Control of fear in the brain decoded

When healthy people are faced with threatening situations, they react with a suitable behavioural response and do not descend into a state of either panic or indifference, as is the case, for example, with patients who suffer from anxiety.

With the help of genetic studies on mice, scientists from the Max Planck Institute of Psychiatry have discovered two opposing neuronal regulatory circuits for the generation and elimination of fear. Both are controlled by the stress-inducing messenger substance corticotropin-releasing hormone (CRH) and its type 1 receptor (CRHR1). The availability of these factors in neurons that release glutamate in brain areas of the limbic system activates a neuronal network which causes anxiety behaviour.

Conversely, in dopamine-releasing neurons in the mid-brain, these factors give rise to behaviour that reduces fear. Because disorders of the stress factors may be observed in many patients with affective illnesses, the scientists suspect that the pathological alteration of the CRHR1-dependent regulatory circuits may be at the root of such emotional maladies.
 
An organism's response to stress is one of the key strategies essential to its survival in dealing with environmental factors. A balanced emotional reaction is of particular importance here and is subject to a highly complex molecular regulation system.

Corticotropin-releasing hormone (CRH), which is released in the brain and places the organism in a state of alert, is a central molecular factor of the stress response. In addition to its effect as a hormonal messenger substance, it also controls the activity of neurons through binding to its receptors.

Many patients with anxiety disorders and depression display an altered hormonal stress response and have increased volumes of CRH in the brain. To investigate the underlying pathological processes, the research team working with Jan Deussing at the Max Planck Institute of Psychiatry carried out studies on the mouse model system.

This enabled them to selectively deactivate an important factor, for example the CRH type 1 receptor, in certain cells, and thus establish the locations where the receptor is normally active and identify its function.