徐天乐博士简介

GABA and glycine co-release and cross-talk

Using dissociated rat dorsal horn spinal neurons with attached presynaptic terminal boutons, we have characterized the co-release of GABA and glycine as well as the cross-talk between their corresponding activated receptors. There are many outstanding questions. Does the co-release of GABA and glycine also occur in adult neurons, similar to that found for the developing synapses on these spinal neurons isolated from young animals? How do the effects of the two transmitters summate? What are the pre- and postsynaptic mechanisms that determine the relative proportion and the variability of GABA vs glycine component of synaptic transmission? What is the physiological significance of co-transmission? Do drugs acting at one receptor shift the synaptic influence towards the other transmitters? Our current projects are aiming at answering these questions.

Chloride homeostasis and synaptic plasticity and neural development

GABA and glycine exert excitatory actions in early developing CNS neurons, but become inhibitory in mature neurons. It has been proposed that the excitatory actions of GABA and glycine could play a tropic role in promoting synapse maturation. In addition, the excitatory actions of GABA have been implicated in the pathophysiology of epilepsy, stroke and neuronal injury. We are interested in understanding: 1) regulatory mechanisms controlling chloride homeostasis in neurons; 2) physiological roles of the excitatory actions of GABA and glycine on synaptic plasticity and neural development; 3) how dysfunction of chloride homeostasis may contribute to such neurological diseases as epilepsy, depression, neuronal injury, cerebral ischemia and Alzheimer's disease, and how these neuronal disorders can be prevented by GABAergic and glycinergic drugs

Cross-talk between glutamatergic and inhibitory synapses

Induction of long-term synaptic modifications usually depends on a rise in intracellular Ca²⁺ of the postsynaptic neuron. However, except during the early postnatal period when GABA and glycine are depolarizing, activation of GABAergic and glycinergic synapses does not increase postsynaptic Ca²⁺. An important question for understanding the plasticity of inhibitory synapses is where does Ca²⁺ required for synaptic plasticity come from. We have recently demonstrated that activation of Ca²⁺-permeable AMPA and NMDA receptors transiently facilitates glycine response in rat spinal neurons. Moreover, we found that GABA_A response is also regulated by NMDA receptor activation. These findings suggest that co-activation of glutamatergic synapses might play a role in induction of long-term modification at inhibitory synapses. On the other hand, the roles of inhibitory synaptic potentials in regulating plasticity at excitatory synapses have long been recognized. For example, calcineurin-mediated LTD of GABAergic inhibition underlies the increased excitability of CA1 neurons associated with LTP. We are interested in understanding the cellular and molecular basis and functional consequences of cross-talk between glutamatergic and inhibitory synapses.

Publications

Wu, L., Duan, B., Mei, Y., Gao, J., Chen, J., Zhuo, M., Xu, L., Wu, M., and Xu, T. (2004) Characterization of Acid-sensing Ion Channels in Dorsal Horn Neurons of Rat Spinal Cord. J. Biol. Chem. 279(42): 43716-43724 . [Abstract]

Gao, J., Wu, L., Xu, L., and Xu, T. (2004) Properties of the proton-evoked currents and their modulation by Ca(2+) and Zn(2+) in the acutely dissociated hippocampus CA1 neurons. Brain Res. 1017(1-2):197-207 [Abstract]

Xiong, W., Wei, H., Xiang, X., Cao, J., Dong, Z., Wang, Y., Xu, T., and Xu L. (2004) The effect of acute stress on LTP and LTD induction in the hippocampal CA1 region of anesthetized rats at three different ages. Brain Res. 1005(1-2):187-192 [Abstract]

Li, Y., Wu, L., Legendre, P., and Xu, T. (2003) Asymmetric cross-inhibition between GABA_A and glycine receptors in rat spinal dorsal horn neurons. J Biol Chem. 278(40): 38637-38645 [Abstract]

Li, YF., Wu, L., Li, Y., Xu, L., and Xu, T. (2003) Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons. J Physiol. 552(Pt 1): 73-87 [Abstract]

Nie, D., Zhou, Z., Ang, B., Teng, F., Xu, G., Xiang, T., Wang, C., Zeng, L., Takeda, Y., Xu, T., Ng, Y., Faivre-Sarrailh, C., Popko, B., Ling, E., Schachner, M., Watanabe, K., Pallen, C., Tang, B., and Xiao, Z. (2003) Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization. EMBO J. 22(21): 5666-5678 [Abstract]

Li Y, Li YF, Xu TL. Amiloride inhibition of glycinergic miniature IPSCs in mechanically dissociated rat spinal neurons. Neurosci Lett. 2003 Sep 25;349(1):17-20.[Abstract]

Liu, Y., Zhang, G., Hou, X., and Xu, T. (2003) Two types of calcium channels regulating activation of proline-rich tyrosine kinase 2 induced by transient brain ischemia in rat hippocampus.   Neurosci Lett. 348(3): 127-130 [Abstract]

Li, YF., Li, Y., and Xu, T..  (2003) Inhibition of glycine response by amiloride in rat spinal neurons. Neurosci Lett. 345(3): 173-176 [Abstract]

Liu, Y., Hou, X., Zhang, G., and Xu, T.  (2003) L-type voltage-gated calcium channel attends regulation of tyrosine phosphorylation of NMDA receptor subunit 2A induced by transient brain ischemia. Brain Res. 972(1-2): 142-148 [Abstract]

Wu, Z., and Xu, T.  (2003) Taurine-evoked chloride current and its potentiation by intracellular Ca2+ in immature rat hippocampal CA1 neurons. Amino Acids. 24(1-2): 155-161[Abstract]

Zhang, Z., Lu, H., Dong, X., Liu, J., and Xu, T.  (2002) Kinetics of etomidate actions on GABA(A) receptors in the rat spinal dorsal horn neurons. Brain Res. 953(1-2): 93-100 [Abstract]

Dong, X., and Xu, T.   (2002) The actions of propofol on gamma-aminobutyric acid-A and glycine receptors in acutely dissociated spinal dorsal horn neurons of the rat. Anesth Analg. 95(4): 907-914 [Abstract]

Lu, H., and Xu, T.  (2002) The general anesthetic pentobarbital slows desensitization and deactivation of the glycine receptor in the rat spinal dorsal horn neurons. J Biol Chem. 277(44): 41369-41378 [Abstract]

Gao, J., Zhang, J., and Xu, T.  (2002) Modulation of serotonergic projection from dorsal raphe nucleus to basolateral amygdala on sleep-waking cycle of rats. Brain Res. 945(1): 60-70. [Abstract]

Dong, X., and Xu, T.  (2002) Radix paeoniae rubra suppression of sodium current in acutely dissociated rat hippocampal CA1 neurons. Brain Res. 940(1-2): 1-9 [Abstract]

Wu, L., Li, Y., and Xu, T.  (2002) Co-release and interaction of two inhibitory co-transmitters in rat sacral dorsal commissural neurons. Neuroreport. 13(7): 977-81 [Abstract]

Li, Y., and Xu, T.   (2002) State-dependent cross-inhibition between anionic GABA(A) and glycine ionotropic receptors in rat hippocampal CA1 neurons. Neuroreport. 13(2): 223-226 [Abstract]

Wu, L., Lu, Y., and Xu, T.   (2001) A novel mechanical dissociation technique for studying acutely isolated maturing Drosophila central neurons. J Neurosci Methods. 108(2): 199-206 [Abstract]