Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - PSYCHOCELL (Cellular substrate of abnormal network maturation in neuropsychiatric disorders)

Teaser

The long-lasting burden of major neuropsychiatric disorders, such as schizophrenia, results from disruption of cognitive performance in daily life. Impairment of long-range communication between two brain regions, the prefrontal cortex and hippocampus, represents the substrate...

Summary

The long-lasting burden of major neuropsychiatric disorders, such as schizophrenia, results from disruption of cognitive performance in daily life. Impairment of long-range communication between two brain regions, the prefrontal cortex and hippocampus, represents the substrate of disease-specific mnemonic and executive deficits. While it has been hypothesized that this impairment emerges long before the first clinical symptoms, technical and ethical limitations of non-invasive investigations in high-risk infants precluded the elucidation of ontogenetic mechanisms underlying the pathophysiology of disease. Using mouse models of disease’s etiology, we recently identified the de-coupling of prefrontal-hippocampal networks during early development as potential mechanism underlying adult circuit dysfunction. However, it is still unknown, which neuronal populations are particularly affected and critically contribute to the disease-related defects of long-range communication in the brain. The proposal aims to identify the developmental processes by which distinct cellular elements contribute to dysfunction and poorer cognitive performance in schizophrenia.

Work performed

The project led already to major knowledge gain summarized as following:

• Identification of a neuronal subpopulation in the prefrontal cortex as key players controlling the miswiring of neuronal networks during early development in mouse models of mental illness;
• Resolving of mechanisms underlying the abnormal long-range communication in the developing brain of mouse models of schizophrenia
• Evidence that the early oscillatory activity is necessary for the development of cortical circuits, their adult function and cognitive performance
• Methodological advancement: establishment of a new protocol for manipulation of developing neuronal networks

Final results

We are currently investigating whether other neuronal populations are also critically involved in the dysfunction and behavioral deficits related to schizophrenia. Understanding the cellular mechanisms of dysfunction during early development may open new therapeutic perspectives that, when initiated before the onset of clinical symptoms, may improve the devastating outcome of disease.

Website & more info

More info: http://www.opatzlab.com.