Postsynaptic TrkB-mediated signaling modulates excitatory and inhibitory neurotransmitter receptor clustering at hippocampal synapses
Postsynaptic TrkB-mediated signaling modulates excitatory and inhibitory neurotransmitter receptor clustering at hippocampal synapses
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DOI：
10.1523/jneurosci.4112-03.2004
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发表时间：
2004-03-10
影响因子：
5.3
通讯作者：
Balice-Gordon, RJ
中科院分区：
文献类型：
--
作者：
Elmariah, SB;Crumling, MA;Balice-Gordon, RJ
酪氨酸受体激酶B(TrkB)介导的信号调节海马神经元和其他神经元的突触结构和强度，但其潜在的机制尚不清楚。TrkB全长和截短分布于体外培养的大鼠海马神经元的树突和胞体中。操纵TrkB介导的信号导致突触后NMDA受体(NMDAR)和GABA(A)受体(GABA(A)R)簇的数量和突触定位发生显著变化。BDNF处理后，NMDAR和GABA(A)R簇的数目增加，与突触前终末相对的簇的比例增加。TrkB信号的下调导致受体簇数和突触定位的减少。对BDNF对受体簇影响的时间进程的研究表明，GABA(A)R簇的增加先于NMDAR簇的增加至少12小时。此外，TrkB对NMDAR簇的影响依赖于GABA(A)R的激活。虽然TTX、APV和CNQX治疗没有效果，但用荷包牡丹碱阻断GABA(A)受体可消除BDNF介导的NMDAR簇数和突触定位的增加。相反，外源GABA的应用阻止了BDNF清除所引起的NMDAR簇的减少。综上所述，这些结果表明，TrkB介导的信号调节突触后GABA(A)受体的聚集，并且NMDAR簇的随后上调需要受体活性。因此，TrkB对突触后神经递质簇的影响可能是在发育神经回路中平衡抑制性和兴奋性突触传递的机制的一部分。
Tyrosine receptor kinase B(TrkB)-mediated signaling modulates synaptic structure and strength in hippocampal and other neurons, but the underlying mechanisms are poorly understood. Full-length and truncated TrkB are diffusely distributed throughout the dendrites and soma of rat hippocampal neurons grown in vitro. Manipulation of TrkB-mediated signaling resulted in dramatic changes in the number and synaptic localization of postsynaptic NMDA receptor (NMDAR) and GABA(A) receptor (GABA(A)R) clusters. BDNF treatment resulted in an increase in the number of NMDAR and GABA(A)R clusters and increased the proportion of clusters apposed to presynaptic terminals. Downregulation of TrkB signaling resulted in a decrease in receptor cluster number and synaptic localization. Examination of the time course of the effects of BDNF on receptor clusters showed that the increase in GABA(A)R clusters preceded the increase in NMDAR clusters by at least 12 hr. Moreover, the TrkB-mediated effects on NMDAR clusters were dependent on GABA(A)R activation. Although TTX, APV, and CNQX treatment had no effect, blockade of GABA(A)Rs with bicuculline abolished the BDNF-mediated increase in NMDAR cluster number and synaptic localization. In contrast, application of exogenous GABA prevented the decrease in NMDAR clusters induced by BDNF scavenging. Together, these results suggest that TrkB-mediated signaling modulates the clustering of postsynaptic GABA(A)Rs and that receptor activity is required for a subsequent upregulation of NMDAR clusters. Therefore, TrkB-mediated effects on postsynaptic neurotransmitter clusters may be part of a mechanism that balances inhibitory and excitatory synaptic transmission in developing neural circuits.