female rats.…”

Upregulation of Forebrain NMDA NR2B Receptors Contributes to Behavioral Sensitization after Inflammation

“…Previous studies demonstrated that some hippocampal neurons respond to noxious stimuli, providing a possible candidate for pain-related spatial memory (Wei et al, 2000). We next wanted to know whether NR2B levels in the hippocampus might be affected after inflammation.…”