Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus.
Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus.
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DOI：
10.1523/jneurosci.5083-09.2010
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发表时间：
2010-04-14
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影响因子：
--
通讯作者：
Huguenard JR
中科院分区：
文献类型：
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作者：
Paz JT;Christian CA;Parada I;Prince DA;Huguenard JR
局灶性皮质损伤导致皮质神经元及其传出神经元的死亡，并最终导致投射到受影响皮质区域的丘脑皮质中继（TCR）神经元的死亡或损伤。抑制性网状丘脑核（nRT）的神经元接收来自皮质丘脑和丘脑皮质轴突的兴奋性输入，并且因此被这样的损伤去神经支配，然而nRT细胞通常比TCR细胞在更大程度上存活于这些损伤。nRT细胞抑制TCR细胞，调节丘脑皮质传递，并产生脑节律，包括参与丘脑皮质癫痫的脑节律。皮质损伤后nRT的存活和重组将决定损伤后丘脑皮质回路的恢复。然而，幸存者的生理特性和连通性仍然未知。为了研究nRT神经元可能的改变，我们使用大鼠皮质卒中光血栓模型。使用体外膜片钳记录在不同的时间后的光血栓损伤，我们表明，局部中风的躯体感觉皮层诱导长期减少内在兴奋性和诱发的nRT细胞的突触兴奋损伤后的第一周结束。我们发现，损伤大鼠nRT神经元表现出（1）膜输入电阻降低，（2）低阈值钙爆发反应减少，（3）诱发兴奋性突触反应减弱。nRT细胞兴奋性的这种改变可能导致中继核中nRT介导的抑制的丧失，存活TCR细胞的输出增加和丘脑皮质兴奋增强，这可能有助于丘脑和皮质感觉回路的恢复。此外，这种变化可能是适应不良的，导致损伤诱导的癫痫。
Focal cortical injuries result in death of cortical neurons and their efferents and ultimately in death or damage of thalamocortical relay (TCR) neurons that project to the affected cortical area. Neurons of the inhibitory reticular thalamic nucleus (nRT) receive excitatory inputs from corticothalamic and thalamocortical axons and are thus denervated by such injuries, yet nRT cells generally survive these insults to a greater degree than TCR cells. nRT cells inhibit TCR cells, regulate thalamocortical transmission, and generate cerebral rhythms including those involved in thalamocortical epilepsies. The survival and reorganization of nRT following cortical injury would determine recovery of thalamocortical circuits following injury. However, the physiological properties and connectivity of the survivors remain unknown. In order to study possible alterations in nRT neurons, we used the rat photothrombosis model of cortical stroke. Using in vitro patch clamp recordings at various times following the photothrombotic injury, we show that localized strokes in the somatosensory cortex induce long-term reductions in intrinsic excitability and evoked synaptic excitation of nRT cells by the end of the first week after the injury. We find that nRT neurons in injured rats show (1) decreased membrane input resistance, (2) reduced low-threshold calcium burst responses, and (3) weaker evoked excitatory synaptic responses. Such alterations in nRT cellular excitability could lead to loss of nRT-mediated inhibition in relay nuclei, increased output of surviving TCR cells and enhanced thalamocortical excitation, which may facilitate recovery of thalamic and cortical sensory circuits. In addition, such changes could be maladaptive, leading to injury-induced epilepsy.