An in vivo mouse model of long-term potentiation at synapses between primary afferent C-fibers and spinal dorsal horn neurons: essential role of EphB1 receptor

doi:10.1186/1744-8069-5-29

Molecular Pain

Volume 5

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Han Y
Li HC
Adams B
Zheng JH
Wu YP
Henkemeyer M
Song XJ

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Song XJ
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Research

An in vivo mouse model of long-term potentiation at synapses between primary afferent C-fibers and spinal dorsal horn neurons: essential role of EphB1 receptor

Wen-Tao Liu¹^,2^* , Yuan Han¹^,2^* , Hao-Chuan Li² , Brandt Adams² , Ji-Hong Zheng² , Yong-Ping Wu¹ , Mark Henkemeyer³ and Xue-Jun Song¹^,2^,4

¹Jiangsu Province Key Laboratory of Anesthesiology and Center for Pain Research and Treatment, Xuzhou Medical College, Xuzhou, Jiangsu 221002, PR China

²Department of Neurobiology, Parker University Research Institute, 2500 Walnut Hill Lane, Dallas, Texas 75229, USA

³Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

⁴Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi 710032, PR China

author email corresponding author email* Contributed equally

Molecular Pain 2009, 5:29doi:10.1186/1744-8069-5-29


Published:	12 June 2009

Abstract

Background

Long-term potentiation (LTP), a much studied cellular model of synaptic plasticity, has not been demonstrated at synapses between primary afferent C-fibers and spinal dorsal horn (DH) neurons in mice in vivo. EphrinB-EphB receptor signaling plays important roles in synaptic connection and plasticity in the nervous system, but its role in spinal synaptic plasticity remains unclear.

Results

This study characterizes properties of LTP at synapses of C-fibers onto neurons in the superficial DH following high-frequency stimulation (HFS) of a peripheral nerve at an intensity that activates C-fibers and examines associated activation of Ca²⁺/calmodulin-activated protein kinase II (p-CaMKII), extracellular signal-regulated kinase (p-ERK) and the cyclic AMP response element binding protein (p-CREB) and expression of c-Fos, and it investigates further roles for the EphB1 receptor in LTP. HFS induced LTP within 5 min and lasts for 3–8 h during the period of recording and resulted in upregulation of p-CaMKII, p-ERK and p-CREB protein levels in the spinal cord and expression of c-Fos in DH. Intrathecal pretreatment of MK-801 or EphB2-Fc prevented LTP and significantly reduced upregulation of p-CaMKII, p-ERK, p-CREB and c-Fos. Further, targeted mutation of EphB1 receptor prevented induction of LTP and associated increases in phosphorylation of CaMKII, ERK, and CREB.

Conclusion

This study provides an in vivo mouse model of LTP at synapses of C-fibers onto the superficial DH neurons that will be valuable for studying the DH neuron excitability and their synaptic plasticity and hyperalgesia. It further takes advantage of examining functional implications of a specific gene targeted mice and demonstrates that the EphB1 receptor is essential for development of LTP.