Shoykhet Michael, Middleton Jason W
Department of Pediatrics, Washington University School of Medicine in St. LouisSt. Louis, MO, USA; Department of Pediatrics, St. Louis Children's HospitalSt. Louis, MO, USA.
Department of Cell Biology and Anatomy, School of Medicine, Louisiana State University Health Sciences CenterNew Orleans, LA, USA; Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences CenterNew Orleans, LA, USA.
Front Neural Circuits. 2016 Aug 25;10:68. doi: 10.3389/fncir.2016.00068. eCollection 2016.
Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and population level activity in the basal ganglia that may contribute to motor dysfunction after injury. Combination of deficits in sensory and motor thalamocortical circuit function may negatively impact sensorimotor integration in CA survivors. Modulation of abnormal activity patterns post-injury may represent a novel therapeutic target to improve neurologic function in survivors.
皮层中感觉信息处理的正常成熟需要在发育调控的关键期内有模式化的突触活动。在早期发育过程中，自发突触活动建立所需的突触输入模式，而在后期发育中，它影响依赖感觉经验的神经元放电模式。丘脑皮质神经元在调节从外周到皮层的模式化感觉信息流中占据关键位置。异常的丘脑皮质输入可能会永久性地影响皮质神经元回路的组织和功能，尤其是在关键发育窗口期间发生时。我们研究了发育中的大鼠心脏骤停（CA）相关的全脑缺氧缺血对体感丘脑皮质神经元的自发和诱发放电以及运动丘脑皮质回路中大规模相关性的影响。CA损伤大鼠的平均自发和感觉诱发放电率活动及变异性更高。此外，未受伤大鼠的自发和感觉诱发活动及变异性是相关的，但CA大鼠的神经元中不相关。腹后内侧核（VPm）神经元的异常活动模式持续到成年期。此外，我们发现基底神经节内苍白球内核（EPN）的神经元在损伤后放电率较低，但变异性较高且爆发放电水平较高。EPN和运动皮层（MCx）之间局部场电位（LFP）的相关功率水平也因损伤而受到破坏。我们的研究结果表明，发育过程中的缺氧缺血损伤会导致从丘脑到皮层的异常自发和感觉刺激诱发输入模式。异常的丘脑输入可能会永久性地并有害地影响皮质回路的组织和感觉信息的处理。缺氧缺血损伤还会导致基底神经节中单个神经元和群体水平的异常活动，这可能导致损伤后运动功能障碍。感觉和运动丘脑皮质回路功能缺陷的组合可能会对CA幸存者的感觉运动整合产生负面影响。损伤后异常活动模式的调节可能代表改善幸存者神经功能的新治疗靶点。
