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
Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland
Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
14.12.2018 | Power and Electrical Engineering
14.12.2018 | Physics and Astronomy
14.12.2018 | Physics and Astronomy