Fear ‘off switch’ in mouse brains could lead to new treat­ments for anxiety dis­or­ders

Focus-Science and Technology - - DISCOVERIES -

Faced with a po­ten­tial threat, a mouse will re­spond in one of three ways: ei­ther freez­ing (mak­ing it harder for the preda­tor to de­tect it), duck­ing into the near­est shel­ter, or run­ning for its life. Now, a team at Stan­ford Univer­sity School of Medicine has iden­ti­fied two clus­ters of nerve cells in a mouse’s brain that con­trol this re­sponse by send­ing sig­nals to dif­fer­ent re­gions. As sim­i­lar cir­cuitry is found in hu­man brains, the discovery could po­ten­tially lead to new ways of treat­ing pho­bias, anxiety dis­or­ders and post-trau­matic stress dis­or­der, they say.

The re­searchers placed mice into a spe­cially de­signed tank that sim­u­lated the ap­proach of a bird of prey by dis­play­ing an ex­pand­ing dark disc above the mice’s heads, rep­re­sent­ing the shadow of a preda­tor as it swooped over­head. By mon­i­tor­ing the mice’s brain ac­tiv­ity as the ‘preda­tor’ at­tacked, the re­searchers were able to de­ter­mine that the ven­tral mid­line thal­a­mus, or vMT, fired ev­ery time the mice sensed they were in dan­ger. They then traced out­puts from the vMT to the ba­so­lat­eral amyg­dala and the me­dial pre­frontal cor­tex. Pre­vi­ous work has shown that the amyg­dala is in­volved with the pro­cess­ing of threat de­tec­tion and fear, and the me­dial pre­frontal cor­tex is as­so­ci­ated with high-level cog­ni­tive con­trol and anxiety.

They found that stim­u­lat­ing the amyg­dala in­creased the like­li­hood that the mice froze, while stim­u­lat­ing the me­dial pre­frontal cor­tex led the mice to stand their ground and act in an un­char­ac­ter­is­ti­cally brave man­ner.

“You could hear their tails thump­ing against the side of the cham­ber,” said lead re­searcher Dr An­drew Hu­ber­man. “It’s the mouse equiv­a­lent of slap­ping and beat­ing your chest and say­ing, ‘Okay, let’s fight!’.”

As hu­man brains have a struc­ture sim­i­lar to the vMT, Hu­ber­man sus­pects that peo­ple with pho­bias, con­stant anxiety or PTSD, mal­func­tion­ing cir­cuitry or trau­matic episodes may ben­e­fit from ther­a­pies de­signed to damp down sig­nalling in the re­gion.

“This opens the door to fu­ture work on how to shift us from paral­y­sis and fear to be­ing able to con­front chal­lenges in ways that make our lives bet­ter,” said Hu­ber­man.

Stim­u­lat­ing a par­tic­u­lar re­gion in a mouse’s brain will make it stand its ground when faced with a preda­tor

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