Enhancement of synaptic transmission and nociceptive behaviour in HPC‐1/syntaxin 1A knockout mice following peripheral nerve injury

Abstract

Our previous analysis of HPC-1/syntaxin 1A knockout (KO) mice indicated that HPC-1/syntaxin 1A plays an important role in the synaptic plasticity of the hippocampus in vitro and learning behaviour in vivo. In order to gain further insights into the physiological functions of HPC-1/syntaxin 1A, we studied the changes in the plasticity of synaptic transmission in the superficial dorsal horn of the spinal cord following a peripheral nerve injury in HPC-1/syntaxin 1A KO and wild-type (WT) mice. The von Frey filament test revealed that partial ligation of the sciatic nerve caused neuropathic pain in both WT and KO mice. However, KO mice showed significant enhancement of mechanical allodynia as compared with WT mice. Tight-seal whole-cell recordings were obtained from neurons in the superficial dorsal horn of the spinal cord slices. Electrical stimulus-evoked excitatory postsynaptic currents (EPSCs), asynchronous EPSCs (aEPSCs) in the presence of strontium, and spontaneously occurring miniature EPSCs (mEPSCs) were analysed. Prior to peripheral nerve ligation, no significant differences were observed in the properties of evoked EPSCs, aEPSCs and mEPSCs in KO and WT mice. Seven-14 days after partial ligation, the amplitude of evoked EPSCs and the frequency of aEPSCs and mEPSCs in KO mice were significantly greater than those in WT mice; however, the amplitude of aEPSCs and mEPSCs remained unchanged in both groups. Enhanced allodynia behaviour and significant enhancement of excitatory synaptic transmission following peripheral nerve ligation in KO mice suggest that HPC-1/syntaxin 1A might play a role in synaptic plasticity in the nociceptive pathway.

Methamphetamine‐induced neuroinflammation and neuronal dysfunction in the mice hippocampus: preventive effect of indomethacin

“…In fact, we showed alterations in proteins implicated in synapse and axonal transport, such as a decrease in syntaxin‐1 protein levels. It is known that this protein plays an important role in learning behavior in vivo (Takasusuki et al. , 2007).…”

“…In fact, we showed alterations in proteins implicated in synapse and axonal transport, such as a decrease in syntaxin-1 protein levels. It is known that this protein plays an important role in learning behavior in vivo (Takasusuki et al, 2007). Indeed, the formation of long-term potentiation is associated with an increase in levels of syntaxin-1 that occur with the augment of depolarization-induced glutamate release, which in turn leads to the propagation of synaptic plasticity (Helme-Guizon et al, 1998).…”

HPC‐1/syntaxin 1A gene knockout mice show abnormal behavior possibly related to a disruption in 5‐HTergic systems

“…1C, the ASR was also significantly enhanced in STX1A −/− mice, suggesting hypersensitivity to auditory stimuli. We recently reported that STX1A −/− mice showed enhanced allodynia and hypersensitivity to painful stimuli (Takasusuki et al. , 2007).…”

Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage

“…Presynaptic functional changes after peripheral nerve injury that increase synaptic strength include alterations in the synthesis of transmitters and neuromodulators (Obata et al 2003) and in calcium channel density (Hendrich et al 2008, Li et al 2004). Postsynaptic changes involve phosphorylation of N-methyl-D-aspartate (NMDA) subunits (Ultenius et al 2006) and increased receptor density due to trafficking and enhanced synthesis of ion channels and scaffold proteins (Cheng et al 2008, Iwata et al 2007, Miyabe et al 2006, Takasusuki et al 2007, Tao et al 2003). Drugs that attenuate central sensitization by acting on calcium channel subunits to decrease transmitter release and on NMDA channels to reduce transmitter action (Chizh et al 2007; Jorum et al 2003) are effective treatment options in neuropathic pain (Dworkin et al 2007).…”