German-American team of researchers finds neurophysiological correlates for cognitive and emotional symptoms in a Schizophrenia mouse model.
Schizophrenia is not only associated with positive symptoms such as hallucinations and delusions, but also with negative symptoms e.g. cognitive deficits and impairments of the emotional drive. Until now, the underlying mechanisms for these negative symptoms have not been well characterized.
In the current edition of the Proceedings of the National Academy of Sciences (PNAS) a German-American team of researchers, with the cooperation of the Goethe University, reports that a selective dopamine midbrain population that is crucial for emotional and cognitive processing shows reduced electrical in vivo activity in a disease mouse model.
Schizophrenia is a severe and incurable psychiatric illness, which affects approximately one percent of the world population. While acute psychotic states of the disease have been successfully treated with psychopharmaceutical drugs (antipsychotic agents) for many decades, cognitive deficits and impairments of motivation do not respond well to standard drug therapy.
This is a crucial problem, as the long-term prognosis of a patient is determined above all by the severity of these negative symptoms. Therefore, the shortened average life-span of about 25 years for schizophrenia patients remained largely unaltered in recent decades.
"In order to develop new therapy strategies we need an improved neurobiological understanding of the negative symptoms of schizophrenia" explains Prof. Roeper of the Institute for Neurophysiology of the Goethe University. His American colleagues, Prof. Eleanor Simpson and Prof. Eric Kandel at Columbia University in New York recently made an important initial step in this direction.
They created a new transgenic mouse model based on striatal overexpression of dopamine typ 2 receptors, which displayed typical signs of cognitive and emotional negative symptoms similar to those occurring in patients with schizophrenia. The researchers detected typical impairment in working memory with corresponding neurochemical changes in dopamine in the prefrontal cortex. However, the underlying neurophysiological impairments of dopamine neurons remained unresolved.
Now, Prof. Eleanor Simpson and Prof. Jochen Roeper, in cooperation with the mathematician Prof. Gaby Schneider of the Goethe University and the physiologist Prof. Birgit Liss of the University of Ulm have succeeded in defining the neurophysiological impairments with the dopamine system. They were able to show, with single cell recordings in the intact brain of mice, that those dopamine midbrain neurons responsible for emotional and cognitive processing displayed altered patterns and frequencies of electrical activity. In contrast, adjacent dopamine neurons, which are involved in motor control, were not affected.
The researchers were also able to show that – in line with the persistence of cognitive deficits in mice and patients– the pathological discharge patterns of dopamine neurons persisted even after the causal transgene had been switched off in adult mice. "This result emphasizes the presence of a critical early phase for the development of cognitive deficits in schizophrenia" according to Roeper. He and his colleagues are currently examining how the neuronal activity of dopamine neurons changes during the working memory tasks. "Our results show that altered neuronal activity of selective dopamine neurons is crucial for schizophrenia", Jochen Roeper summarises the importance of the research work.
Krabbe et al.: Increased dopamine D2 receptor activity in the striatum alters the firing pattern of dopamine neurons in the ventral tegmental area, in PNAS 9.2.2015, www.pnas.org/cgi/doi/10.1073/pnas.1500450112
Information: Prof. Jochen Roeper, Institute for Neurophysiology, Campus Niederrad, Tel.: +49 (0)69 6301-84091, firstname.lastname@example.org.
Goethe University is a research-oriented university in the European financial centre Frankfurt Founded in 1914 with purely private funds by liberally-oriented Frankfurt citizens, it is dedicated to research and education under the motto "Science for Society" and to this day continues to function as a "citizens’ university". Many of the early benefactors were Jewish. Over the past 100 years, Goethe University has done pioneering work in the social and sociological sciences, chemistry, quantum physics, brain research and labour law. It gained a unique level of autonomy on 1 January 2008 by returning to its historic roots as a privately funded university. Today, it is among the top ten in external funding and among the top three largest universities in Germany, with three clusters of excellence in medicine, life sciences and the humanities.
Publisher The President of Goethe University, Marketing and Communications Department, 60629 Frankfurt am Main
Editor: Dr. Anne Hardy, Officer of Science Communication, Tel: +49(0)69 798-12498, Fax +49(0)69 798-761 12531, email@example.com
Dr. Anke Sauter | idw - Informationsdienst Wissenschaft
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy