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Molecular Tool Parses Social Fear Circuit Intertwined with Aggression Hub

Science Update

In its debut performance, a powerful new genetic engineering tool has revealed secrets of functionally distinct brain circuits for social fear and aggression in mice. This, even though these sets of neurons seem hopelessly intertwined. The tool, called CANE (Capturing Activated Neuronal Ensembles), helps trace distinct pathways embedded within the brain’s spaghetti-like wiring.

NIMH grantee Fan Wang, Ph.D. , of Duke University, and colleagues, reported on their discovery November 23, 2016 in the journal Neuron.

“CANE promises to be widely adopted, in part, because it uses readily available ‘on-the-shelf’ methods that many neuroscientists are already familiar with,” explained Michelle Freund, Ph.D., of the NIMH Office of Technology Development and Coordination, which funds the project.

CANE provides a window into the cause-and-effect relationship between specific behaviors and brain circuitry. It combines genetically-engineered mice and viruses with optogenetics – which permits specific circuits to be experimentally switched on-and-off by pulses of light. The viruses infect neurons with telltale tracers that visualize circuits when activated by specific behaviors, enabling precise timing and targeting.

For example, the researchers used CANE to discover circuits activated in an experimental situation in which an “intruder” mouse visits the cage of a “resident” male mouse. When the latter characteristically attacked the intruder, CANE visualized activation of a set of neurons for aggression in a particular part of the hypothalamus, which had been previously linked to aggression. In the intruder mice under attack, CANE revealed activation of a set of neurons for social fear. It turned out that the two circuits are anatomically intertwined, sharing only about 10-20 percent of the same cells.   

When the researchers optogenetically switched on the fear circuit in the resident male, it retreated into a corner, demonstrating that the circuit regulates this social behavior. CANE can show either circuit activated in the same mouse, depending upon whether it’s the intruder or the resident.

CANE visualized neurons activated by an earlier social fear encounter (green) and neurons that signal gene activation triggered by a later social fear experience (red).

CANE visualized neurons activated by an earlier social fear encounter (green) and neurons that signal gene activation triggered by a later social fear experience (red).  Source: Fan Wang, Ph.D., Duke University

Grant

MH103908

Reference

Sakurai K, Zhao S, Takatoh J, Rodriquez E, Lu J, Leavitt AD Fu M, Han B-X, Wang F. Capturing and Manipulating Activated Neuronal Ensembles with CANE Delineates a Hypothalamic Social-Fear Circuit, Neuron, Volume 92, Issue 4, 23 November 2016, Pages 739–753.
http://dx.doi.org/10.1016/j.neuron.2016.10.015 

For more information, see:
New technology reveals social-fear circuit