MouseCircuits.org: An online repository to guide the circuit era of disordered affect

Abstract

Affective disorders rank amongst the most disruptive and prevalent psychiatric diseases, resulting in enormous societal and economic burden, and immeasurable personal costs. Novel therapies are urgently needed but have remained elusive. The era of circuit-mapping in rodent models of disordered affect, ushered in by recent technological advancements allowing for precise and specific neural control, has reenergized the hope for precision psychiatry. Here, we present a novel whole-brain cumulative network and critically access the progress made to-date on circuits mediating affective-like behaviors in rodents to seek unifying principles of this cumulative data. We identified 106 original manuscripts in which optogenetics or chemogenetics were used to dissect behaviors related to fear-like, depressive-like or anxiety-like behaviors in rodents. Focusing on the 60 manuscripts that investigated pathways rather than regions, we identified emergent themes. We found that while a few pathways have been validated across similar behaviors and multiple labs, the data is mostly disjointed, with evidence of bidirectional effects of several pathways. Additionally, there is a need for analysis informed by observation prior to perturbation. Given the complex nature of brain connectivity, we argue that the compartmentalized viewpoint that develops as a consequence of fragmented pathway-specific manipulations does not readily lend itself to an integrative picture. To address this, we launched an interactive online consortium,MouseCircuits.org, an open-source platform for consolidated circuit data. This tool aims to support the shared vision of informed circuit dissection that ultimately leads to prevention and treatment of human disorders.