Basic information

Investigator: prof. MUDr. Jiří Horáček, Ph.D.
Main recipient: Institute of Physiology of the Czech Academy of Sciences, v.v.i.
Co-recipient: National Institute of Mental Health (NIMH)
Research period: 1/5/2025 - 31/12/2028
Total budget: 6,751,000 CZK​​​​​​​
NIMH budget: 2,830,000 CZK​​​​​​​
Supported by: Czech Health Research Council (AZV ČR)

 

 

Annotation

Establishing reliable animal models for psychiatric disorders such as schizophrenia is essential for advancing our understanding of the neurobiological, behavioral, and genetic underpinnings of this condition. This study proposes that disrupted visual signal processing at the sensory periphery (retina) leads to unstable endogenous world models and aberrant perception of everyday reality, potentially contributing to the development of schizophrenia. We hypothesize that prolonged exposure to aberrant sensory signals induces unstable network connectivity in the prefrontal cortex and non-physiological pruning during the subadult period. To test this hypothesis, we will utilize a specially bred transgenic TH-Cre knockin rat line, subjected to viral transfection of designer receptors (DREADDs) on the retina during early subadult life. These receptors will be repeatedly activated to induce unpredictable sensory noise and fluctuations in retinal dopamine release. The animals will then undergo a series of behavioral and cognitive tests commonly used in animal models of schizophrenia in adulthood. Subsequently, magnetic resonance imaging (MRI) will be conducted to measure the volumetry of specific brain regions, particularly the prefrontal cortex, which is critical in the pathophysiology of schizophrenia. Additionally, histological analysis and spectral analysis of the vitreous body will be performed to verify the functionality of the viral transfection and fluctuations in retinal dopamine depletion.