IMPAIRED TRANSMISSION AT CORTICOTHALAMIC EXCITATORY INPUTS AND INTRATHALAMIC GABAERGIC SYNAPSES IN THE VENTROBASAL THALAMUS OF HETEROZYGOUS BDNF KNOCKOUT MICE
IMPAIRED TRANSMISSION AT CORTICOTHALAMIC EXCITATORY INPUTS AND INTRATHALAMIC GABAERGIC SYNAPSES IN THE VENTROBASAL THALAMUS OF HETEROZYGOUS BDNF KNOCKOUT MICE
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DOI：
10.1016/j.neuroscience.2012.07.005
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发表时间：
2012-10-11
期刊：
影响因子：
3.3
通讯作者：
Lessmann, V.
中科院分区：
文献类型：
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作者：
Laudes, T.;Meis, S.;Lessmann, V.
脑源性神经营养因子(BDNF)除了在突触的发育和成熟中发挥作用外，还在谷氨酸和GABA能突触传递的调节和可塑性中发挥重要作用。在这里，我们使用杂合子BDNF基因敲除(BDNF+/-)小鼠，它长期缺乏野生型(WT)动物大约50%的BDNF，以研究BDNF在调节丘脑腹基复合体(VB)突触传递中的作用。兴奋性传递在VB的谷氨酸能突触至中继神经元，抑制性传递在GABA能突触的丘脑网状核(RTN)和TC神经元之间。BDNF+/-小鼠BDNF表达减少并不影响TC神经元的固有膜特性。然而，TC神经元的记录显示，与WT小鼠相比，BDNF+/-小鼠的微小兴奋性突触后电流(MEPSC)的频率显著降低，而mEPSC的幅度在不同基因型之间没有显著差异。BDNF+/-小鼠皮质丘脑兴奋性突触的突触前损伤还表现为双脉冲比率降低和在40赫兹长时间重复刺激时突触疲劳加剧。对于TC神经元记录的微小抑制性突触后电流(MIPSCs)，敲除动物的频率和幅度都显著降低，同时伴随着延长的衰减时间常数，而WT和BDNF+/-小鼠的抑制性突触的双脉冲抑制和突触疲劳没有显著差异。BDNF+/-动物VB神经元记录到的自发IPSCs(SIPSCs)频率明显降低。然而，应用AMPA和NMDA受体阻断剂后，sIPSCs频率下降的百分比表明，谷氨酸能驱动RTN神经元的作用没有显著差异。综上所述，目前的发现表明，在杂合基因敲除动物中，BDNF水平长期降低到WT水平的50%，强烈减弱丘脑回路中谷氨酸和GABA能突触传递。我们推测，兴奋性和抑制性传递的这种损害可能会对丘脑皮质网络中节律性活动的产生产生深远的影响。(C)2012年IBRO。爱思唯尔有限公司出版。保留所有权利。
Beside its role in development and maturation of synapses, brain-derived neurotrophic factor (BDNF) is suggested to play a critical role in modulation and plasticity of glutamatergic as well as GABAergic synaptic transmission. Here, we used heterozygous BDNF knockout (BDNF+/-) mice, which chronically lack approximately 50% of BDNF of wildtype (WT) animals, to investigate the role of BDNF in regulating synaptic transmission in the ventrobasal complex (VB) of the thalamus. Excitatory transmission was characterized at glutamatergic synapses onto relay (TC) neurons of the VB and intrathalamic inhibitory transmission was characterized at GABAergic synapses between neurons of the reticular thalamic nucleus (RTN) and TC neurons. Reduced expression of BDNF in BDNF+/- mice did not affect intrinsic membrane properties of TC neurons. Recordings in TC neurons, however, revealed a strong reduction in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in BDNF+/- mice, as compared to WT littermates, whereas mEPSC amplitudes were not significantly different between genotypes. A mainly presynaptic impairment of corticothalamic excitatory synapses in BDNF+/- mice was also indicated by a decreased paired-pulse ratio and faster synaptic fatigue upon prolonged repetitive stimulation at 40 Hz. For miniature inhibitory postsynaptic currents (mIPSCs) recorded in TC neurons, both, frequency and amplitude showed a significant reduction in knock-out animals, concurrent with a prolonged decay time constant, whereas paired-pulse depression and synaptic fatigue of inhibitory synapses were not significantly different between WT and BDNF+/- mice. Spontaneous IPSCs (sIPSCs) recorded in VB neurons of BDNF+/- animals showed a significantly reduced frequency. However, the glutamatergic drive onto RTN neurons, as revealed by the percentage reduction in frequency of sIPSCs after application of AMPA and NMDA receptor blockers, was not significantly different. Together, the present findings suggest that a chronically reduced level of BDNF to similar to 50% of WT levels in heterozygous knock-out animals, strongly attenuates glutamatergic and GABAergic synaptic transmission in thalamic circuits. We hypothesize that this impairment of excitatory and inhibitory transmission may have profound consequences for the generation of rhythmical activity in the thalamocortical network. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.