Bridging the Translational Gap in Systems Neuroscience: From 1 Circuit Mechanisms to Clinical Therapeutics

Anyin Wang¹Jiale Ye²Jie Li²Xiaoqin Chen¹Qiaoyan Wang³Kunwei Wu^2*

• ¹Chongqing Liangping District People's Hospital, Chongqing, China
• ²Xuzhou Medical University, Xuzhou, China
• ³The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

The advent of optogenetics, chemogenetics, and high-density neural recording technologies has propelled 18 systems neuroscience into a golden age, generating unprecedented mechanistic insights into how defined neural 19 circuits orchestrate behaviour. These tools have allowed us to move beyond correlational observations to establish 20 causal links between specific circuit dynamics and behavioural states. However, a profound and disheartening 21 translational dilemma has emerged: the pace at which these foundational discoveries in model organisms have 22 yielded novel, effective therapeutics for human neuropsychiatric disorders remains glacial. This review argues that 23 this dilemma is not a failure of the science itself but a consequence of a multi-layered gulf between basic discovery 24 and clinical application. This gulf encompasses technological, phenomenological, and biological disparities. We 25 analyse the roots of this impasse and propose a concerted, multi-pronged strategy to bridge it, focusing on 26 back-translation, cross-species behavioural dimensionalization, the development of non-invasive neuromodulation, 27 and the fostering of deeply integrated interdisciplinary collaborations. The path forward requires a fundamental shift 28 in how we design, interpret, and prioritize neural circuit research with translation in mind.