Zhang Liping, Zhou Yuling, Liu Chengwei, Zheng Wu, Yao Zhimo, Wang Qin, Jin Yile, Zhang Shaomin, Chen Weidong, Chen Jiang-Fan
The Molecular Neuropharmacology Lab, School of Optometry and Ophthalmology, Wenzhou Medical University, China; The State Key Laboratory, School of Optometry and Ophthalmology, Wenzhou Medical University, China.
Qiushi Academy of Advanced Studies and College of Biomedical Engineering and Instrumental Science, Zhejiang University, China.
Neuropharmacology. 2020 Nov 1;178:108250. doi: 10.1016/j.neuropharm.2020.108250. Epub 2020 Jul 26.
Volitional control is at the core of brain-machine interfaces (BMI) adaptation and neuroprosthetic-driven learning to restore motor function for disabled patients, but neuroplasticity changes and neuromodulation underlying volitional control of neuroprosthetic learning are largely unexplored. To better study volitional control at annotated neural population, we have developed an operant neuroprosthetic task with closed-loop feedback system by volitional conditioning of population calcium signal in the M1 cortex using fiber photometry recording. Importantly, volitional conditioning of the population calcium signal in M1 neurons did not improve within-session adaptation, but specifically enhanced across-session neuroprosthetic skill learning with reduced time-to-target and the time to complete 50 successful trials. With brain-behavior causality of the neuroprosthetic paradigm, we revealed that proficiency of neuroprosthetic learning by volitional conditioning of calcium signal was associated with the stable representational (plasticity) mapping in M1 neurons with the reduced calcium peak. Furthermore, pharmacological blockade of adenosine A receptors facilitated volitional conditioning of neuroprosthetic learning and converted an ineffective volitional conditioning protocol to be the effective for neuroprosthetic learning. These findings may help to harness neuroplasticity for better volitional control of neuroprosthetic training and suggest a novel pharmacological strategy to improve neuroprosthetic learning in BMI adaptation by targeting striatal A receptors.
自主控制是脑机接口（BMI）适应和神经假体驱动学习的核心，旨在为残疾患者恢复运动功能，但神经可塑性变化以及神经假体学习自主控制背后的神经调节在很大程度上尚未得到探索。为了在注释的神经群体中更好地研究自主控制，我们通过使用光纤光度记录对M1皮质中的群体钙信号进行自主调节，开发了一种带有闭环反馈系统的操作性神经假体任务。重要的是，M1神经元中群体钙信号的自主调节并没有改善会话内的适应性，但特别增强了跨会话的神经假体技能学习，减少了到达目标的时间和完成50次成功试验的时间。通过神经假体范式的脑-行为因果关系，我们发现通过钙信号的自主调节进行神经假体学习的熟练程度与M1神经元中具有降低的钙峰值的稳定表征（可塑性）映射相关。此外，腺苷A受体的药理学阻断促进了神经假体学习的自主调节，并将无效的自主调节方案转变为对神经假体学习有效的方案。这些发现可能有助于利用神经可塑性来更好地自主控制神经假体训练，并提出一种新的药理学策略，通过靶向纹状体A受体来改善BMI适应中的神经假体学习。
