Project Details
Projekt
Molecular and neuronal pathway-specific analysis of pathognomonic signatures in two-hit schizophrenia mouse models combining environmental and genetic risk factors
Subject Area
Biological Psychiatry
Term
from 2015 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 268620532
Increasing evidence suggest that disturbed functional connectivity across brain regions is implicated in the etiology of psychotic diseases, including schizophrenia (SZ) and bipolar disorders. Cognitive symptoms are a common hallmark of this heterogeneous group of diseases. The underlying mechanisms, however, remain still largely elusive. Human imaging data and studies in animal models suggest that impaired interactions of the ventral Hippocampus (vHi) and the medial prefrontal Cortex (mPFC) could be associated with cognitive deficits in SZ. In this proposal, we suggest to apply optophysiology on brain slices of neuron-type reporter mice in combination with molecular profiling techniques to characterize pathway-specific mechanisms underlying vHi-mPFC interactions. Therefore, we will make use of a well characterized mouse model for the SZ-risk gene TCF4 named Tcf4tg crossed with fluorescent reporter mice for endocannabinoid receptor-positive interneurons and parvalbumin-positive interneurons, in which cell-type specific optophysiological recordings and molecular profiling can be performed. We could previously show that Tcf4tg mice display several behavioral endophenotypes of Sz, including Hi dependent cognitive deficits and sensori-motor gating. In particular, cognitive deficits depending on the mPFC are amplified when Tcf4tg mice are subjected to psychosocial stress modeling gene x environment (GxE) interactions of SZ. If successful, we will identify the cellular and molecular substrates underlying disturbed vHi-mPFC connectivity in the Tcf4tg GxE model which would pave the way for follow-up studies in other models in the future.
DFG Programme
Research Grants
Major Instrumentation
Spot Illumination mit Kamera
Instrumentation Group
5080 Optisches Mikroskopzubehör
