Behavioral/systems/cognitive Controlling Bursting in Cortical Cultures with Closed-loop Multi-electrode Stimulation
Behavioral/systems/cognitive Controlling Bursting in Cortical Cultures with Closed-loop Multi-electrode Stimulation
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通讯作者：
D. Wagenaar;R. Madhavan;J. Pine;Steve M. Potter
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作者：
D. Wagenaar;R. Madhavan;J. Pine;Steve M. Potter
高密度分离神经元培养物的主要活动模式之一是全局同步爆发。与体内不同的是，培养物中的神经元群在培养物的整个生命周期（长达 2 年）内保持着由全局爆发主导的活动模式。我们假设持续爆发是由于缺乏其他大脑区域的输入造成的。为了研究这一假设，我们在多电极阵列上培养了来自大鼠胚胎的小而密集的皮层神经元和神经胶质细胞的单层培养物，并使用电刺激来替代传入神经。我们量化了自发活动和几种刺激方案期间培养物放电的突发性。虽然通过单个电极的缓慢刺激会因突发夹带而增加突发性，但快速刺激会降低突发性。将刺激分布在多个电极上，以及通过闭环反馈不断微调刺激强度，大大增强了突发控制。我们得出的结论是，外部施加的电刺激可以替代皮质神经元群的自然输入，将突发主导的活动转变为分散的尖峰，更让人想起体内清醒的皮质。这种控制爆发的非药物方法将成为探索体外神经元群信息处理能力的关键工具，并且在癫痫治疗方面具有潜在的应用。
One of the major modes of activity of high-density cultures of dissociated neurons is globally synchronized bursting. Unlike in vivo, neuronal ensembles in culture maintain activity patterns dominated by global bursts for the lifetime of the culture (up to 2 years). We hypothesize that persistence of bursting is caused by a lack of input from other brain areas. To study this hypothesis, we grew small but dense monolayer cultures of cortical neurons and glia from rat embryos on multi-electrode arrays and used electrical stimulation to substitute for afferents. We quantified the burstiness of the firing of the cultures in spontaneous activity and during several stimulation protocols. Although slow stimulation through individual electrodes increased burstiness as a result of burst entrainment, rapid stimulation reduced burstiness. Distributing stimuli across several electrodes, as well as continuously fine-tuning stimulus strength with closed-loop feedback, greatly enhanced burst control. We conclude that externally applied electrical stimulation can substitute for natural inputs to cortical neuronal ensembles in transforming burst-dominated activity to dispersed spiking, more reminiscent of the awake cortex in vivo. This nonpharmacological method of controlling bursts will be a critical tool for exploring the information processing capacities of neuronal ensembles in vitro and has potential applications for the treatment of epilepsy.