Two classes of excitatory synaptic responses in rat thalamic reticular neurons

Two classes of excitatory synaptic responses in rat thalamic reticular neurons
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DOI:
10.1152/jn.01121.2015
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发表时间:
2016-09-01
影响因子:
2.5
通讯作者:
Huguenard, John R.
Huguenard, John R.
中科院分区:
医学3区
文献类型:
--
作者:
Deleuze, Charlotte;Huguenard, John R.

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丘脑网状核(nRt)由GABA能细胞组成,对背侧丘脑中的中继神经元提供抑制,接受来自新皮层和丘脑的兴奋。这两条兴奋性通路促进丘脑皮层神经元的反馈或前馈抑制,有助于感觉处理和节律产生。虽然nRt内的突触抑制已被仔细表征,但关于突触兴奋的生物物理学知之甚少。为了表征nRt的丘脑皮质和皮质丘脑连接的功能特性,我们记录了最小的电诱发兴奋性突触后电流从nRt细胞在体外。层次聚类算法区分两种类型的事件。1型事件具有较大幅度和较快动力学,主要由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体介导,而2型反应具有更突出的N-甲基-D-天冬氨酸(NMDA)受体贡献。1型反应表现出低于正常的轴突传播和成对的脉冲抑制,与丘脑皮质输入一致。此外,反应动力学类似于1型事件引起的谷氨酸介导的激活丘脑神经元。与此相反,2型反应,可能会出现从皮质丘脑输入,具有较大的NMDA电导和弱Mg 2+依赖性块,这表明NMDA受体是至关重要的皮质兴奋的网状神经元。NMDA受体的长期作用将促进网状细胞爆发性放电,并对中继神经元产生强大的抑制输出,这些神经元被认为在触发癫痫中很重要。这项工作提供了第一个完整的电压钳分析的动力学和电压依赖性的AMPA和NMDA反应的丘脑皮层和皮质丘脑突触的nRt和将是至关重要的优化生物现实的神经网络模型的丘脑皮层电路相关的感觉处理和丘脑皮层振荡。
The thalamic reticular nucleus (nRt), composed of GABAergic cells providing inhibition of relay neurons in the dorsal thalamus, receives excitation from the neocortex and thalamus. The two excitatory pathways promoting feedback or feedforward inhibition of thalamocortical neurons contribute to sensory processing and rhythm generation. While synaptic inhibition within the nRt has been carefully characterized, little is known regarding the biophysics of synaptic excitation. To characterize the functional properties of thalamocortical and corticothalamic connections to the nRt, we recorded minimal electrically evoked excitatory postsynaptic currents from nRt cells in vitro. A hierarchical clustering algorithm distinguished two types of events. Type 1 events had larger amplitudes and faster kinetics, largely mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, whereas type 2 responses had more prominent N-methyl-D-aspartate (NMDA) receptor contribution. Type 1 responses showed subnormal axonal propagation and paired pulse depression, consistent with thalamocortical inputs. Furthermore, responses kinetically similar to type 1 events were evoked by glutamate-mediated activation of thalamic neurons. Type 2 responses, in contrast, likely arise from corticothalamic inputs, with larger NMDA conductance and weak Mg2+-dependent block, suggesting that NMDA receptors are critical for the cortical excitation of reticular neurons. The long-lasting action of NMDA receptors would promote reticular cell burst firing and produce powerful inhibitory output to relay neurons proposed to be important in triggering epilepsy. This work provides the first complete voltage-clamp analysis of the kinetics and voltage dependence of AMPA and NMDA responses of thalamocortical and corticothalamic synapses in the nRt and will be critical in optimizing biologically realistic neural network models of thalamocortical circuits relevant to sensory processing and thalamocortical oscillations.