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, email@example.com.
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, firstname.lastname@example.org
Dr. Anke Sauter | idw - Informationsdienst Wissenschaft
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy