communication mediumForum of Neuroscience of the Federation of European
Neuroscience Societies, FENS 2018
Animals often react to environmental challenge by aversive behavioral adaptations, like stress induced switching from active to passive behavior and anxiety driven threat avoidance. This response pattern is shared by humans with generalized anxiety disorders and treated with benzodiazepines (BZDs). Despite recent advances, the neuronal circuit interactions underlying this form behavioral plasticity and BZD anxiolytics remain poorly understood. Here, we combined forebrain wide c-fos functional maps with circuit physiology to delineate neuronal circuits involved in these processes. We found that circuitry interconnecting the paraventricular thalamus (PVT) and the central amygdala (CE) senses stress and facilitates the switch from active to passive behavior. Deep brain imaging, chemogenetics and optogenetic fMRI suggest that BZDs target the same circuitry, with opposite effects. They block the relay of aversive signals from PVT through the CE, in part by local binding and reshaping intra-CE circuit dynamics. Computationally fusing brain data with genetic studies (QTL, GWAS) related these findings to behavioral genetics. Together, our study links local circuit mechanisms to the genetic control of brain circuitry, behavioral traits and clinical treatment. This delineates a strategy for the identification of biomedically relevant circuit interactions and highlights the importance of thalamo-amygdala circuitry for the pathophysiology of anxiety.