Journal Article

Switching on and off fear by distinct neuronal circuits

Demmou, Lynda, Ciocchi, Stephane, Lüthi, Andreas, Senn, Verena, Müller, Christian, Herry, Cyril

2008

Overview

Switching between exploratory and defensive behaviour is fundamental to survival of many animals, but how this transition is achieved by specific neuronal circuits is not known. Here, using the converse behavioural states of fear extinction and its context-dependent renewal as a model in mice, we show that bi-directional transitions between states of high and low fear are triggered by a rapid switch in the balance of activity between two distinct populations of basal amygdala neurons. These two populations are integrated into discrete neuronal circuits differentially connected with the hippocampus and the medial prefrontal cortex. Targeted and reversible neuronal inactivation of the basal amygdala prevents behavioural changes without affecting memory or expression of behaviour. Our findings indicate that switching between distinct behavioural states can be triggered by selective activation of specific neuronal circuits integrating sensory and contextual information. These observations provide a new framework for understanding context-dependent changes of fear behaviour. Tripping the 'fear switch' For many animals, an ability to switch from a 'normal' bold or exploratory approach to a situation to a more defensive approach when prudent is an important survival aid. Much is known about the role of entire brain areas in such processes, but what happens at the level of neuronal circuits is less well understood. 'Fear extinction' and 'renewal', two processes in which learned fearful responses to stimuli associated with unpleasant consequences are unlearned, then renewed, are effective models for probing mechanisms associated with changes in behavioural state. Herry et al . show that changes in the balance of activity of two distinct neuronal populations in the basolateral amygdala can trigger transitions between states of high and low fear in mice. Likhtik et al . report another mechanism for 'unlearning' fearful memories, this time in rats. Amygdala cells known as intercalated neurons, which receive information from the basolateral amygdala, appear to be responsible in this case. This work suggests possible new avenues for the treatment of anxiety disorders. Changes in the balance of activity of two distinct neuronal populations in the basolateral amygdala trigger transitions between states of high and low fear in mice. The two populations of neurons tend to participate in different anatomical circuits, suggesting that even within a single brain area, selective activation of specific neuronal circuits can trigger large changes in behavioral state.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Amygdala - cytology / Amygdala - physiology / Anatomical correlates of behavior / Animals / Behavioral psychophysiology / Biological and medical sciences / Conditioning (Psychology) / Control / Extinction, Psychological / Fear / Fear - physiology / Freezing Reaction, Cataleptic - drug effects / Freezing Reaction, Cataleptic - physiology / Fundamental and applied biological sciences. Psychology / Humanities and Social Sciences / Inactivation / Male / Mice / Mice, Inbred C57BL / Models, Animal / multidisciplinary / Muscimol - pharmacology / Neural Pathways / Neurons / Neurons - classification / Neurons - physiology / Psychological aspects / Psychology. Psychoanalysis. Psychiatry / Psychology. Psychophysiology / Science / Science (multidisciplinary) / Species extinction / Studies