How does fear freezes us?

Midbrain circuits for defensive behaviour.
Tovote P, Esposito MS, Botta P, Chaudun F, Fadok JP, Markovic M, Wolff SB, Ramakrishnan C, Fenno L, Deisseroth K, Herry C, Arber S, Lüthi A, Friedrich Miescher
Nature. 2016 Jun 1;534(7606):206-12. doi: 10.1038/nature17996.
Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland.
INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, Bordeaux 33077, France. Stanford University, 318 Campus Drive West, Clark Center W080, Stanford, California 94305, USA. Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.

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In a collaborative study involving the group of Andreas Lüthi and Silvia Arber at the Friedrich Miescher Institute for Biomedical Research (FMI) in Basel, Switzerland and the group of Cyril Herry at the Neurocenter Magendie in Bordeaux, France, the neuronal circuits in the brain which control defensive behavior in threatening situations have been identified. In a study published in Nature, the authors show which neurons trigger fear-related freezing and how the freezing pathway interacts with pathways responsible for flight.

Fear protects us in a world full of dangers. This is particularly evident in small rodents, such as mice, which exhibit various reactions to threats: freezing, flight or – as a last resort – defensive attack. In recent decades, researchers have investigated the processes in the brain, which give rise to fear, and how fear is learned. But it has not been clear to date how the state of fear triggers a response, which extends all the way to the muscles.

Using modern neuroanatomical tracing methods in combination with physiological approaches, the researchers identified neurons in the midbrain that are activated during freezing. They then identified an output pathway leading to a medullary area involved in motor control. At the same time, they identified a pathway leading from the central nucleus of the amygdala (the forebrain structure controlling fear responses) to the midbrain. These findings defined the neuronal circuitry underlying the execution of freezing, from the central nucleus of the amygdala to the neurons that control our muscles. Often, the behavioral response to a threat needs to be rapidly adapted; for example, there may be a switch from freezing to flight. The researchers therefore investigated whether and how freezing is influenced by the flight pathway. The authors find evidence that the circuit that triggers freezing interacts with the flight circuit at the anatomical and functional level.

Evolutionarily conserved strategies for coping with fear – essential for survival – are deployed by a wide variety of species. Similar mechanisms exist in humans and it is conceivable that malfunction of the circuitry identified plays also a role in people suffering from anxiety disorders.

*Fabrice Chaudun en 3ème année de thèse chez Cyril Herry , titre de sa thèse: Implication des voies de projection du cortex préfrontal dorso-médian vers l’amygdale et la substance grise periaqueductale dans l’expression des réponses conditionnés de peur . Soutenance le Mardi 16 Septembre 2016