VR1 receptor activation induces glutamate release and postsynaptic firing in the paraventricular nucleus

被引:75
作者
Li, DP
Chen, SR
Pan, HL
机构
[1] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Anesthesiol, Hershey, PA 17033 USA
[2] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA
关键词
D O I
10.1152/jn.00171.2004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neurons in the paraventricular nucleus (PVN) are important in regulating autonomic function through projections to the brain stem and spinal cord. Although the vanilloid receptors (VR1) are present in the PVN, their physiological function is scarcely known. In this study, we determined the role of VR1 receptors in the regulation of synaptic inputs and the excitability of spinally projecting PVN neurons. Whole cell patch-clamp recordings were performed on the PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Capsaicin significantly increased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) without changing the amplitude and decay time constant of mEPSCs. On the other hand, capsaicin had no effect on GABAergic miniature inhibitory postsynaptic currents (mIPSCs). The effect of capsaicin on mEPSCs was abolished by a specific VR1 antagonist, iodo-resiniferatoxin (iodo-RTX), or ruthenium red. Importantly, iodo-RTX per se significantly reduced the amplitude of evoked EPSCs and the frequency of mEPSCs. Removal of extracellular Ca2+, but not Cd2+ treatment, also eliminated the effect of capsaicin on mEPSCs. Furthermore, capsaicin caused a large increase in the firing rate of PVN neurons, and such an effect was abolished in the presence of ionotropic glutamate receptor antagonists. Additionally, the double-immunofluorescence labeling revealed that all of the VR1 immunoreactivity was colocalized with a presynaptic marker, synaptophysin, in the PVN. Thus this study provides the first evidence that activation of VR1 receptors excites preautonomic PVN neurons through selective potentiation of glutamatergic synaptic inputs. Presynaptic VR1 receptors and endogenous capsaicin-like substances in the PVN may represent a previously unidentified mechanism in hypothalamic regulation of the autonomic nervous system.
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收藏
页码:1807 / 1816
页数:10
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