Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Center for the Neural Basis of Cognition, Pittsburgh, PA, 15213, USA.
Adv Sci (Weinh). 2024 Jul;11(27):e2308212. doi: 10.1002/advs.202308212. Epub 2024 Mar 2.
Substantial evidence has shown that the Circadian Locomotor Output Cycles Kaput (Clock) gene is a core transcription factor of circadian rhythms that regulates dopamine (DA) synthesis. To shed light on the mechanism of this interaction, flexible multielectrode arrays (MEAs) are developed that can measure both DA concentrations and electrophysiology chronically. The dual functionality is enabled by conducting polymer PEDOT doped with acid-functionalized carbon nanotubes (CNT). The PEDOT/CNT microelectrode coating maintained stable electrochemical impedance and DA detection by square wave voltammetry for 4 weeks in vitro. When implanted in wild-type (WT) and Clock mutation (MU) mice, MEAs measured tonic DA concentration and extracellular neural activity with high spatial and temporal resolution for 4 weeks. A diurnal change of DA concentration in WT is observed, but not in MU, and a higher basal DA concentration and stronger cocaine-induced DA increase in MU. Meanwhile, striatal neuronal firing rate is found to be positively correlated with DA concentration in both animal groups. These findings offer new insights into DA dynamics in the context of circadian rhythm regulation, and the chronically reliable performance and dual measurement capability of this technology hold great potential for a broad range of neuroscience research.
大量证据表明，生物钟基因（Clock）是调节多巴胺（DA）合成的核心转录因子。为了阐明这种相互作用的机制，开发了灵活的多电极阵列（MEA），可以长期测量 DA 浓度和电生理学。通过掺杂酸功能化碳纳米管（CNT）的导电聚合物 PEDOT 实现了这种双重功能。PEDOT/CNT 微电极涂层在体外保持稳定的电化学阻抗和通过方波伏安法检测 DA 长达 4 周。当植入野生型（WT）和 Clock 突变（MU）小鼠时，MEA 以高时空分辨率测量了 4 周的紧张型 DA 浓度和细胞外神经活动。在 WT 中观察到 DA 浓度的昼夜变化，但在 MU 中没有，并且在 MU 中 DA 基础浓度较高，可卡因诱导的 DA 增加较强。同时，发现纹状体神经元的放电率与两组动物的 DA 浓度呈正相关。这些发现为生物钟节律调节背景下的 DA 动力学提供了新的见解，并且该技术的长期可靠性能和双重测量能力为广泛的神经科学研究提供了巨大的潜力。
