老化影响初级视皮层神经元周边抑制的神经机制研究

Abnormally high visual surround suppression accompanies normal aging, while its neural mechanisms are still unclear. Previous electrophysiological studies have revealed a “GABAergic decline” in the neuronal classical receptive field (RF) of the aging visual cortex, but how the extra-classical receptive field (extra-RF) changes during aging is rarely reported. Additionally, the link between specific changes in neural activities and behavioral dysfunction is still unknown due to anaesthetized and paralyzed animals previous used. Our preliminary work found that local inhibition related to neuronal RF, stayed globally intact across age, while lateral inhibition related to neuronal extra-RF potentiated in older adults. We then suggested that there are selective effects of aging on neural extra-RF and RF of the primary visual cortex (V1). In this study, we will be using in-vivo multi-channel extracellular recordings in V1of the behavioral mouse, to analyze age-related changes in both neural RF and extra-RF. Electrophysiological recordings combined with micro-infusions of GABA antagonists and agonists were used to study the effects of potentiated or weakened inhibition strength on both the neural RF and extra-RF of V1 in young and old mice. Our study will provide new insights into the neural mechanisms related to abnormal surround suppression in aging, and to provide a theoretical basis for the rehabilitation of reduced visual functions in older adults.

老化导致视觉周边抑制增强，其具体机制尚不清楚。先前研究发现老年视皮层神经元的经典感受野（RF）发生了“GABAergic衰退”样改变，而老化如何影响非经典感受野（extra-RF）鲜有报道。此外，早期研究多使用麻醉麻痹动物且缺少相应的行为学检测，因而难以建立神经电活动改变与老年视觉感知觉退化的直接联系。我们最近的研究发现，老年神经元RF内的局部抑制不变，而extra-RF对RF的侧抑制显著升高。据此提出“老化选择性地改变神经元RF和extra-RF特性”。本项目拟用清醒小鼠多通道在体胞外记录等方法，阐明老化如何分别影响神经元的RF与extra-RF特性；并通过局部给予GABA激动剂或拮抗剂，验证增强或降低抑制对视皮层神经元RF与extra-RF特性的影响。本工作可望为阐明老年视知觉损伤机制和规律提供新思路，为探索由老化引发的视功能障碍的恢复途径提供一定的理论依据。

阐明神经元活动规律和神经环路的信息处理机制是揭示大脑神经编码机制和病理状态下神经异常编码机制的重要研究目标之一。项目采用啮齿类动物在体胞外多通道记录技术，在清醒小鼠初级感觉皮层和高级皮层，研究了视觉感知觉在老化、酒精毒性、精神分裂症等状态下群体神经元和单个神经元的编码机制，基本完成了项目目标。项目按计划执行，进展较顺利，已发表论文6篇，其中4篇为SCI收录论文，在项目进行中，授权实用新型专利10项，软件著作权1项。培养一名在读研究生。