Shenzhen Key Lab of Neuropsychiatric Modulation, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Biomaterials. 2012 Jan;33(2):378-94. doi: 10.1016/j.biomaterials.2011.09.083. Epub 2011 Oct 20.
The field of optogenetics has been successfully used to understand the mechanisms of neuropsychiatric diseases through the precise spatial and temporal control of specific groups of neurons in a neural circuitry. However, it remains a great challenge to integrate optogenetic modulation with electrophysiological and behavioral read out methods as a means to explore the causal, temporally precise, and behaviorally relevant interactions of neurons in the specific circuits of freely behaving animals. In this study, an eight-channel chronically implantable optrode array was fabricated and modified with poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate)-poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks (PEDOT/PSS-PVA/PAA IPNs) for improving the optrode-neural tissue interface. The conducting polymer-hydrogel IPN films exhibited a significantly higher capacitance and lower electrochemical impedance at 1 kHz as compared to unmodified optrode sites and showed significantly improved mechanical and electrochemical stability as compared to pure conducting polymer films. The cell attachment and neurite outgrowth of rat pheochromocytoma (PC12) cells on the IPN films were clearly observed through calcein-AM staining. Furthermore, the optrode arrays were chronically implanted into the hippocampus of SD rats after the lentiviral expression of synapsin-ChR2-EYFP, and light-evoked, frequency-dependant action potentials were obtained in freely moving animals. The electrical recording results suggested that the modified optrode arrays showed significantly reduced impedance and RMS noise and an improved SNR as compared to unmodified sites, which may have benefited from the improved electrochemical performance and biocompatibility of the deposited IPN films. All these characteristics are greatly desired in optogenetic applications, and the fabrication method of conducting polymer-hydrogel IPNs can be easily integrated with other modification methods to build a more advanced optrode-neural tissue interface.
光遗传学领域已成功用于通过精确控制神经回路中特定神经元群的时空活动来理解神经精神疾病的发病机制。然而,将光遗传学调制与电生理和行为读取方法相结合,以探索在自由活动动物的特定回路中神经元的因果、时间精确和行为相关的相互作用,仍然是一个巨大的挑战。在这项研究中,我们制备并修饰了一个具有聚(3,4-亚乙基二氧噻吩)/聚(苯乙烯磺酸盐)-聚(聚乙烯醇)/聚(丙烯酸)互穿聚合物网络(PEDOT/PSS-PVA/PAA IPNs)的八通道慢性植入式光纤电极阵列,以改善光纤电极-神经组织界面。与未修饰的光纤电极部位相比,导电聚合物-水凝胶 IPN 薄膜在 1 kHz 时具有更高的电容和更低的电化学阻抗,与纯导电聚合物薄膜相比,具有更好的机械和电化学稳定性。通过钙黄绿素-AM 染色清楚地观察到大鼠嗜铬细胞瘤(PC12)细胞在 IPN 薄膜上的细胞附着和突起生长。此外,在 SD 大鼠海马内慢性植入经过慢病毒表达突触结合蛋白-ChR2-EYFP 的光纤电极阵列后,在自由活动的动物中获得了光诱导、频率依赖性动作电位。电记录结果表明,与未修饰部位相比,修饰后的光纤电极阵列的阻抗和 RMS 噪声显著降低,SNR 得到提高,这可能得益于沉积的 IPN 薄膜电化学性能和生物相容性的提高。所有这些特性在光遗传学应用中都是非常需要的,并且导电聚合物-水凝胶 IPNs 的制造方法可以很容易地与其他修饰方法集成,以构建更先进的光纤电极-神经组织界面。