Deleuze Charlotte, Huguenard John R
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California
J Neurophysiol. 2016 Sep 1;116(3):995-1011. doi: 10.1152/jn.01121.2015. Epub 2016 Jun 8.
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 α-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 Mg(2+)-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.
丘脑网状核(nRt)由γ-氨基丁酸(GABA)能细胞组成,这些细胞对背侧丘脑的中继神经元起抑制作用,它接收来自新皮层和丘脑的兴奋。促进丘脑皮质神经元反馈或前馈抑制的两条兴奋性通路有助于感觉处理和节律产生。虽然nRt内的突触抑制已得到仔细研究,但关于突触兴奋的生物物理学却知之甚少。为了表征丘脑皮质和皮质丘脑与nRt连接的功能特性,我们在体外记录了nRt细胞最小电诱发的兴奋性突触后电流。一种分层聚类算法区分了两种类型的事件。1型事件具有较大的振幅和更快的动力学,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型反应表现出轴突传导异常和双脉冲抑制,与丘脑皮质输入一致。此外,谷氨酸介导的丘脑神经元激活可诱发动力学上类似于1型事件的反应。相比之下,2型反应可能来自皮质丘脑输入,具有较大的NMDA电导和较弱的镁(Mg2+)依赖性阻断,这表明NMDA受体对网状神经元的皮质兴奋至关重要。NMDA受体的持久作用将促进网状细胞爆发式放电,并对中继神经元产生强大的抑制输出,这被认为在触发癫痫中很重要。这项工作首次对nRt中丘脑皮质和皮质丘脑突触的AMPA和NMDA反应的动力学和电压依赖性进行了完整的电压钳分析,对于优化与感觉处理和丘脑皮质振荡相关的丘脑皮质回路的生物学现实神经网络模型至关重要。