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.
Using immunohistochemical methods and a series of transgenic mouse lines, the researchers succeeded in mapping the gene activity of the type 1 CRH receptor in the mouse brain in detail for the first time. Interestingly, a specific activity pattern emerged in different neuron groups which release different neuronal messenger substances. In regions of the forebrain (cortex, hippocampus, thalamus, septum), CRHR1 is detectable in glutamatergic and GABAergic neurons. As the limbic system, these regions are linked and, as the current study shows, trigger fear-inducing behaviour in glutamatergic neurons.
In regions of the midbrain (substantia nigra, ventral tegmental area), CRHR1 arises in dopamine-releasing neurons. The functional examination of the mice gave rise to the fairly sensational discovery that the stress hormone CRH actually reduces fear through its receptors in this part of the brain. These neurons demonstrably trigger the direct release of dopamine in regions of the forebrain and hence cause behaviour that overcomes fear.
The opposing effects of the fear-generating and fear-eliminating effect of the CRH/CRHR1 was demonstrated for the first time by this study and prompted the re-evaluation of the use of CRH-receptor antagonists as anxiolytic and antidepressant drugs. The authors speculate that the over-activity of the CRH system in patients with mood disorders is not general but probably limited to certain regulatory circuits in the brain, thus causing imbalanced emotional behaviour. “The use of CRH-receptor 1 antagonists could be particularly useful in patients in who one of these systems is out of sync,” says research group leader Jan Deussing.
Dr. Barbara Meyer | alfa
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News