New technology reveals social-fear circuit

Thursday, December 1, 2016

The Wang Lab developed a technology called Capturing Activated Neuronal Ensembles (CANE) to label, manipulate and transsynaptically trace neural circuits that are transiently activated in behavioral contexts with high efficiency and temporal precision. 

Described Oct. 27 in Neuron, CANE consists of a knockin mouse and engineered viruses designed to specifically infect activated neurons. Using CANE, they selectively labeled neurons that were activated by either fearful or aggressive social encounters in a hypothalamic subnucleus previously known as a locus for aggression. They discovered that social-fear and aggression neurons are intermixed but largely distinct. Optogenetic stimulation of CANE-captured social-fear neurons (SFNs) is sufficient to evoke fear-like behaviors in normal social contexts, whereas silencing SFNs resulted in reduced social avoidance. CANE-based mapping of axonal projections and presynaptic inputs to SFNs further revealed a highly distributed and recurrent neural network. CANE is a broadly applicable technology for dissecting causality and connectivity of spatially intermingled but functionally distinct ensembles.

Read the Nov. 30 news release by the National Institute of Mental Health: Molecular Tool Parses Social Fear Circuit Intertwined with Aggression Hub

Fig. "Green cells" are CANE-captured neurons activated by a previous social fear experience, “red cells” are Fos+ neurons activated by a recent (2nd) social fear experience.